CDP B - Lualhati, Anna Lourdes (1) - NoRestriction

For exclusive use of Lualhati, Anna Lourdes
PART B
Fresenius Medical Care Asia Pacific
CDPB112013
INTRODUCTION This course provides an update on the current trends in Renal Replacement Therapies, as well as ensuring that the RN has a sound foundation in understanding of the principles underpinning RRT. This ensures that the RN has effective, flexible knowledge in order to deliver, adjust and evaluate care. The scope of this course includes CKD, dialysis and its application to practice, pharmacology, Fluid assessment and management, EBP and Clinical Practice Guidelines, vascular access management, clinical assessment and nutritional management of the chronic hemodialysis patient population. Sound clinical decision-making is based on theoretical understanding, so for the Nephrology/Dialysis nurse it is paramount to have this knowledge that is flexible to adapt and deal with the myriad of complex issues in the chronic dialysis therapy. Profile of ESRD population: Chronic care management of persons with ESRD has been available for more than 40 years. With increasing incidence and prevalence of ESRD (Access the websites below) there is increased demand for RRT service. The incidence rate is highest in Taiwan, with the Mexico second, followed by USA and Japan. Also of significance is that Diabetes has a strong association with the renal etiology or as co-morbidity (Malaysia has the highest incidence of Diabetic Nephropathy globally). Thereby the challenge for renal professionals includes: 1. Increasing ESRD population requiring RRT 2. Increasing numbers of patients with co-morbidities (e.g. Diabetes) 3. Further an aging of the ESRD population. These factors contribute to increases in patient hospitalizations, adverse events during dialysis and mortality of the ESRD population, posing many challenges for nurses in the field of Nephrology care. The Role of the Dialysis Nurse is a reflection of the needs of the dialysis population as well as the professional expectations. The professional bodies out line these expectations (e.g. RENAP, ANNA) and include means of determining knowledge (courses, examinations), clinical competencies and the relationship between the Medical and nursing teams in order to deliver best outcomes for the dialysis population. http://www.usrds.org/adr.htm http://www.anzdata.org.au/ http://www.anzdata.org.au/anzdata/AnzdataReport/ 28thReport/files/Ch04Dialysis.pdf USA Renal registry Australia and NZ Renal Registry Summary of Dialysis profile in Australia/NZ
You may also find the following websites useful to access both for this segment of the course and for the Program overall. I would suggest adding them to your Favorites or Bookmark: -
CDPB112013
DOPPS (Dialysis Outcomes Practice Patterns Study): Hypertension Dialysis and Clinical Nephrology: International Society of Nephrology:
www.dopps.org www.hdcn.org www.isn-online.org
Renal Replacement Therapies (RRTs) ability to actually replace renal function is incomplete, to varying degrees. These limitations afford the opportunity for pharmacological and alternative therapies to supplement the dialysis and transplant modalities that incorporate the RRTs.
What is the Aim of Renal replacement therapy? The Aim is to replace (and in some cases restore) renal function by Dialysis. However there are many functions of the renal system including: Fluid and electrolyte homeostasis Acid-base balance Blood pressure control (in part through Renin release from the Juxta-Glomerular Apparatus) Vitamin D hydroxylation Release of Erythropoeitin and maintenance of hemoglobin. The achievement of these functions is through Filtration, secretion, reabsorption/absorption and excretion. However some of these functions are not achieved by dialysis; Vitamin D hydroxylation and Erythropoietin production and release. Please complete the Renal Anatomy and Physiology section as we present the information in class. The session highlights the intricacy of renal function together with the dependence on renal function for maintenance of normal cellular function and life.
CHANGING PARADIGM OF PRACTICE IN RRT CHANGING PRADIGM OF PRACTICE IN RRT The challenges in RRT practice have been identified. The challenges posed offer an opportunity to refocus on the critical components that contribute to a greater likelihood of increased well-being and quality of the life gained, for individuals with ESRD. This does not mean discarding our current practices, but using this knowledge and practices to answer more effectively the needs of ESRD clients in the short and long-term. It also means becoming more clients centric. Using this framework, we are able to work towards balancing the science with the psychosocial needs of the client. In partnership with the clients we are also able to continuously refine/adjust the prescription of care, and motivate active participation with their disease management.
CDPB112013
Thereby rather than just focusing on the quantification, these measures now are tools to achieve and then further measure the degree of recovery/improvement that occurs with that dose or prescription of therapy. We will now discuss the pathophysiology of CKD and its impact on the individual physiologically and psychologically.
HOMEOSTATIC MECHANISMS 1. Kidneys The kidneys are vital for fluid and electrolyte balance in the body. The kidneys normally filter approximately 170-180 liters of filtrate per day (Glomerular Filtration Rate (GFR)), which enables the body to continuously check and titrate / adjust the physiological needs of the body. A human only excrete 1.5 to 2.0 liters per day of urine, and reflects the energy required by the kidneys to reabsorb approximately 99% of the fluid that it has filtered. Although the kidneys respond autonomously to concentration gradients and other physiologic stimuli, they are also responsive to hormones like Aldosterone (sodium retaining), ADH (Anti diuretic hormone) and Renin (Renin Angiotensin-aldosterone system R-A-A-S) that maintains blood pressure, GFR and thirst. The kidneys are responsible for the following: a. Regulation of ECF volume and electrolytes: ADH, RAAS, Aldosterone, Atrial Naturietic Factor. b. Regulation of electrolytes in ECF by selective retention and/or secretion (excretion) c. Regulation of pH by excretion of hydrogen ions and reclamation (absorption) of d. Bicarbonate: Carbonic Anhydrase is an enzyme utilized in this process located in the renal tubule (proximal and distal convoluted segments). e. Excretion of metabolic wastes: protein metabolites, cellular wastes, drug metabolites and other toxic substances. In clients with renal dysfunction these processes are compromised with resultant fluid and electrolyte imbalance, which contributes to some of the clinical manifestations associated with renal failure. Fresenius Medical Care Asia Pacific
CDPB112013
Q. Think about your clients in the Dialysis Centre and their clinical manifestations, how are they related to fluid and electrolyte imbalance? 2. Lungs The lungs are involved in pH homeostasis through the elimination of excess hydrogen ions. The lungs under the influence of the medulla act promptly to correct derangements in acid-base balance by regulating the carbon dioxide level (potential weak acid Carbonic acid) in the ECF. The kidneys and lungs work together to maintain the ECF pH of between 7.35 - 7.45, which is critical for normal cellular activities. 3. Pituitary Gland The hypothalamus produces the Anti Diuretic hormone, which is then stored in the posterior pituitary gland. This hormone is released in response to ECF osmolarity and pressure receptors, located in the atria of the heart and blood vessels. The release of the ADH is more sensitive to changes in ECF (plasma) osmolarity. The ADH changes the permeability of the late segment of the distal convoluted tubule and the collecting duct of the nephrons. Fluid then fluxes across the more permeable membrane because of an osmotic gradient across the membrane (between the interstitial and tubular fluid). The result of ADH secretion is reduced urinary output and fluid retention. 4. Adrenal Glands Adrenal glands secrete Aldosterone from the adrenal cortex. This hormone increases sodium reabsorption form the distal tubule of the nephrons in exchange for increased potassium secretion and excretion. The result of Aldosterone secretion is sodium retention, lowering of plasma potassium and fluid retention as a result of sodium reabsorption. The regulators of Aldosterone secretion include sodium and potassium concentration, and Angiotension II (the result of Renin secretion) that is the primary regulator of Aldosterone secretion. 5. Parathyroid Glands The parathyroid glands (PG) secrete intact Parathyroid Hormone (iPTH) which increases osteoclast activity that increases the resorption of calcium and phosphate form the bone. The PG is sensitive to the ionized calcium (free unbound calcium) in the blood and its role is to increase the plasma level of calcium, primarily through resorption of bone analytes. The iPTH also increases phosphate excretion across the nephrons tubule. The PG is controlled not only by ionized calcium levels but also by Vitamin D (active vitamin D; I, 25 Dihydroxycholecalciferol) which acts as negative feedback to iPTH secretion.
CDPB112013
ROLE OF MAJOR ELECTROLYTES 1. SODIUM Sodium is major ECF cation and provides osmolarity to body fluids. Serum sodium level relates closely to the fluid status of the client. When evaluating the biochemical serum sodium value, the nurse should always evaluate the fluid status through physical examination. The serum sodium, because it is the major ECF cation is prone to hemodilution, meaning that if the client has a large ECF volume there will be dilution of those ions and analytes found predominantly in the ECF (Sodium, Hemoglobin, Albumin). If the client is volume depleted these same analytes can be hemoconcentrated. For every 3 Mm of serum sodium rise above the normal range, equates to approximately 1 liter deficit of body water. Elevated BSL (Blood Glucose Level) attracts fluid from the cells into the ECF; dilutes the plasma Sodium. Every 3-4 Mm/L increment increase in plasma glucose causes fluid to move out of the cells and dilute the plasma sodium by 1 Mm/L. This effect may not be observed as the increase in fluid shift results normally in increased diuresis. Q. Analyze your clients last blood result and look at their Sodium, BSL (if diabetic) and correlate these parameters with the fluid status. How was their fluid volume implicated in the biochemistry? 2. POTASSIUM Potassium is the major intracellular cation and is not influenced by changes in fluid status in the ECF. The body stores the potassium within the cells; therefore the ECF potassium level is only a reflection of total body potassium level. Potassium control is a function of the kidney and adrenal gland. Hyperkalemia occurs when there is renal impairment and if there is deficiency of, or interference with the action of Aldosterone. Potassium levels in the ECF are affected by cell destruction/resolution e.g. cell destruction and damage results in the liberation of potassium thereby increasing the plasma (ECF) level of potassium. Artefactual causes can result in derangements of potassium and include: A hemolyzed sample An old blood sample A sample of cooled blood prior to separation (spinning of blood) Contamination with K.EDTA Contribution from very high platelet or white cell counts.
Alterations in acid-base balance also significantly affect plasma potassium levels. Acidosis results in a shift of potassium from the cell, increasing the ECF potassium. Alkalosis results in a shift of potassium into the cell, thereby decreasing the serum level. On average for every 0.1 unit change in arterial pH there is a reciprocal change in 0.5 Mm/L of plasma potassium. Insulin promotes cell entry of ECF potassium, temporarily lowering the serum potassium level.
CDPB112013
Q. What is the role and function of potassium in human physiology? Analyze your clients potassium level pre-dialysis and their bicarbonate level. Does their potassium level change with their acid-base status? 3. BICARBONATE The plasma bicarbonate level is the most practical index of the degree of acidosis in ESRD clients. A low bicarbonate level may be due to: Accumulation of acid anions in the blood, buffered by bicarbonate, resulting in a lower bicarbonate level due to the consumption of this buffer during the process. Metabolic processes generate approximately 60 Mm of Hydrogen ions per day, which can be increased it client is catabolic ( rate of hydrogen ion production) or has a high protein intake. Failure to replace enough bicarbonate consumed in physiologic processes, during the dialysis procedure. 4. CALCIUM Calcium is absorbed from the gut under the influence of active Vitamin D (1, 25 Dihydroxycholecalciferol). Calcium is important for normal musculo-skeletal function, cardiac conduction, neurological conduction and function and blood vessel dynamics. Total calcium in plasma is the sum of the ionized (free, unbound calcium; 47%) and the nonionized (53%) calcium components. The nonionized portion consists of calcium bound to albumin (40%) and that chelated to anions like Phosphate and citrate (13%). To evaluate the actual calcium level, need to know the serum albumin level and apply the following: Serum calcium may be corrected for variations in albumin by estimating that a change in serum albumin of 10g/L will change the total serum calcium by 0.8 mg/dL (0.2 Mm/L). The binding between calcium and albumin is also affected by pH. Alkalosis increases the binding of calcium to albumin. Other factors that can acutely lower the ionized calcium levels are for example, increased levels of lactate, bicarbonate and phosphates.
5. PHOSPHATE Phosphate is found in the phospholipid membranes of cells. Thereby any cellular destruction will result in a factitious high phosphates level in the plasma. Phosphate levels are evaluated in relation to the calcium since there is an inverse relationship between the 2 analytes (e.g. an increased phosphate level results in a lower ionized calcium level, as the free ionized calcium binds with the free phosphate). Like potassium, phosphate moves into the cell with insulin secretion. Phosphate levels in plasma of clients with ESRD can also be raised because of reduced renal clearance and protein intake (phosphate load). In ESRD clients, maintenance of serum phosphate remains difficult and is poorly managed by dialysis as most phosphate is located intracellular and takes time to move to the ECF compartment for clearance. Management includes diet modification and pharmacological agents.
CDPB112013
BIOCHEMISTRY & PATHOLOGY IN ADVANCED PRACTICE Biochemical analysis forms a major component of evaluating the effectiveness of the RRT. Normal kidney function maintains fluid and electrolyte homeostasis, thereby part of the RRT role is to replace this function with biochemical analysis forming a component of the outcome measurement. Importantly when analyzing the biochemistry the blood is representative of the total body balance per electrolyte under analysis. Therefore accurate sampling of blood is critical for effective analysis, interpretation and care planning.
Body compartments
Lymphatic system
Vascular Space (5 Litres)

Capillary membrane interface
Interstitial Space (10 Litres)
Intracellular Space (25 Litres)
Cell membrane interface
Extracellular space
Intracellular space
The major extracellular cation is Sodium, with Potassium, Calcium and Magnesium contributing to the extracellular cation pool. About 90% of the ECF osmolarity is determined by the sodium concentration. The sodium value can be diluted by changes in blood sugar value and protein values that also are osmotic agents and in ESRD patients with fluid excess. The major intracellular cation is Potassium, with Magnesium and Sodium completing the total cation pool. The major extracellular anion is Chloride (found usually as Sodium Chloride), and Bicarbonate, phosphate, sulfate organic acids and proteinates. The intracellular anions are predominately the phosphates and sulfates, with Bicarbonate and proteinates further contributing to the negative charge pool.
WHEN ANALYZING THE FOLLOWING ELECTROLYTES CONSIDER THE FOLLOWING: Sodium CLOSELY RELATED TO FLUID STATUS. For approximately 3 Mm increase in Sodium above normal range = deficit of approximately 1L (Adults) BGL increase and Hyperlipidaemia both artificially reduce the Serum Sodium value by dilution because of the osmotic pull of fluid from intracellular and interstitial fluid spaces. Fresenius Medical Care Asia Pacific
CDPB112013
Potassium ALTERATIONS IN ACID-BASE BALANCE significantly affect potassium distribution. Acidosis shifts potassium from the cell, increasing the serum Potassium and Alkalosis results in a decrease in Serum Potassium. For every 0.1 unit change in arterial pH results in a reciprocal change of 0.5 Mm/L in serum Potassium level. Insulin promotes Potassium movement into the cell and temporarily lowers the serum Potassium. Hemolysis, Leukocytosis and increased platelet counts can cause raised serum Potassium levels, through the release of intracellular Potassium into the plasma. Bicarbonate Often represented as Carbon Dioxide content (Total bicarbonate and carbonic acid in venous blood) represents the consumption and generation of buffer, thereby reflecting the acid-base needs, consumption, production and utilization of buffer. Phosphate - Like potassium, because it is found predominately intracellularly, can be artificially raised when cells are hemolyzed. Phosphate levels are evaluated in relation with calcium, as there is an inverse relationship between the 2 parameters; raised phosphate will lower the calcium level (significantly the ionized calcium this is important for ESRD population as will further stimulate the Parathyroid gland (PG) to release iPTH). Insulin promotes the movement of extracellular phosphate into the cell, thereby temporarily lowering the serum phosphate level. Cell recovery will utilize > amounts of phosphate and present a lower serum phosphate. Calcium - TOTAL CALCIUM = OF IONISED (47%) AND NONIONISED CALCIUM (53%). The nonionised calcium = 40% bound to albumin and approximately 13% chelated to anions. Total calcium can be corrected for variations in serum Albumin; a 10g/L change in albumin will change the total serum calcium level by approximately 0.2 Mm/L. This needs to be modified with variations in pH; Alkalosis increases the binding of calcium to albumin thereby lowering the ionized calcium. Raised serum Phosphate or Bicarbonate levels also lower the calcium value. Creatinine - INDICATOR OF RENAL DISEASE Trend analysis of serum Creatinine is probably more important than a single result. Reflects the body muscle mass as Creatinine s generated from creatine phosphate; if individual has large muscle mass they will generate > amount and have a higher normal as opposed to an elderly person with reduced muscle mass may have a lower normal. Thereby assessment over time is paramount. Also used to assess muscle mass status based on trend analysis
CDPB112013
10
Urea - Urea is the end-product of cellular and protein degradation and metabolic processes. Raised serum Urea reflects one or more of the following: Increased catabolism; starvation, trauma, bleeding into the gut, or catabolic drugs (Prednisolone will increase the serum urea level unrelated to protein intake) Relates to exogenous protein intake Also reduced renal function (GFR) will result in an increased serum Urea. An increase in ADH (Antidiuretic Hormone) will also result in a raised serum Urea > than the rate of increase in the serum Creatinine. Albumin - Decreased serum Albumin will reduce the colloidal osmotic pressure in the intravascular compartment, resulting in the presence clinically of edema > than the fluid imbalance. The half-life of Albumin is approximately three weeks, often representing a disparity between the biochemical analysis and clinical presentation. Often this parameter is used for nutrition assessment but is not considered to be a major determinant of nutrition assessment. A lower serum Albumin may occur in conjunction with a raised Serum Ferritin (more specially CReactive Protein) reflecting an inflammatory condition and consumption of proteins in the process. Albumin like sodium is prone to dilution effects lower levels noted in fluid excess, with fluid removal albumin level increased until redistribution of fluid occurs across the compartments. Critical balance of electrolytes and osmolarity is required for normal cellular and enzymatic functions and actions.
PRINCIPLES & PRACTICE IN READING BIOCHEMISTRY REPORTS Always read biochemistry together with your physical assessment of the client Assess the biochemical parameter (analyte) over time. i.e. trend analysis. Never look at one result in isolation. Determine if any analyte may be causing misleading result. For example if BSL raised then it will lead to hemodilution of other major intravascular analytes. Determine if the analyte outside of target range is reflected by clinical state or by error in sampling of specimen and/or storage of specimen.
CDPB112013
11
A Framework for evaluation of biochemistry, including the importance of reviewing the patient together with the biochemistry, rather than in isolation. FRAMEWORK FOR ANALYZING BLOOD PATHOLOGY FOR ESRD POPULATION PARAMETERS Urea SpKt/V URR ANALYSIS Urea pre dialysis can indicate level of nutrition and adequacy of dialysis; generation of urea from last dialysis. spKt/V and URR analyze the adequacy of dialysis / clearance of solute. Hemoglobin is the indicator for management of anemia. TS% - Measure of plasma circulating iron relative to total iron-binding capacity. Transferrin is the plasma protein that transports iron. Ferritin reflects the stored iron; unless Ferritin levels are > 100 ng/mL response to EPO will be < effective and of short duration. Levels are kept > than this through iron infusions. TCO2 the consumption of buffer/ available buffer in the body; high protein intake, catabolic state or inadequate dialysis in result in low TCO2 levels. May also be complicated further if patient had chronic lung disease and / or id fluid overloaded unable to provide some respiratory compensation. Potassium deviations reflect either body losses/gains or redistribution within the body. Hypokalemia may be related with reduce intake, or increased losses (diarrhea, vomiting, RTA, diuretics, IV fluid without (Potassium replacement). Redistribution of potassium with alkalosis = Hypokalemia. Hyperkalemia results from reduced renal excretion, intake > output, cell damage/trauma = Hyperkalemia. In acidosis potassium moves from the cell to the plasma = Hyperkalemia.
A. ADEQUACY OF DIALYSIS
B. ANAEMIA
Hb TS% Ferritin
C. ACID BASE BALANCE
TCO2 Potassium Sodium
CDPB112013
12
D. NUTRITION
nPNA Albumin TCO2 Pre Urea Phosphate
When analyzing for nutritional status need to evaluate the nPNA which protein intake (grams/Kg/day). Intake can be broadly measured by Albumin, Pre dialysis Urea and phosphate. Analyze the similarity of the parameters and determine whether related to dialysis adequacy or nutrition. TCO2 may be lowered due to high intake of protein (related to nutrition) other factors for a low level have been discussed previously. Calcium and phosphate are both actively involved in bone mineralization. Calcium also has a role in cardiac conduction and clotting and muscle contraction. When phosphate levels are raised the free ionized calcium tends to bind with the excess phosphate. PG is sensitive to ionized calcium, therefore as it falls, PTH is released, and increasing the ionized calcium. This is unless the phosphate level remains raised, then the released calcium is taken up by the phosphate. Calcium phosphate product reflects the degree of metastatic calcification, due to high levels of phosphate binding the ionized calcium and depositing as complexes outside of bone.
E. BONE MANAGEMENT
Calcium ionized Calcium Phosphate Calcium x Phosphate IPTH Alkaline Phosphatase (ALP)
The analysis of the patients biochemistry provides the opportunity for a more focused clinical examination and history taking, but should never replace the need for a clinical assessment. In a latter section there are some Clinical Case studies for you to analyze using this framework. Also provided is a Conversion table that includes ESRD targets for most of the parameters. These have been based on the CPGs (KDOQI and CARI)
CDPB112013
13
LABORATORY VALUES /TARGTES FOR ESRD POPULATION (GUIDELINES) BLOOD CHEMISTRY ALBUMIN CONVERSION FORMULAE g/L 10 = g/dL ACCEPTABLE ESRD VALUES 40 g/L 35 125 U/L >4.0 < 9.0 mmol/L< 180mg/dL 8.810.8 mg/dL < 60 ( mg2/dL2) < 4.8 (mmol/L) VARIABLE ON BODY MASS & SEX VARIABLE ON BODY MASS & SEX 100 < 800 ng/mL or ug/L M/F : 1112 g/dL M/F :33 36 % 68% 50 ug/dL 5 = umol/L mmol/L = mEq/L mg/dL x 0.33 = mmol/L Pm/L F : 49 151 ug/dL M : 53 167 ug/dL 0.7 0.95 mmol/L 3.5 5.5 mmol/L < 5.5 mg/dL 15 30 pm/L 5 40 U/L 5 40 U/L mmol/L = mEq/L IRON TIBC = TS % mmol/L = mEq/L 135 149 mmol/L 20 55 % >20 < 24 mmol/L (Pre dx ) 280 400 ug/dL >120 < 240 mg/dL (>20 < 40 mmol/L) >70-75 % reduction 2.5 8.0 mg/dL
ALK PHOSHATE L = U/L (ALP)(SAP) BLOOD GLUCOSE LEVEL mg/dL 18 = mmol/L CALCIUM mg/dL 4 = mmol/L
CALCIUM PHOSPHATE PRODUCT CREATININE ( Pre-dx ) Mg/dL x 88.4 = mmol/L CREATININE (post-dx ) FERRITIN HAEMOGLOBIN/HEMATRO CIT HBA1C HEPATITIS B ANTIGEN IRON MAGNESIUM POTASSIUM PHOSHATE (INORGANIC) IPTH SGPT (ALT) SGOT (AST ) SODIUM TRANSFERRIN SATURATION TOTAL CO2 ( HCO3) TOTAL IRON CAPACITY UREA (pre-dx ) UREA (post_dx ) URATE Mg/dL x 88.4 = mmol/L ug/dL = ngm/L HCT % 3 = Hb g/dL
BINDING ug/dL 5 = umol/L Mg/dL 6 = mmol/L Mg/dL 6 = mmol/ Mg/dL 0.06 = mmol/
CDPB112013
14
BODY SYSTEM ALTERATIONS IN CKD IMPACT OF CKD AND UREMIA The impact of CKD on the body and individual is significant; ultimately affecting every body system together with the Chronicity of the disease contributing negatively to their perceived health related quality of life. The Figure 1.5.1.1 illustrates this impact on the individual. The progressive loss of renal function occurs over months to years, with patients usually presenting late in the disease process (due to minimal overt symptoms) with reduced opportunity to control and delay the progression to ESRD. In fact CKD has a classical natural history, availing an opportunity for intervention at secondary and tertiary prevention levels. See Figure 1.5.1.2.
Peripheral Neuropathy Paresthesias Motor weakness
Every body system is affected in CKD with the major impact (morbidity and mortality) on the cardiovascular system. This is not just as a consequence of fluid imbalance and the RAAS imbalance but the involvement of an inflammatory state now recognized as co-existent with CKD and will be discussed related to uremic toxins and the pathophysiology of CKD. Other important body system alternations include anemia, metabolic bone disease, and malnutrition. Fresenius Medical Care Asia Pacific
CDPB112013
15
KDOQI NKF STRATEGY FOR STAGING CKD
Primary Prevention: Secondary Prevention Screening Delay the progression Strategies to slow the progression of the disease:
Tertiary Prevention: reducing the complications
Management of uremic symptoms Prevention or correction of co-morbid conditions e.g. cardiovascular risk factors and correcting the anemia. Psychological and physical preparation for RRT Scheduled, timely initiation of RRT TREATMENT TO SLOW PROGRESSION OF CKD
100%
Treatment
% of kidnet function
50%
A A treated
0% 0 1 2 3 4 5 Time (years) 6 7 8 9 10
The progression of CKD can be delayed if recognition is early and treatment adherence is achieved. The natural history of the CKD phases can be from months years decades, influenced by the before mentioned factor together with the cause of the CKD and the general well-being (health) of the individual. Often the signs and symptoms Of CKD are late in presentation and the patients are diagnosed at CKD 45 phase offering little opportunity to delay the progression to CKD5 and the need for renal replacement therapies. However the importance of early recognition not only delays the progression and also
increases the likelihood of ultimately better outcomes for the CKD 5 patient. A great deal of emphasis has been placed on pre-ESRD (CKD5) management to achieve this target. Primary Prevention: SCREENING Secondary Prevention: Delay the progression Tertiary Prevention: Reducing the complications Fresenius Medical Care Asia Pacific
CDPB112013
16
INFLAMMATION The Oxidative Stress Story Oxygen, particularly certain chemical forms of oxygen, is highly toxic to biological entities. As evolution proceeded alongside increasing atmospheric O2 the primitive organisms alive then must have evolved ways to neutralize oxygen and species of bacteria with a highly developed O2 resistance somehow closely related themselves to other evolving organisms. And they persist today in our cells: not as viable bacteria but as a cell organelle called the mitochondrion: our cells have 100s to 1000s of mitochondria more if the cell is more metabolically active. These mitochondria even have their own DNA a residue of the original bacterial DNA and it does work as DNA, controlling various metabolic pathways mainly involved in converting toxic O2 into useful energy. Interestingly, we inherit our entire mitochondrial DNA. O2 is highly toxic and yet is essential to metabolism and energy generation. To deal with this dilemma the body has developed systems for transporting and storing oxygen in a way that the oxygen toxicity is neutralized. We breathe atmospheric oxygen via or lungs where it is immediately transferred to and bound to hemoglobin in red blood cells neutralized. Only tiny amounts of free, dissolved oxygen are found in blood. At the cell, the O2 is transferred from Hb to other molecules which usually contain one or more heme proteins and these proteins either transfer the O2 to the mitochondria (those clever bacteria of old) or may temporarily bind the oxygen in storage form. The mitochondria immediately get to work turning the O2 in water and carbon dioxide by oxidizing sugars and lipids and generating energy and heat along the way (see later). The mitochondrial oxygen sump is fairly effective but about a percent or so of the oxygen processed does actually leak out as what are called radical oxygen species (ROS). The leak rate increases when cells are very active metabolizing food substrates (like when we overeat). There is another situation where there is a potential for a large release of ROS when white blood cells called phagocytes attack invading bacteria or other foreign material. The white cells actually generate large amounts of ROS and other free radicals to kill the bacteria bit like our using bleach or other oxidants to kill germs. In this case lots of ROS leak into the surrounding tissue and the circulation and could do a lot of collateral damage. Not surprisingly, there is a balance various antioxidant chemicals and enzyme systems in cells, blood and tissues. Normally antioxidants are sufficient to counteract a systemic effect of ROS. Deficient antioxidant systems or excess ROS or their combination leads to a state known as oxidative or oxidant stress. Free radicals and ROS cause disease by altering the structure and function of essential biomolecules. Such changes may be reversible or irreversible. Oxidative alteration may be reversed but in many cases oxidation proceeds to a stage where it is not reversible and produces permanent long-lived (sometimes called advanced) oxidation products. In some cases, e.g., AOPPs and AGEs, the oxidation products retain their own pro-oxidant potential and therefore promote further oxidative stress. In recent years many oxidative markers have been measured in patients with CKD and dialysis patients.
CDPB112013
17
Uremia is associated with evidence of increased oxidation of all biomolecules and in some cases the markers of oxidation reach extremely high levels compared to healthy controls. Additionally, there is evidence of reduced (or consumed) levels of both plasma and cellular antioxidant system. Uremia is a state of oxidative stress and as the stages of CKD advance, the intensity of oxidative stress also increases. However, certain markers of oxidative stress are present even before there is much loss of residual renal function suggesting that oxidative stress is not purely a failure to excrete oxidants but that the kidneys may have some general, protective antioxidant function.
A uremic toxin that has received considerable attention in recent years is homocysteine (Hcy). Hcy is not per se an oxidant but seems to be intimately related to oxidative processes e.g., in endothelial and vascular cells, which may explain its association with increased risk of atherosclerosis. Liver cells respond to pro-inflammatory cytokines (particularly IL-6) by altering their production of proteins. Activated by IL-6 hepatocytes increase the synthesis and release into the blood of c-reactive protein (CRP), serum amyloid A protein (SAA), fibrinogen (a clotting factor) and many others. These proteins are known as acute phase proteins (APP) or acute phase reactants. At the same time, the liver cells reduce their synthesis and release of other proteins, most notably albumin but also pre-albumin and transferrin. Liver production of cholesterol is also reduced. Thus the APR is characterized by elevated concentrations in plasma of CRP, fibrogen etc. and reduced concentration in plasma of albumin and cholesterol. Uremia is a state of chronic, low-grade activation of the inflammatory system. Typical findings confirm elevated plasma levels of inflammatory cytokines (e.g., IL-6) and acute phase proteins (e.g., CRP) and suppressed action of inflammation-modulating or anti-inflammatory mediators. Chronic inflammation in CKD is not the result of a single factor activating the cellular and humoral inflammatory pathways. CKD AND THE INFLAMMATORY CONSEQUENCES
Factor D Free radicals Carbonyls Glycoxidation AGE products
Inflammation
ADMA
Nitric oxide Cytokines Growth Factors

L-arginine
APR Endothelial
Fetuin
Injury Homocysteine
Lipoxidation
Calcification Thrombosis
Dyslipidemia
Atherosclerosis
Metabolic disorders
It is certain that some (and possibly many) uremic toxins can activate inflammatory pathways or suppress inflammation modulating factors but it also possible that the kidneys have a more generalized antiinflammatory function which somehow depends on intact kidney tissue mass. Fresenius Medical Care Asia Pacific
CDPB112013
18
As excretory function declines and kidney mass is lost, a pro inflammatory state results. The importance of chronic inflammation in CKD is that the markers of this state (e.g., high IL-6 or CRP) are strong predictors of morbidity and mortality and in particular mortality related to atherosclerosis and cardiovascular disease. The Message: The loss of renal function results in a total state of dysfunction from the cellular metabolic level that leads to a continuous decline is effective cellular function resulting in increased demand and dysfunctional responses, increased energy demands and altered transport mechanisms. The message to take away from this discussion about CKD, uremia (and dialysis) is to stop thinking of CKD as a disease where you can simplify to cause-effect-treat. Its a complex of disease states with physiological adaptations and pathophysiological maladaptations where eventually the sum of maladaptation imposes a risk of death.
Uremia in the sense of retained uremic toxins is only a part of the complex and, as we are now learning, we have to change the focus (e.g., to inflammation, oxidative stress, dysmetabolism, cardiovascular risk management) if we are to make additional progress towards better patient outcomes. Therefore the process is not a simple loss of renal function = uremic symptoms, but a complex disruption in homeostasis that occurs at the cellular level.
CKD TREATMENT OPTIONS When renal function is progressively loss there are adaptive mechanisms that partially compensate as more function is lost the load becomes > and symptoms (that we have now recognized are related to CKD) becomes present (refer back to KDOQI staging of CKD (1.5.1.2). Finally when enough renal function has been lost and CKD5 criteria have been reached then the treatment options include: 1. Palliative care 2. Dialysis (usually Hemodialysis, but in some countries more patients are encouraged to commence with Peritoneal dialysis self-care modality) 3. Preemptive transplant
CDPB112013
19
See the diagram below which highlights the options and the patient flow regarding treatment options.
Modality of renal replacement therapy
ESRD
No Treatment
Dialysis
Pre-emptive Transplant
Hemodialysis
Peritoneal Dialysis
Secondary Transplant
FLUID AND ELECTROLYTES In nephrology practice fluid and electrolyte assessment and management is critical. As the kidneys are essential for fluid and electrolyte homeostasis in the body, it is not surprising that when caring for clients with ESRD nurses need to be well versed in their understanding of fluid and electrolyte balance. In adults, approximately 60% of the body weight is comprised of fluid. The distribution of fluid and electrolytes within the body is considered as either intracellular or extracellular. Extracellular is further divided into Intravascular (Plasma) and Interstitial. The intracellular fluid, generally contributes to 40% of body weight and the intravascular 5% and the interstitial 15%. The fluid contribution to body weight varies with age, with the newborns fluid contributing to 70-80% of weight; puberty to 39 years of age 60% (males) and 52% (women); 40 60 years 55% (males) and 47% (women) and > 60 years males weight is 52% and womens weight 46% fluid. The noted difference in gender is related to fat contribution to weight increasing with age. This is one of the main reasons that both the young and older persons are vulnerable to fluid imbalances.
CDPB112013
20
Q. Think about your clients in the Dialysis Centre. How would you interpret the fluid status of an obese client? Why?
Volume (L) It is important to understand the volume and distribution of fluid when caring for persons with renal dysfunction, and specifically those undergoing dialysis. When we are dialyzing individuals with ESRD the fluid is removed initially from the intravascular (Plasma) compartment, with excess fluid then refilling the vascular compartment from the interstitial compartment through hydrostatic pressure forces. This is achieved through a capillary network that allows the filtration to occur. We term this physiologic process capillary refilling. Also we need to think of these compartments when we are undertaking our physical assessments. When we are assessing and evaluating the clients Ideal Dry Weight we evaluate the presence and degree of peripheral edema, as determined by pitting edema. This indicates fluid excess that has spilled over into the interstitial space from the vascular compartment and presents as trapped fluid in the tissues. Note that the fluid excess in the vascular compartment presents as hypertension. Q. In the Dialysis centre review your clients blood pressure and relate to their fluid status. Does it always correlate? Why not? ELECTROLYTES Electrolytes are ions in solution and in humans there is general electrical neutrality between compartments. The charges of the ions are either positive (captions) or negative (anions). The major electrolytes in humans are sodium, potassium, calcium, chloride, phosphate and bicarbonate. Captions include; Sodium, Potassium and Calcium. Anions include Chloride, Bicarbonate and Phosphate. The Major extracellular cation is sodium, while the major intracellular cation is potassium.
CDPB112013
21
PLASMA ELECTROLYTES Captions Sodium 135-144 Mm/L Potassium 3 5 Mm/L Calcium 2.2 2.6 Mm/L Magnesium 0.6 1.0 Mm/L Total = 152 Anions Chloride 100 Mm/L Bicarbonate 22 30 Mm/L Phosphate 0.6 1.3 Mm/L Organic salts, Sulfate and other anions Total = < 152 (anion gap of 8-16)
INTRACELLULAR FLUID ELECTROLYTES Captions Potassium 150 -160 Mm/L Magnesium 16 20 Mm/L Sodium 10 Mm/L Total Captions = 190 Anions Phosphates & sulfates 150 Mm/L Bicarbonate 10 Mm/L Other Anions 20 - 30 Total Anions = 180-190 The body expends energy to maintain this balance of captions and anions together with the greater concentration of sodium in the extracellular fluid. The body achieves this by cellular Sodium-potassium pumps that require energy derived from ATP ADP conversion.
CDPB112013
22
FUNCTIONS OF BODY FLUIDS Fluid and electrolytes move in between the body compartments by many processes, some passive some active, but they primarily include the following: 1. Osmosis: - The movement of fluid from low solute concentration to high solute concentration. Certain solutes/electrolytes have high osmotic properties that attract fluid and encourage fluid movement. These solutes include sodium, glucose and proteins. An example is when a Diabetic client has high blood sugar level then the client complains of thirst, increasing the intravascular volume that then drives the Glomerular filtration rate that facilitates some clearance of glucose.
Low solute concentration Semi permeable membrane
Movement of Fluid
2. Diffusion: - The movement of solute from a high solute concentration to a low solute concentration. Diffusion can be passive, depending on the concentration gradient across the Semipermeable membrane, or can be active utilizing energy derived from ATP-ADP conversion; Na+- K+ pumps are an example of active diffusion, that use energy to move solutes across the cell membrane to maintain cell integrity.
Solutes moves from side of higher concentration to side of lower concentration across semi-permeable membrane (Larger solutes move slower and there is membrane resistance)
CDPB112013
23
3. Filtration: - The movement of fluid together with dissolved solutes from a region of high pressure to that of lower pressure; the force behind it is hydrostatic pressure. The transfer of fluid and solutes across the arterial capillaries to the interstitial fluid is an example of filtration. In this example the pressure inducing the filtration is that of blood pressure created by the heart (pump pressure) and the vessel diameter.
UREMIC TOXINS The term uremia is also used to describe the illness the accumulation of symptoms (patient complaints) and signs (observed abnormalities) - that may occur in patients with chronic kidney disease (CKD) and for which a laboratory marker of this illness is excess urea in blood. It is appropriate to use the term uremia in both senses 1) simply to indicate high blood urea level and 2) to summarize a (complex) illness that is association with impaired function of the kidneys. The uremic toxins so far identified can be classified in various ways. Some are derived mainly from the diet and are exogenous: phosphates derived mainly from dietary protein are an example. Others are endogenous produced when substrates are metabolized: urea is a product of protein metabolism; creatinine is the product of metabolism of muscle creatine phosphate. Others still are the result of chemical alteration of normal chemicals: e.g., molecules changed by exposure to reactive oxygen in oxidative stress. The classification of uremic solutes by size is into small, middle and large: the actual classifications vary somewhat but the ranges indicated above provide a sample. Very importantly, the uremic toxins can be classified as those that dissolve readily in water water soluble and those that do not (these are fat soluble). Normal renal function (and dialysis) affects removal of water soluble solutes. However, water soluble solutes of any sizes may bind to protein in plasma or on the cell surface protein bound. If these were in free form they might be dialyzed but the bound forms are not dialyzed since the dialyzer membranes are not permeable to proteins. Uremia toxins of any type or size are likely to also bind to and in tissues tissue bound form. Obviously the tissue bound form is not immediately accessible for removal by dialysis.
CDPB112013
24
Classification of Uremic Toxins
Not Dialyzable
Urea has remained the most commonly used chemical marker of impaired renal function and uremia. Also, the kinetics of urea is relatively readily definable without complicated models e.g., the volume of urea distribution approximates body water and urea diffuses readily throughout this volume. Since urea is the most abundant end-product of protein metabolism, and the generation side of the urea kinetic equation provides potentially useful information regarding protein nutrition, further advocates Urea as a marker. However, as is increasingly recognized, the correlation between blood urea concentration and the severity and scope of uremic toxicity is incomplete. Effectively, uremic toxicity cannot be summarized by the concentration of a single, small solute and urea measurement and definition of urea kinetics is limited for full quantification of dialysis efficiency. Unfortunately, there is no consensus for an alternative marker so urea and its kinetic analysis remain our best attempt at dialysis quantification. There is an interesting Website EuTox.com that identifies new Uremic Toxins that you might find interesting to visit. The important consideration is that we still dont know all the uremic toxins we do know that Normal renal function clears at the Glomerular level substances up to almost 70,000 Daltons MW inferring that if we are to replace renal function by dialysis we need to mimic this to some degree.
CDPB112013
25
PRINCIPLES OF DIALYSIS Hemodialysis uses principally the processes of diffusion, ultrafiltration and convection. Diffusion (movement of solute from an area of high to low solute concentration) requires a concentration gradient of the solutes this is achieved by the: 1. Qb and the Qd rates, 2. Dialyzer membrane (semi permeable pore size that allows the particular solute to pass through the membrane) 3. Surface Area of the dialyzer 4. Thickness of the dialyzer membrane 5. Temperature for kinetic movement 6. Time along the membrane for concentration difference recognition and for action 7. Counter-current flow of dialysate and blood; flow geometry optimizing the opportunity for diffusive process
CDPB112013
26
Ultrafiltration is the movement of fluid across a semi-permeable membrane from an area of high to low pressure. This process is achieved partly by the Hemodialysis machine applying negative (vacuum) pressure on the dialysate side of the circuit and secondly the hydraulic nature of the dialyzing membrane (KUF).
Convection is the movement of solutes with the fluid floe (solvent drag) the movement of membrane permeable solutes with ultrafiltrated fluid. This process of solute transport is effective for solutes up to and including 40,000Da MW.
(Hemo Dia Filtration) - a combination of diffusive and convective processes has been the focus for more effective (efficient) dialysis as it mimics more closely the renal transport and fluid processes. It is now recognized that Diffusive process are important for small molecular weight substances (e.g. Urea, Creatine), while Filtration (convective process) are important for the Middle to larger MW solutes (e.g. B2Microglobulin, iPTH, and a number of the inflammatory mediators Uremic toxins). Therefore a combination of the 2 processes is a logical conclusion. HEMODIALYSIS Chronic hemodialysis has been in practice for more than 40 years and although we have increased understanding and practice of hemodialysis there remains some challenges to dialysis clinicians. Conventional hemodialysis does not mimic well the homeostatic functions of the kidneys, with short intermittent dialysis resulting in swings of solutes and fluid and resultant patient symptoms contributing to the increased morbidity (short term) and mortality (long term).
CDPB112013
27
Thereby some of the challenges in practice include more effective management of clients fluid status, protection and management of cardiovascular risks, nutrition, biocompatibility, improved vascular access survival and more effective measures of dialysis adequacy. One strategy that has evolved over the past decade is that of enhanced dialysis or daily dialysis, with some promising early results, however this approach also needs increased research and analyzed by clinical effectiveness and health economic measures. THE HEMODIALYSIS MACHINE
The Hemodialysis has evolved over the history of dialysis; increasing its safety and reliability significantly. Clinical staff needs to understand the functioning of the machine in order to mange it safely and also the patient. THE EXTRACORPOREAL CIRCUIT
CDPB112013
28
Qb and Negative Pressure

Effective Qb in % of nominal Qb
100
80
Effective blood flow = F * nominal blood flow
60
40
20
0 -700
-600
-500
-400
-300
-200
-100
Pre-pump pressure [mm Hg]

The role of Albumin
ARE YOU DELIVERING THE PRESCRIBED Qb?
Monitoring pressures
Arterial drip chamber Pressure transducer protector
Anticoagulant pump
Dialyzer
P Pvenmonitor
higher positive pressure

Arterial blood pump Venous drip chamber
Air detector Thrombus filter
Part monitor
negative pressure
Pressure transducer protector Arterial needle
Venous line clamp
lower positive pressure
Venous needle
The role of Albumin
CDPB112013
29
ULTRASONIC AIR DETECTORS
THE FLUID FLOWS & HYDRAULICS
CDPB112013
30
CDPB112013
31
THE BALANCING CHAMBER CRITICAL ADDITION IN THE CONTEMPORARY HEMODIALYSIS MACHINE
CYCLE 1
CYCLE 2
CDPB112013
32
SAFETY & USER FRIENDLINESS BLOOD CIRCUIT ALARM Audio Visual Blood pump stops Line clamp activated DIALYSATE CIRCUIT ALARM Audio Visual Bypass
USER FRIENDLINESS
CDPB112013
33
Summary
The next section of the course analyses methods and strategies for achieving fluid balance as well as determining the clients Ideal Dry Weight and the justification for focusing on fluid homeostasis in the ESRD population. THE RELATIONSHIP OF FLUID, HYPERTENSION AND CVD
REQUIREMENTS FOR HEMODIALYSIS The requirements for hemodialysis include: 1. Dedicated staff that are trained to understand the technologies and the needs of the patients 2. Hemodialysis machines; ensure the extracorporeal and dialysate circuits deliver and ensure safety of the patient at all time 3. Dialyzer membrane that is predictable and reliable ; biocompatible as much as possible 4. Vascular access; Chronic access (AVF, AVG) 5. Water Treatment System 6. Dialysate management; In-house, on-line or liquid (manufactured) 7. Standard Operating Procedures (SOPs, Clinical Policies & procedures) 8. Infection Control Standard Precautions (Dialysis) 9. Patient Management (Clinical Management Systems) Long term management 10. Documentation and Surveillance System to ensure quality; CQI, Clinical Management System Fresenius Medical Care Asia Pacific
CDPB112013
34
11. Rehabilitation program; long term outcomes & 12. Patients
DIALYZER MEMBRANES Dialyzer membranes, because of their close proximity to patients blood need to be as biocompatible as possible; current, contemporary dialyzer membranes are synthetic; Polysulfone, polyacrylonnitrile and Polyamide. The functions we require to achieve with a dialyzer are essentially two solute exchange between blood and dialysate and fluid removal from the patient. At its most basic a dialyzer is an exchanger designed to permit the exchange of water and solutes between blood and a physiological electrolyte solution dialysate. The functions that need to be contained in dialyzers
CDPB112013
35
These exchange functions occur across the dialyzer membrane which is designed and fabricated for selective permeability. It follows that the minimum requirements for a dialyzer include a membrane which separates a blood flow path or channel from a dialysate flow channel. Both blood and dialysate flow channels need entry and exit ports. All of these components are contained in a casing or casket (also called housing). The arrangement of the components within the casing is such that the flow paths for blood and dialysate are separated by a sealing process known as potting. In the diagram below, the arrangement of the membrane as hollow-fibers is shown, providing a flow path for blood within the lumens of the fibers and a flow path round the fibers for dialysate is shown here in longitudinal and cross section.
Hollow Fibre dialyzers
cross section long section
dialysate path blood path membrane
The role of Albumin
Diagram showing the blood and dialysate flow paths
CDPB112013
36
COMPONENTS OF THE CONTEMPORARY DIALYZER (FX-Dialyzer) Dialyzer membranes are categorized by the term flux low flux, high flux. The term flux as applied to dialyzer membranes correctly refers to their permeability to water defined by the measurable ultrafiltration coefficient (KUF) of the dialyzer. In units KUF is mL of water (filtrate) flow per 1 mmHg difference in hydrostatic pressure across the membrane (transmembrane pressure: TMP) per hour mL.mmHg1.hour1. The KUF of the dialyzer membrane is determined by the proportion of the membrane that has open pores the product of pore density and average pore size. Although not fully standardized, the terms low, middle, high and super flux approximate the KUF values shown in picture below. If KUF is normalized to surface area of membrane in the dialyzer and assuming a fairly standard pore density per unit area, KUF is proportional to pore size. It follows that larger solutes will diffuse across higher KUF membranes more readily than membranes with lower KUF. When referring to solute clearing capacity of membranes and dialyzers we should refer to a grading of their solute permeability low, medium, high.
During dialysis there are three relevant pressures the hydrostatic pressure of dialysate, the hydrostatic pressure of blood and the oncotic pressure of blood. The dialyzer during dialysis is dynamic regarding all these pressures. 1. The dialysate is pumped or drawn from the dialyzer (the dialysate pump operates downstream of the dialyzer). Relative to zero pressure, the pressure at the dialysis outlet is more negative than the pressure at the dialysis inlet because pressure is dissipated (lost) due to resistance to dialysate flow through the dialyzer. 2. Blood is pumped through the dialyzer (the blood pump operates upstream of the dialyzer). The pressure in blood (in the fibres) is maximum at the blood inlet and dissipates due to resistance to flow along the length of the fiber.
CDPB112013
37
3. Oncotic pressure due to the action of plasma proteins is lowest at the blood inlet but because of removal of fluid and concentration of proteins rises towards the blood outlet. If all these pressure changes were changing linearly along the length of the dialyzer the average or net transmembrane pressure (TMP) would be as represented by the formula in diagram below. Linear change is a good approximation for dialysate pressure but the changes in the blood and oncotic pressures are not linear and not exactly predictable.
Dialyzer hydraulic permeability
DialysateOUT
Relative to zero TMP PDout < PDin PBin > PBout Bout > Bin PDout Bin PBin PDin Bout PBout
DialysateIN
BloodIN
TMP [(PBin + PBout )/2]-[(PDout + PDin)/2]-[(Bout + Bin )/2]
BloodOUT
The role of Albumin
Modern dialyzers may have KUF in excess of 40 mL mmHg-1.hour-1. A difference of 20 mmHg in TMP would mean a difference in UF of 800 mL per hour or > 3L in a session of 4 hours. That would create serious problems for the patient. For this reason modern dialysis systems do not create a TMP to determine ultrafiltration. They remove a precise volume of dialysate from a dialysate hydraulics that is effectively a closed system where dialysate inflow and outflow are exactly balanced and equal (will be explained in detail in later modules). In such a system removing some of the dialysate forces an equal volume to be replaced in the dialysate circuit by a flow of fluid across the membrane from the patients blood. At a point along the dialyzer length the pressures reverse and there is zero TMP and no filtrate flow. Beyond that point the dialysate pressure now exceeds the pressure in the fiber and water flows from the Dialysate into the fiber and effectively into the patients blood. This is the phenomenon of back filtration. The point along the length of a dialyzer where the pressures reverse is the isobaric (equal pressures) distance or length and will vary depending upon the set UF (at the UF pump) and the membranes water permeability. Moreover, the isobaric point changes during dialysis due to changes in the patients blood density, protein content and oncotic pressure resulting from removal of plasma water from the blood. At any set value for UF the isobaric point is further from the blood inlet end as water permeability of the membrane (~ dialyzer KUF) falls and nearer to the blood inlet as KUF rises. Thus, at any set UF backfiltration is larger for high flux compared to low flux dialyzers. For any set membrane water permeability (KUF) the isobaric point is further from the blood inlet as UF rises and nearer to the blood inlet for lower UF. Thus, back-filtration is always higher when the UF goal is lower. Fresenius Medical Care Asia Pacific
CDPB112013
38
Backfiltration
DP HF-net
Forward filtration
Pressure mmHg
Back filtration Isobaric point

Lower set UF Higher KUF Higher set UF Lower KUF
The role of Albumin
The term internal filtration is used to describe this phenomenon which occurs almost invariably with modern dialyzers. The filtrate formed at the blood inlet end is drained to the dialysate outlet. The dialysate that enters the blood flow in the capillary comes mainly from the fresh dialysate at the dialysate inlet and joins the blood leaving the dialyzer; what is happening is a version of post dilutionhemodiafiltration. Some of the volume of filtration formed at the blood inlet end of the dialyzer is replaced by dialysate at the blood outlet end.
Internal filtration
DialysateOUT DialysateIN
BloodIN
Isobaric point
BloodOUT
The role of Albumin
CDPB112013
39
SUMMARY POINTS & DIALYZERS (MEMBRANES)
CDPB112013
40
DIALYSIS DOSE & ADEQUACY OF DIALYSIS How much dialysis is enough? We have just discussed the benefits, especially related to the cardiovascular system, of daily more frequent dialysis. The Clinical Practice Guidelines (CPGs) advocate an achieved spKt/V of at least 1.3 (1.4) (See http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_uptoc.html#hd hemodialysis Adequacy Guidelines). Gotch and colleagues were the originators of the formula for determining Adequacy of dialysis through Kt/V calculation (See Gotch and Port commentary on the HEMO study). The Kt/V equation formulation has a basis in Pharmacokinetics, with clearance (K) and volume distribution (V) integral to the calculation. There remain a number of controversies related to Dose/Adequacy of dialysis including: Relationship of V to clinical outcomes: as the denominator of the equation as V increases the calculated Kt/V diminishes. Thereby as the client increases weight their Kt/V decreases, however clinically they may be doing well, eating and gaining body weight. However a client who is eating more is also generating greater amounts of nitrogenous wastes, and unless these are removed, over time they will eventually impact on the clients overall well being. Often the disparity between the Kt/V result and clinical presentation and client history: there could be a lag time related with the estimation of clearance and the clients signs and symptoms. The blood sampling method to determine the calculated Kt/V is also fraught with errors. Kt/V is based on small molecular weight (MW) solute clearance (Urea kinetics) and the question remains as to whether this is the marker to determine dosing and adequacy of dialysis or whether middle MW solute clearance should also be measured: Thereby there remain some issues in practice regarding the Dialysis Dose and Adequacy of dialysis. Much of the current focus in the improvement of dialysis is related to determining the significant components of Uremia that require correction or modification to improve the clinical effectiveness and optimal client outcomes. Websites related to Dose of Dialysis/Adequacy of Dialysis: http://www.kidney.org/professionals/kdoqi/guidelines_updates/doqi_uptoc.html#hd KDOQI Adequacy Guidelines http://www.cari.org.au/dialysis_adequacy_publ2000.php CARI Adequacy CPG (Australian) http://www.hdcn.com/calc.htm Calculation tools (HDCN website) http://www.ndt-educational.org/guidelines.asp European Best Practice Guidelines Overview Readings: De Palma JR. and Pittard JD. (2001) Dialysis dose (Part 1). Dialysis and Transplantation. April. PP. 251 260. De Palma JR. and Pittard JD. (2001) Dialysis dose (Part 2). Dialysis and Transplantation. May. PP. 315 .323. Fresenius Medical Care Asia Pacific
CDPB112013
41
Leading Authors: Charra B. (2001) Is Kt/V urea a satisfactory measure for dosing the newer dialysis regimens? Seminars in Dialysis. Vol. 14,1, pp. 8-9. Lindsay RM and Sternby J. (2001) Future directions in dialysis quantification. Seminars in Dialysis. Vol. 14, 4, pp. 300-307. Syme, SW, Hootkins RE and Will EJ. (1998), solute clearance and tissue clearance times. Seminars in Dialysis. Vol. 11, 3, pp. 185 188. Other readings: - Goodkin, DA, Mapes, DL and Held, PJ. (2001). The dialysis outcomes and practice patterns study (DOPPS): How can we improve the care of hemodialysis patients? Seminars in Dialysis. Vol. 14, 3, pp. 157 159. EQUATIONS: Also see the Adequacy PowerPoint for more details together with the readings and Text. Besides URR, these formulae are easy to compute in your PDA, Scientific calculator or computer. 1. URR (Urea Reduction Ratio) URR = {Pre dialysis Urea Post dialysis urea} X 100 Pre dialysis Urea The URR remains the most frequently used measure of Dialysis Dose due to ease of calculation and understanding. The CPGs advocate a minimum URR of > 65% (70% by the CARI guidelines) 2. LINEAR FORMULA R = post Urea/Pre Urea UF = pre dialysis weight post dialysis weight W = post dialysis weight This formula considers that there is a linear relationship between the R and Kt/V. This assumption is not correct, however the Kt/V can be easily calculated and provides a rough estimate. 3. LOGARITHMIC FORMULA This is Daugirdas equation that is utilized in most Dialysis programs. Kt/V = (-In [R 0.008t]) + ([4-3.5 R] X [UF/W]) In = natural logarithm (e on Scientific calculator) Kt/V = 2.2 (3.3 X [R {0.03 UF/W}])
t = duration of dialysis in hours R = post Urea/Pre Urea UF = pre dialysis weight post dialysis weight W = post dialysis weight 4. CORRECTION FOR 2-POOL (Double Pool) Adjusting for the Rebound Fresenius Medical Care Asia Pacific
CDPB112013
42
The two formulae for estimating the equilibrated Kt/V (eqKt/V) from the unequilibrated single pool Kt/V (spKt/V) are adjusting the spKt/V result for the rebound that occurs some 30 - 40 minutes post dialysis as the urea and other solutes equilibrate between the Extracellular (Vascular and Interstitial) and Intracellular compartments (hence the terminology equilibrated). The correction factor is further adjusted for the type of vascular access; venous (Central Venous Dialysis Catheter) and the conventional arteriovenous access (AVF and AVG): A-V vascular access: eqKt/v = Kt/V (0.6 x [{Kt/V}/t]) + 0.03 CVDC (venous): eqKt/V = Kt/V (0.4 X [{Kt/V}/t] + 0.02 Why is there need for the adjustment related to the type of vascular access? Discuss spKt/V and eqKt/V as effective measures for clearance/adequacy. Another consideration when prescribing dialysis dose, is not just the solute clearance but also effective fluid clearance. Fluid imbalance associated with ESRD, contributes to clients hypertension and over time LVH (Left Ventricular Hypertrophy) linking to their Cardiac morbidity and mortality risk. Considering the need for fluid homeostasis becomes a critical component of clinical management, both in the short and long term survival of ESRD population. We will be discussing this further in the Fluid Management and Assessment section.
Vascular Physiology & Long Term Survival of Vascular Accesses in RRT Hemodialysis therapy is reliant on the adequacy of a vascular access. Optimal clearance associated with dialysis relies on the Dialysate flow rate, membrane permeability and surface area, dialysis time and the blood flow rate through the dialyzer. The Qb is dependent on the vascular access flow rate for clearance and mimics the relationship between renal blood flow, filtration (at the Glomerulus) and opportunity for clearance; diminished Glomerular blood flow results in a reduction in GFR and clearance. Dysfunctional vascular access will thereby adversely affect dialysis adequacy and result in increased patient morbidity and mortality. Nurses are integral in managing the vascular accesses to assure both the adequacy of dialysis and survival of the access. Various vascular accesses are used for hemodialysis procedure, including: 1. Percutaneous vascular access; Jugular, Femoral or Subclavian vein catheters, which are used either temporarily or permanently. 2. Arteriovenous Fistula (AVF) or Grafts (AVG). The AVF is the preferred vascular access, with evidence of long-term survival, reduced complications and improved flow rates, compared to the other options.12 The challenges with vascular access care for the dialysis clinical team, relate to: Creation of the vascular access (Surgeon or Interventionist Nephrologist or Nurse Practitioner (evolving role); especially in patients with peripheral vascular disease, elderly patients and those with diabetes mellitus.
CDPB112013
43
Maintenance of the vascular access; increasing survival, reducing complications (thrombosis, stenosis, aneurysm) Reducing the pain associated with cannulation. Increasing the predictability and reliability of successful access to the vascular access blood flow. Effective utilization of vascular access for daily more frequent dialysis (contemporary approach to achieving more homeostatic management of fluid, electrolyte and uremic waste clearance).
VASCULAR ACCESS ASSESSMENT The patients arterial, venous and cardiopulmonary system determines the most viable access for the patient. The assessment includes: History; Previous sited vascular accesses; Central catheter history; Pacemaker; Congestive heart Failure; Peripheral Vascular Disease; Diabetes and associated vessel disease. Physical examination Doppler evaluation Scheduling of vascular access creation; Preservation of peripheral vessels by avoiding venipunctures. AVF construction at least six months prior to anticipated commencement of dialysis, based on the trend of rising plasma Creatinine. Ideal referral to vascular surgeon when serum Creatinine around 400mol/L (4mg/Dl). Activity 1; Develop a strategy for the preparation of patients for vascular access. It may be useful to incorporate an algorithm related to their morbidity and risk status and relate to selection of dialysis vascular access. Activity 2: Regarding vascular assesses summarize the benefits for the various vascular accesses used for hemodialysis. It would also be useful to group the patient population under the following categories: Elderly, Diabetes and Cardiovascular disease. Analyze AVF and AVG and the KDOQI Vascular access CPGs and develop a framework for selection and management of these vascular accesses. Percutaneous hemodialysis catheter utilization is quite prevalent in practice What are the practices that are used to reduce complications? Define the following terms: AV Fistula _______________________________________________________________ _______________________________________________________________ AV Graft _______________________________________________________________ _______________________________________________________________ Aneurysm _______________________________________________________________ _______________________________________________________________ Bruit _______________________________________________________________ _______________________________________________________________ Fresenius Medical Care Asia Pacific
CDPB112013
44
Infiltration _______________________________________________________________ _______________________________________________________________ Pseudo aneurysm _______________________________________________________________ _______________________________________________________________ Recirculation _______________________________________________________________ _______________________________________________________________ Stenosis _______________________________________________________________ _______________________________________________________________ Thrill _______________________________________________________________ _______________________________________________________________ Thrombosis _______________________________________________________________ _______________________________________________________________
CLINICAL OUTCOMES IN DIALYSIS - CLINICAL INDICATORS 1. Anemia Management a. Hb level 11-12 gm/dL b. TS% 22-50 2. Bone Management a. Phosphate pre dialysis < 5.5 (5.0) gm/dL b. Calcium 8.8 9.8 mg/dL c. iPTH d. Calcium X Phosphate 3. Fluid and BP control a. Interdialytic fluid gains < 3-5% of EDWt b. BP normalized 140/80 mmHg 160/80-90 mmHg) 4. Nutrition a. Albumin level b. nPNA c. HCO3 5. Adequacy of HD a. spKt/V 1.4 (3 sessions per week) b. More frequent dialysis sessions c. Convective therapies - OL-HDF d. Diabetic population needs
CDPB112013
45
ANAEMIA MANAGEMENT The challenges in Renal Anemia management focus on achieving the target 11-12 g/dL Hemoglobin in the most cost-effective manner. Understanding the factors contributing to the Anemia, as well as those that impact on erythropoiesis aids in the effective management. The predominant cause of anemia in CKD is reduced or insufficient production of Erythropoeitin (EPO) other factors include Iron deficiency and Vitamin B12 and folate deficiency. Correcting the anemia has been found to have a significant impact on cardiovascular well-being as well as Health related quality of life. Thereby Therapy should be targeted at the following: Replacement of EPO (individualized) Iron therapy (usually IV; KDOQI, CARI) Vitamin B and folate replacement. When assessing the effectiveness of treatment and/or poor response the following should also be assessed: Nutrition and overall well-being Active Inflammatory condition Adequacy of dialysis Renal Osteodystrophy; Osteitis Fibrosa associated with Secondary hyperparathyroidism
KDOQI GUIDELINES ANEMIA MANAGEMENT
http://jasn.asnjournals.org/content/14/10/2654/F1.expansion.html Fresenius Medical Care Asia Pacific

CDPB112013
46
RENAL OSTEODYSTOPHY Renal Osteodystrophy begins in the mild to moderate phase of CKD and continues to be the Achilles heel in management of ESRD. The contributing factors to the raised iPTH, leading to Osteitis Fibrosa includes: Reduced effective 1,25 DHCC Raised serum phosphate Reduced ionized calcium Raised iPTH Dialysis thrice weekly is not very effective at controlling the phosphate; however success has been reported with enhanced dialysis therapies, clearing the phosphate before it can settle in the intracellular compartment. Management of bone disease incorporates the following, titrated to the individual: Phosphate binders; Calcium, cationic polymer, Aluminum and compounds. Vitamin D therapy; results problems in management = hypocalcaemia (action of Vitamin D) and high calcium phosphate product with increased risk of metastatic calcification. Parathyroidectomy Auto implant of Parathyroid gland
CDPB112013
47
Serum phosphate (Pi, PO4) should be measured every 4-12 weeks to adjust therapy with phosphate binders. This can be done using the phosphate algorithm below:
http://renux.dmed.ed.ac.uk/edren/Handbookbits/HDBKosteodyst.html#PO4 Also Visit: http://www.kidney.org/professionals/kdoqi/guidelines_commentaries.cf CARDIOVASCULAR (Blood Pressure and Fluid Management) The cardiovascular risk for ESRD patients relates to more than just fluid imbalance and hypertension, although it is critical to address these aspects. There are some interesting early results with pharmaceutical agents STATINS, which besides lowering and controlling the dyslipidaemia appear to offer further cardiac protection. Other factors that should be considered in care planning include: Adequacy of dialysis Biocompatibility Exercise Nutrition Anemia correction Effective management of calcium, iPTH and phosphate
CDPB112013
48
FACTORS IMPLICATED IN THE PATHOGENESIS OF HYPERTENSION IN ESRD TARGET:
TARGET: REDUCE INFLAMMATION (Adequacy of dialysis, Clearance of Uremic toxins, Biocompatibility)
CDPB112013
49
HYPERTENSION MANAGEMENT SCHEMA 20
Regular nutritional assessment of ESRD patients is paramount to ensuring optimal well-being and evaluation of the adequacy of the RRT. The ESRD population is at risk of malnutrition can be related to appetite and reduced intake, increased protein catabolism and finally due to losses > intake. The peritoneal dialysis population is at a greater risk of the latter, due to changes in the permeability of the peritoneum exacerbated by episodes of peritonitis. NUTRITIONAL ASSESSMENT APPROACH The KDOQI Nutritional CPGs advocate undertaking a nutritional assessment (Subjective Global Assessment SGA), at least every six months, unless there are indicators to further initiate an assessment. The nutritional assessment of ESRD patients includes the following: History Symptoms of nausea, vomiting and anorexia, recent changes in body weight. Presence of chronic diseases, Diabetes, GIT disturbances, depression and CVD. Assessment of food intake Analysis of patients diet recall. Organize patient to document food intake for at least 2 days. Physical examination Assessment of muscle and fat stores; upper and lower body comparison. Biochemistry Serum Albumin, acute phase proteins (C reactive protein), Urea, nPNA, phosphate and potassium.
CDPB112013
50
Anthropometrics and Bioimpedence
1. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. 2. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575. 3. Ozkahya M, Toz H, Qzerkan F, et al. Impact of volume control on left ventricular hypertrophy in dialysis patients. J Nephrol. 2002; 15:655660. 4. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351:12961305. 5. Grooteman MP, Nube MJ, Daha MR, et al. Cytokine profiles during clinical high-flux dialysis: no evidence for cytokine generation by circulating monocytes. J Am Soc Nephrol. 1997; 8:1745 1754. 6. Sitter T, Bergner A, Schiffl H. Dialysate related cytokine induction and response to recombinant human erythropoietin in hemodialysis patients. Nephrol Dial Transplant. 2000; 15:12071211. 7. Schindler R, ChristKohlrausch F. et al. Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens. Clin Nephrol. 2003; 59:447454. 8. Merello Godino JI, Rentero R, Orlandini G, et al. Results from EuCliD (European Clinical Dialysis Database): impact of shifting treatment modality. Int J Artif Organs. 2002; 25:10491060. 9. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. 10. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575. 11. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. 12. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575. 13. Ozkahya M, Toz H, Qzerkan F, et al. Impact of volume control on left ventricular hypertrophy in dialysis patients. J Nephrol. 2002; 15:655660.
CDPB112013
51
KDOQI GUIDELINES FOR ESRD PATIENTS
CDPB112013
52
Food intake factors in uremia

Physical accessibility Affordability
Adequate access to nutrients
Hedonistic Social eating
Adequate (not excess) balanced diet
Taste Palatability
Appetite, hunger & satiety
FOOD INTAKE
<<< balances >>>
NUTRIENT NEEDS
TAGLINE: A HUNGRY PATIENT IS A WELL DIALYZED PATIENT!
CDPB112013
53
INTRODUCTION TO NEW DIALYSIS TECHNOLOGY Main challenges in Renal Care The number of new patients with chronic kidney disease (CKD) is increasing. in the US, > 400,000 people have ESRD; 75% of these people require maintenance dialysis in Asia, CKD is becoming increasingly common due to the increasing prevalence of risk factors, eg, hypertension, diabetes and obesity.1 The typical CKD patient is older and is likely to have co-morbidities. In a study of CKD, mortality risk and cardiovascular (CV) events, Go et al reported that the mean age of CKD patients was > 60 years, increasing the likelihood of co-morbidities and treatment challenges CKD patients present with a high prevalence of co-morbidities, eg, CVD, hypertension and diabetes. Interestingly, Go et al observed that CV events increase as renal function deteriorates: reduced estimated glomerular filtration rate (GFR) was associated with an increased risk of death, AND increased CV events and hospitalization independent of known risk factors for, or a history of, CVD, the CV-event risk rose sharply for patients with an estimated GFR of < 45 ml/min per 1.73m2.1 Common HD therapies aggravate CVD risk: patient condition contributes to CVD; common HD therapies also aggravate CVD risk26 peripheral blood interacts unfavorably with dialyzer membranes in HD patients, affecting white blood cell (neutrophil) composition, which is related to the activation of immune system pathways. The resulting mix of HD-induced acute and chronic side effects is known as bioincompatibility direct cell membrane interaction and endotoxin-containing dialysis fluids directly enhance inflammatory cytokine release (active mediators of stimulated immune pathways), which are risk markers for CVD.3 Consequently, renal patients are exposed to a pro-inflammatory state:6,7 , the release of proinflammatory cytokines is believed to drive the pathophysiology of acute and chronic HD-related side effects, and puts patients at real risk of CVD events. 1. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351:12961305. 2. Grooteman MP, Nube MJ, Daha MR, et al. Cytokine profiles during clinical high-flux dialysis: no evidence for cytokine generation by circulating monocytes. J Am Soc Nephrol. 1997; 8:1745 1754. 3. Sitter T, Bergner A, Schiffl H. Dialysate related cytokine induction and response to recombinant human erythropoietin in hemodialysis patients. Nephrol Dial Transplant. 2000; 15:12071211. 4. Schindler R, ChristKohlrausch F. et al. Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens. Clin Nephrol. 2003; 59:447454. 5. Merello Godino JI, Rentero R, Orlandini G, et al. Results from EuCliD (European Clinical Dialysis Database): impact of shifting treatment modality. Int J Artif Organs. 2002; 25:10491060. Fresenius Medical Care Asia Pacific
CDPB112013
54
6. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. 7. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575.
Route map of CVD risk in dialysis patients
Route map of CVD risk in dialysis patients This illustration shows how CVD risk factors are exacerbated during dialysis, impacting on both vascular and cardiac health. During HD treatment, patients are likely to be exposed to risk factors for development of CVD:
Uremia-related risk factors (URF): inflammation, oxidative stress, salt/water overload, anemia and calcium-phosphate product Dialysis therapy-related risk factors (DRRF): membrane bio-incompatibility, endotoxins (water quality) and achievement of dry weight Traditional risk factors for CVD (TRF): hypertension, diabetes, dyslipidaemia and smoking. These risk factors contribute to pathways either via volume overload to cardiac remodeling and left ventricular hypertrophy (cardiac health), or via a pro-inflammatory state which causes endothelial injury and eventually atherosclerosis (vascular health).1-3 We will cover these pathways in more detail later in this presentation. 1. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. 2. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575. 3. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. Fresenius Medical Care Asia Pacific
CDPB112013
55
4. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575. 5. Ozkahya M, Toz H, Qzerkan F, et al. Impact of volume control on left ventricular hypertrophy in dialysis patients. J Nephrol. 2002; 15:655660. The Challenges Faced by Nephrologists 1. Healthcare providers face many challenges in the ever-evolving management of kidney disease. End-stage renal disease (ESRD) is a growing problem worldwide, and a high percentage of ESRD patients require maintenance dialysis. 2. Patients on maintenance HD are at increased risk of morbidity and mortality arising from direct, therapy-related problems. Nephrologists need to manage: 3. Common side effects of HD, eg, hemodynamic instability 4. Long-term complications of HD that may adversely influence prognosis, eg, CVD. 5. Efficient Hemodiafiltration has been proven to significantly reduce the mortality and morbidity burden in ESRD patients, and we are now equipped to meet these major challenges.
The Key to Improved Patient Outcomes
Cardiac Disease
Vascular Disease
CDPB112013
56
The Key to Improved Patient Outcomes
NOTES Fresenius Medical Care Asia Pacific

CDPB112013
57
5008 Advanced Therapy System Issues in Clinical Practice Fluid Management, (hypotension, hypertension, estimation of dry weight) Patients having cardiovascular disease or high risk of developing cardiovascular disease Exposure to contaminants and materials that will trigger inflammatory response Clearance of uremic toxins frequency of monitoring and what sort of toxins are cleared out Monitoring patient and ensuring safety during treatment with the increasing gap of nurse : patient ratio Activity: Label the component parts of the machine and discuss the OL-HDF Treatment according to the pre and post dilution mode.
Pre-dilution: ____________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________ Post dilution: ___________________________________________________________________ ______________________________________________________________________________ ______________________________________________________________________________
CDPB112013
58
Benefits are realized through the sum of its core components Providing hemodialysis currently involves using a large number of labor-intensive manual operations centered around the hemodialysis machine. The 5008 advanced therapy system revolutionizes the provision of hemodialysis by minimizing and facilitating routine procedures through the integration of its core components; the sum of their functions delivers the unique benefits of this system. Core components of the 5008 advanced therapy system Online Clearance Monitor An effective quality assurance tool to monitor the delivery of dialysis dose. Blood Pressure Monitor Automatically monitors blood pressure during dialysis. Blood Volume Monitor Automatically monitors and controls blood volume response to ultrafiltration and assists dry weight determination. bibag Generates ready-to-use natural physiological buffer solutions. FX-class Unique Helixone dialyzer membrane effectively eliminates a wide range of uremic toxins with minimal albumin loss. ONLINE HDF Currently acknowledged as the most effective dialysis treatment modality that comes closest to the elimination profile of the natural kidney. Blood Temperature Monitor Stabilizes cardiovascular response to hemodialysis and ultrafiltration, and monitors vascular access. DIASAFE plus A Fresenius Polysulfone filter for ultrapure dialysate fluid preparation, two DIASAFE plus filters for ONLINE therapy. Highest safety standards There are a growing number of patients requiring dialysis and daily routine in dialysis centers is becoming increasingly hectic, which increases the probability of errors during treatment. The 5008 advanced therapy system utilizes an innovative, sophisticated safety concept together with several treatment monitoring devices. Therefore, the 5008 assures care givers by delivering maximum patient safety whilst facilitating patient surveillance. Fresenius Medical Care Asia Pacific
CDPB112013
59
The 5008 advanced therapy system is designed to alleviate the daily routine dialysis by offering many features that minimize operational errors during treatment preparation. These features include: multiple automated tests and routines a clearly-structured, Extracorporeal Blood Module (EBM) a fully integrated patient surveillance system self-initiating functions e.g. Heparin, OCM, BTM, BVM and ONLINE HDF an automated disinfection program 2030 minutes battery life (depending on effective blood flow rate) in case of power failure Emergency button for quick response in case of emergency.
ONLINE HDF is integrated as standard into the 5008 advanced therapy system ONLINE HDF is the most effective dialysis modality and provides many benefits to renal patients, including: CV stability1 Lower morbidity and higher survival in high-risk patients, eg, ESRD patients. Reduced mortality risk compared with other dialysis modes. The convective clearances that enhance large molecule removal have a substantial impact on survival in dialysis patients.2 The combined effect of these clinical benefits enhances patient comfort and quality of life throughout dialysis therapy. Integrating ONLINE HDF as a standard feature of the 5008 advanced therapy system mimics even more closely the bodys natural renal function. 1. Canaud B, Morena M, Leray-Moragues H, et al. Overview of clinical studies in hemodiafiltration: what do we need now? Hemodial Int. 2006; 10 (Suppl. 1):S5S12. 2. Altieri P, Sorba GB, Bolasco PG, et al. On-line predilution hemofiltration versus ultrapure highflux hemodialysis: a multicenter prospective study in 23 patients. Sardinian Collaborative Study Group of On-Line Hemofiltration. Blood Purif. 1997; 15:169181. Fresenius Medical Care Asia Pacific CDPB112013
60
ON-LINE HEMODIAFILTRATION Clinical Issues Despite significant advances in the treatment of HD in recent years, morbidity and mortality among HD patients are still unacceptably high. There are number of reasons for the poor patients outcomes: Patient characteristics, particularly advanced age and co-morbid conditions The limitations of the artificial replacement therapy - partially able to substitute the natural kidney functions o Conventional HD prescription is far from being optimal, providing only about 10% of the clearance power of the natural kidneys
ONLINE HDF
Patients groups could benefits from ONLINE HDF
Patient with anemia & hyporesponsiveness to EPO Patient with difficult control of hyperphosphatemia
Patient with residual renal function
ONLINE HDF
Patient with intradialytic hemodynamic instability Patient with MalnutritionInflammationAtherosclerosis (MIA) syndrome
Patient at risk of B2microglobulin-related amyloidosis
Patients with intradialytic hemodynamic instability The most common explanation given for the improved cardiovascular stability of patients treated with ONLINE HDF are the removal of potentially vasodilating mediators and the cooling of the blood via enhanced thermal energy losses within the extracorporeal system.
Patient with Malnutrition-Inflammmation-atherosclerosis (MIA) syndrome) Chronic inflammation involves a complex circle of various protagonists (main cause). E.g. advanced glycation end product (AGEs), abnormal lipoproteins and oxidative stress. They are classified as non-traditional, uremia-related and dialysis-related factors, and are linked to each other resulting ultimately in endothelial dysfunction, which is one of the early events in the progression of atherosclerosis. In addition, inflammation not only is associated with progressive atherosclerotic cardiovascular disease but also with malnutrition constituting (a part) the MIA
CDPB112013
61
syndrome. Thus, prevention of inflammation is now regarded as one of the principal targets of therapy for reducing the incidence of MIA-related complications in long-term dialysis patients. By means of increased corrective removal of larger molecules, ONLINE HDF may contribute towards the suppression of the vicious circle of the MIA syndrome, in conjunction with highly biocompatible membranes and dialysate. Patient with anemia and hyporesponsiveness to erythropoietin Besides a higher removal of erythropoiesis-inhibiting substances, another factor which may also account for the positive effect of ONLINE HDF treatments on anaemia correction is the optimal microbiological quality of the dialysate. This leads to reduction of the chronic inflammatory state, with consecutive improved iron utilisation and reduced resistance to erythropoietin. Patient with difficult control of hyperphostemia Although adequate removal of phosphate is limited by its complex multicompartment kinetics, the long-term use of ONLINE HDF, especially in association with an extended treatment time, may nevertheless allow a reduction in the amounts of phosphate binders prescribed.
Patient at risk of B2-microglobulin-related amyloidosis Several prospective, controlled studies have confirmed that the enhanced convective removal of B2-M by HDF was accompanied by a significant decline of blood B2M concentrations.
Patients with residual renal function The treatment of HD patients with high-permeability, biocompatible membranes and ultrapure dialysate, as offered by ONLINE HDF therapy, has been reported to slow the decline in RRF.
Clearances with Different Modality

Clearances, 300 250 200 150 100 50 0
100 101 102 103 104 105 106 107 HD High Flux High Flux HF High Flux ONLINE-HDF Inulin Albumin ml/min. UreaCreat Vit B12 2M
Glomerular Filtration
Mimic the Kidneys
Molecular Weight, Daltons
CDPB112013
62
HDF treatment modalities are classified according to the administration of substitution solution:
Substitution Solution
HDF treatment modalities are classified according to the administration of substitution solution: 1. Post-dilution: The substitution fluid is administered after the dialyser to replace the filtrate being removed (e.g. close to venous chamber) 2. Pre-dilution: The substitution fluid administered to pre-dilute the blood before its passage through the dialyser
Pre-dilution
Post-dilution
Hydraulic
Extracorporeal Circuit
Recommended Exchange Volume

The following exchange volume are recommended for given effective blood flow and dialyser type in order to achieve high efficiency HDF
CDPB112013
63
Best Practice Guidelines Recommendation to Improve Patient Outcomes

The recommended water quality standards
ISO Standard for HD Fluids (ISO 26722: 2009) Type of Fluid

HD Water Dialysate On-Line Substitution
CFU/ml
100 100 Sterile
EU/ml
0.25 0.5 Non-pyrogenic
Safety and Reliability of the dialysate ultrafiltration is ensured by redundancy of filters, which permits to increase the probability rate. This concept is illustrated above. In this example, we compare the probability of success and failure of sterilizing fluid solution when comparing 1 ultrafilter versus 2 ultrafilter disposed in series. Assuming the use of a single ultrafilter with a 99.9% nominal retentive capacity to sterilized contaminated dialysis fluid solution containing 106 bacteria/ml, the probability of having bacteria passing through the membrane is in this case 0.1%. In other words, for bacteria present in the incoming fluid, the chance of crossing the membrane is estimated at 10-4. If a second ultrafilter, featuring the same characteristics, is interposed in series on the dialysate line, applying the same reasoning to two ultrafilters in series, the probability for a bacteria passing through the second filter is now reduced to 0.0001%. That means that for each bacterium present in the upstream fluid, the chance of crossing the membrane is now reduced to 10-8. For optimal safety, it is therefore obvious that the implementation of ultrafilter in series is the best option to reduce probability of failure. Practically, two ultrafilters in series appears to be the best cost/effective ratio to produce economic and safe ultrapure dialysate for routine dialysis.
Safety and Reliability of the ultrapure dialysate

Retention Capacity 99.9% for bacteria count <106
Affluent Permeate Permeate
Probability 100% 0.1% 0.001%
1 Bacteria
10-4 Bacteria
10-8 Bacteria
First Filter Stage
Second Filter Stage
CDPB112013
64
Considerations for OL-HDF

Parameter
Qb Qd Qs
Action
Qb < 300/350 Pre dilution Qbw
Rationale
Prevent fouling of membranes due to FF% > 50%. Plasma water is only component available for convection Therapy not dependent on diffusive (high convective component) Use OCM to monitor
Autoflow 1: 1.5 (Qb: Qd)

AutoSub Mean 50 mls/min
IDFG < 3% EDW
Fluid management As per usual dialysis management but degree of difficulty Dt Anticoagulation Dialyzer/filter
Usually 4 hours but dependent UFR, Qs & OCM High risk ? Predilution Review Hct & TP & risk on
Predilution 1:2/3 1:1 Qb:Qs Post dilution 25 - 30% Qb
fouling of membranes related to patient factors and Qb related Qs KuF
FX series FX 60 or FX80
Why OL-HDF?
Hemodiafiltration
ONLINE-HDF
Nearer to the Real CONVECTIVE + Thing Diffusive
CDPB112013
65
Clear Medical Advantage

Improved Dialysis Dose Improved Lipid Profile Reduce Intradialytic Symptoms Reduce Number of Hospitalization
Ca x PO4 Equilibrium Reduce EPO Requirement Lower Mortality Rate Improved Nutritional Status
Lower Arterial Pressure & Less Antihypertensive drugs Reduction Oxidative Stress Better Removal of -2m Better Removal of Phosphate
Better Management Hypotension and Hypertension
NOTES Fresenius Medical Care Asia Pacific

CDPB112013
66
CANNULATION: IMPROVING THE FUNCTION & SURVIVAL OF VASCULAR DIALYSIS ACCESSES Cannulation is critical component of the dialysis procedure. If cannulation is unsuccessful or not effective this results in inadequate dialysis. From the patients perspective the pain associated with cannulation at least three times a week can become a major stressor and affect negatively psychological well-being. There is also a sense of continual fear and unpredictability for the patient regarding the cannulation of the vascular access. Nephrology and medicine has overall advanced in many facets of care but some areas of practice remain rudimentary and cannulation is one area of practice that lags behind the other technologies. Since the early days of chronic hemodialysis, the cannulation procedure has not dramatically changed and success depends primarily on the skill of the nurse and the viability of the vascular access. Discussion on a resurrected technique Constant site Button hole is presented in the last segment of this section, and offers some hope in resolving the unpredictability and pain associated with cannulation. Some attention has been directed and the development of the vascular access by planned site cannulation. Thereby the nurse needs to view cannulation in both the short and long term, with success of needle placement today as well as cannulating the access in order to develop the vessel to prevent stenosis and aneurysms. See Figure 1.1.1.4.
www.medisystems.com:
This site provides videos on Dialysis Vascular access (AVG, AVF, Monitoring systems) and cannulation techniques (Including Button hole). Deborah Brouwer RN CNN (Nurse on the KDOQI CPG Vascular accesses committee) demonstrates the assessment and cannulation procedures. These videos also highlight the lack of available evidence for cannulation technique, with discussion regarding the direction of the bevel entry with mainly anecdotal dialogue.
CDPB112013
67
Activity 1: Develop a cannulation plan that is designed to achieve the following: Increased survival of access; reduced complications of aneurysm and stenosis. Ensures safety for Nurse and Patients. Also identify the gaps in available evidence to support practice. Are you able to answer the practice queries of bevel up or down, rotation of needle, arterial needle position requirements. There remains a lot of folklore in cannulation practice a blown needle site is good for development of the vessel How would you address correction of the culture to one of more EBP? MEASURING AND MONITORING VASCULAR ACCESS FUNCTION AND BLOOD FLOW. For optimal clearance by the hemodialysis procedure, placement of cannula and diameter size relative to blood flow (Qb) is critical. Usually cannulation is commenced with smaller gauge needles (16-17G) and as vessel develops together with the need to increase Qb to advance dialysis adequacy. Related to physics and fluid flows, if the Qb is increased > than the diameter of the cannula, turbulence is created and possible damage long term to vasculature. Thereby if required Qb > 350 mL/minute needle cannula size of > 15 G is required, necessitating a well-established vessel structure. The measurements required to ensure vascular access patency and early detection of changes requiring intervention include: Access recirculation www.kidney.org/professionals/kdoqi/guidelines_updates/doqiupva Vascular access blood flow calculation; See Figure 1.1.1.4.2 - Krivitskis Method of Blood flow measurement. The Fresenius BTM is a useful tool to estimate blood flow and recirculation. Figure 1.1.1.4.2 MEASUREMENT STRATEGIES FOR VASCULAR ACCESS BLOOD FLOW
Care:
Activity 2: Incorporate vascular access effectiveness measurements into your Plan of - Type of measurements, frequency and criteria for assessments.
CDPB112013
68
THE CONSTANT SITE TECHNIQUE (BUTTON-HOLE) With the advent of enhanced therapies, inclusive of daily more frequent dialysis there was a need for more a cannulation technique that coped with the increased frequency of cannulation without harm / complications. Kronung and Twardowski have both been instrumental in the resurgence of the Constant site (A.K.A. Button hole). There has been reported success in the programs utilizing this method, but is reliant on the following attributes of the dialysis program and practice: Assignment of primary nursing, same nurse patient, to facilitate the development of sites for cannulation; KNOW THE ACCESS Stable staffing in the dialysis centre. Once established venous and arterial sites identified and developed, use of blunt, nonsiliconised cannula. Monitoring the effectiveness of this cannulation technique long-term.
DVD PATIENT INTERVIEW AND DEMONSTRATION OF CANNULATION TECHNQIUE Activity 3: What further information would be required before you would implement the buttonholer procedure in your Dialysis program? How would you implement the button-hole technique into your dialysis program safely and effectively?
PERCUTANEOUS DIALYSIS CATHETER CARE AND MANAGEMENT These catheters are fraught with many practice issues, and there are various methods that are used with their management. Like cannulation technique there is a need for some multicentre, longitudinal studies to be implemented to assist in EBP. The main issues relate to reducing infection, catheter exit site care, improving survival and patient satisfaction comfort. However the RR of death is markedly increased and associated with the use of CVDC. Fresenius Medical Care Asia Pacific
CDPB112013
69
NOTES CDPB112013 Fresenius Medical Care Asia Pacific
70
PERITONEAL DIALYSIS There are some early references to use of the peritoneal cavity for therapeutic purposes. The above is an example: an interesting if somewhat wasteful use for red wine. Its also an extreme example of bioincompatibility of peritoneal fluids the wines action was almost certainly to obliterate the peritoneal cavity through induced fibrosis. There are also reports of the peritoneal cavity being used as a method for delivery of fluid to the body at a time when i.v fluid administration was unknown attempts were made to replace fluid loss in cholera cases by the transperitoneal route.
Phy siologic Milestones

1862 von Reck inghaussen Description of the gross and cellular anatomy of the peritoneum Peritoneal lavage in dogs Effects of fluid temperature on sy stemic temperature Osmotic ultrafiltration Peritoneal mass transfer Effect of PDF tonicity on ultrafiltration First comprehensive description of peritoneal mass transfer, diffusion and osmosis
1877 Wegner
1894 Starling & Tubby
1922 Putnam
The first description of the gross and cellular anatomy of the peritoneum was provided by Von Reckinghaussen in 1862. Shortly afterwards, Wegner infused cold saline into the peritoneal cavity of dogs and observed a fall in body temperature. When hypertonic glycerin or dextrose was used, water moved into the peritoneum, perhaps the first evidence of osmotic ultrafiltration. Starling and Tubby expanded these observations by studying the bidirectional transfer of molecules across the peritoneal membrane and demonstrating the rapid absorption of isotonic solutions and slow absorption of serum. In 1922, Puttman provided the first comprehensive description of peritoneal mass transfer, diffusion and osmosis, concluding that mass transfer was driven by passive concentration gradients diffusion - rather than active membrane transport.
CDPB112013
71
Anatomical and Physical Basis Of PD
The external landmarks of the peritoneal cavity seen from the front are approximately as shown by the thick red line. The peritoneal cavity is entirely within the abdomen. Removing the anterior abdominal wall we see the arrangement of the intra-abdominal organs. The organs are relatively tightly squeezed within the abdominal cavity. The shiny surface seen on the intestines and other organs is the peritoneal membrane which also lines the inner wall of the abdominal cavity.
Peritoneal membrane
visceral peritoneum parietal peritoneum
The peritoneal membrane lines the inner wall of the abdominal cavity and the organs contained within the abdomen. Its primary function is to provide a lubricated surface for mobile organs within the abdomen thus preventing friction. The membrane is formed of a layer of cells - mesothelial cells - supported by a thin membrane and by connective tissue. Within the connective tissue lies a network of blood vessels which derive their blood from the aorta and branches and return blood either directly to the inferior vena cava or through the circulation of the liver to the portal vein. Fresenius Medical Care Asia Pacific CDPB112013
72
The peritoneal membrane is continuous in males but discontinuous in females in whom there is a potential connection with the genital tract. The cavity formed by the peritoneal membrane normally contains less than 100 ml of a special lubricant fluid which is secreted by the mesothelial cells. A few cells which are related to white blood cells - resident peritoneal monocyte-macrophages - provide initial defense against peritoneal invasion by bacteria. Additionally, the peritoneal fluid contains some large proteins - immunoglobulins and opsonins - which also serve a defense role against infection. The total surface area of the membrane is between 1 and 2 m2 with most of the surface area covering intra-abdominal organs (80% visceral p) and least covering the interior abdominal wall (20% parietal p). The estimated blood flow rate through the peritoneal vascular network is between 60 and 100 ml/min. The peritoneum is also liberally supplied with another network of vessels known as lymphatics. Secreted peritoneal fluid is reabsorbed through these into the circulatory system; the lymphatic circulation is an additional component of effective local host defense.
The Peritoneal dialysis system

Peritoneal dialysate
Visceral peritoneum Intestinal Loop Intestinal Loop capillaries
Intestinal Loop
Intestinal Loop
Visceral peritoneum
Peritoneal dialysate
If we take a small segment of the abdominal cavity in cross section we can visualize a number of the loops of intestine crowded together. Each loop is attached to its mesentery, a double layer of the peritoneal membrane and this membrane encircles the intestinal loop and is highly vascularized as shown. If we fill the peritoneal cavity with a few liter of peritoneal fluid we see the intestinal loops with their peritoneal membrane and mesenteries float in the fluid as suggested above. You now have a situation where a fluid is separated from the patients flowing blood by a complex membrane partly the wall of the vessel and partly the peritoneal membrane. We have a system where blood is separated by a membrane from a solution: we have a system where processes such as solute diffusion and convection and water osmosis can occur.. We have a potential dialysis system. The arrangement of the peritoneum and peritoneal cavity obviously did not evolve to be a dialysis system it is simply that a certain arrangement of blood vessels in the body (the peritoneal vascular network) is conveniently organized to present the opportunity for a dialysis system.
CDPB112013
73
One theory described to explain the way that solutes and water are transported during peritoneal dialysis is the nearest vessel concept. As shown in the cartoon, some vessels are nearer to and others further from the peritoneal fluid. As well as being anatomically variable, peritoneal blood vessels will also vary in terms of whether or not they are perfused with blood; not all vessels will receive an equal flow of blood at all times. Distance between blood and dialysate will obviously affect osmotic and solute concentration gradients and therefore affect rates of solute and water flux. Without delving into excess detail regarding the theories of peritoneal membrane function it should be appreciated that, compared to the inert membrane and geometry of an artificial kidney dialyzer, the peritoneal dialyzer is highly complex and its solute and water transport functions cannot easily be precisely predicted.
Detailed analysis of water and solute transport during peritoneal dialysis suggests that the peritoneal dialyzer functions as if there were three populations of pores in the membrane. A small number of large pores which are probably intercellular gaps between endothelial cells transmit large molecules such as proteins.
CDPB112013
74
Small pores transmit solutes in the small to middle-molecular size range and ~40% of water transport is through ultra-small pores which are transcellular channels. The concept is represented by the cartoon above. The concept is functional rather than anatomical. The flux of water through ultra small pores which provide near complete resistance to diffusion and convection of even small solutes explains why glucose, a small molecule of 180 Dalton is so effective an osmotic agent. In effect, the ultra small pores bring the peritoneal membrane nearer to the function of an ideal semipermeable membrane.
Native blood supply to and flow through peritoneal vessels

blood dialysate
Dialysate delivery and exchange system
Membrane that separates blood and dialysate and supports solute and water flux
It seems almost too good to be true. The body provides us with two of the requirements for a dialysis system the membrane and a continuous flow of blood through native blood vessels in close proximity to the membrane. All we have to do to complete a dialysis system is provide a system for delivery of a dialysate. When the modern era of PD commenced with the description of CAPD it was believed that PD would find its true place and value in dialysis for ESRD. It had many advantages over HD no machine (or for APD a simpler device than for HD); no issues related to membrane bioincompatibility; continuous versus intermittent treatment etc. etc. Many anticipated that application of PD would equal or exceed the use of HD and, in fact, for a while during the 1980s PD as CAPD (and APD to lesser extent) did reach utilization rates of ~ 50% of all dialysis is some countries.
CDPB112013
75
Access to the Peritoneal Cavity An important starting point to this discussion is to remind that the intact skin is a critically important barrier preventing access of pathogenic organisms (viruses, bacteria, fungi, parasites etc.) to the internal tissues and organs of the body. In a real sense, the skin (and the mucous membranes lining the intestinal, pulmonary and urogenital tract) is the first line of defense against infection and infestation. Peritoneal Catheters
The most important development in PD catheters is attributable to Tenckhoff and one or other variant on the Tenckhoff catheter accounts for >99% of catheters used in modern PD. In 1968, Tenckhoff and Schecter revolutionized the field of peritoneal dialysis and introduced a permanent catheter and a method of implantation that for the first time allowed relatively long periods of usage with a significant reduction of infections. An important feature of the design was the inclusion of two Dacron felt cuffs which would seal the inevitable tunnel through the layers of the abdominal wall that resulted from catheter placement. Tenckhoff also proposed the use of a semiarcuate tunnel with a downward exit to reduce accumulation of debris and to minimize infection. Tenckhoff H, Schechte H. A bacteriologically safe peritoneal access device. Trans Am Soc Artif Intern Organs 14:181-186, 1968 Catheter Variants Catheter Features
CDPB112013
76
Catheters are not one size fits all for obvious reasons. They come in various sizes to fit the needs of small children on up to extra large adults. For any size it is also important that the segment dimensions particularly the length of the segment between the Dacron cuffs is appropriate to the thickness of the abdominal wall and that the intraperitoneal segment is neither too short or too long. For obvious reasons the internal diameter of the catheter must be adequate to permit a fast flow of PD fluid without requiring a large pressure head: for CAPD the pressure head is simply gravity. Rate of flow is also related to the perforations of the intraperitoneal segment. The idea of the coil at the end of the catheter shown upper above is twofold to help the catheter to stay in the pelvis and to increase the total number of perforations without having an excessively long straight intraperitoneal segment which could get entangled with bowel loops. Silicone which is the basic material of catheters has a memory. It will always seek to reassume the structure and shape in which it was manufactured. As we will see, when the catheter is placed in the abdominal wall its tunnel is curved. If the catheter was manufactured straight it will try to overcome the curve and will, over time, actually push itself out. This can be overcome by making the catheter with a fixed curve (below panel above) called a Swan-neck. There is very little evidence that the variants make much difference although the Swan-neck variants seem to be becoming increasingly popular. Catheter Placement It is critically important to catheter function and to its trouble free and preferably prolonged residence that its placement be undertaken with care. One approach is to undertake open surgery of the abdomen but this is a major surgical procedure and involves considerable trauma to the abdominal wall and to the peritoneum. Modern catheter placement seeks to minimize surgical trauma whilst ensuring proper placement of the catheter intraperitonealy and achieving a passage through the abdominal wall that forms an effective barrier 1) to access to bacteria etc. and 2) seals (or reseals) the peritoneal cavity against fluid leakage to the exterior.
CDPB112013
77
Remembering the importance of an intact skin to prevention of infection, the major risk area for catheters is the exit site and the tunnel where the catheter penetrates the layers of the abdominal wall. Obviously the skin is broken where the catheter exits. Normally a wound of this sort would completely close and heal restoring the integrity of the skin barrier. This healing is incomplete when there is a permanent foreign body such as the catheter present. The resultant failure to reestablish a fully normal skin layer here predisposes to infection. Note the position of the Dacron cuffs. One is placed and secured just inside the skin exit site and the other is secured deeper in the muscle layer. The Dacron cuffs actually encourage a vigorous inflammatory response whereby fibrous tissue grows into the cuff material and forms a bond with the surrounding tissues. We now have a sealed tunnel through the abdominal wall between the cuffs. There is potential for a closed infection (an abscess) to form in this tunnel. Inside the abdomen the catheter tube is related to loops of intestine and to the apron-like omentum which hangs between the abdominal wall and the intestinal loops. The inner part of the catheter is not fixed in place and can migrate out of the pelvic cavity which is the preferred site for optimum function. The catheter, being a foreign body, also elicits some inflammatory response so that it may become attached to and surrounded by intestine or omentum effectively blocking its pores and flow of fluid. These factors have to be considered in catheter insertion and placement.
cuff extrusion
catheter migration
Other problems that may result from improper catheter placement are indicated here. For straight catheters the silicone memory results in a chronic sustained pressure on the curve of the catheter in the abdominal wall. Ultimately this may force the catheter straight and the subcutaneous cuff is then extruded outside the tunnel. This greatly increases the risk of exit site and tunnel infection. The other problem is that since the catheter is not fixed internally, it may migrate out of the pelvis. The migrant catheter is more likely 1) to get entangled in bowel or omentum and therefore blocked and 2) may come to lie high in the abdomen where it does not enable proper drainage of the intraperitoneal fluid.
CDPB112013
78
Catheter problems and PD failure

28% 18%
Psychosocial
Catheter etc
Peritonitis Other medical
Inadequate Dialysis
15% 14%
25%
The drop out from PD to HD exceeds 10% of prevalent PD patients per year: the drop-out in the other direction is < 1%. Drop out is treatment failure and where the patient has then to move from independent, home- and self-care to in centre HD that is a major and often undesired change for the patient. Approximately 30% of PD failure and drop out is somehow related to unmanaged or unmanageable problems with the catheter or the exit site. It is reasonable to surmise that a majority of these drop outs could be prevented by proper attention to detail of care starting with the preparation for catheter placement, through placement and on to post-placement care. PD Access and Connect Systems
Single bag wearable PD systems
to catheter
transfer set frangible safelock
When Popovich and Moncrief first described CAPD in 1976 PD solutions in the USA were available only in bottles: PVC bags were not approved by the FDA. The method they described involved filling the peritoneum from a cold of liter bottles of PD fluid, detaching from the bottles when fill complete and then when drain was to be initiated reconnecting to the then empty bottles.
CDPB112013
79
The bottles had to be spiked with large bore needles attached to the tubing (giving) set. This step posed great risk of touch contamination from bacteria on the hands. Since each exchange involved four spiking the risk was very high and the peritonitis rate reported for these early days of CAPD was as high as 1 episode per 8 weeks. (A peritonitis rate of 1 per 80 weeks would now be considered a high rate.
Y set flush before fill
contamination
2 fill
Y connect
1 flush
Touch contamination of the connection between transfer set and the bag remained a problem despite developments such as the safe-lock. There were even devices developed to attempt to kill any bacteria that might contaminate the connection e.g., the Baxter UV-Flash device. The Italians provided an answer. Bazzato visualized that any bacteria in the connection would necessarily be transported in the inflow straight into the peritoneal cavity. Even one or two bacteria could then establish colonies in the peritoneum and lead to peritonitis. His idea was wonderfully simple. Create a system for two flow paths using a Y connector on the giving set. Then, before filling the PD fluid into the peritoneum, flush the initial flow from the recently made connection to the bag down a separate tube and away from the peritoneum. After this flush which he had shown did indeed remove contaminating bacteria from the upper tubing nearing the connection to the bag, redirect the flow to the peritoneum. The different flows were controlled by clamps. In early reports the Y system reduced peritonitis rates by ~ 50%. In early systems the bags and Y set were separate but later became joined in the various double-bag systems.
CDPB112013
80
Double-bag CAPD systems
Baxter Ultrabag
Fresenius A.N.D.Y
Gambro Gemini
The next step was to integrate the PD fluid bag with an attached Y-set which was in turn attached to a drain bag. Examples from the three main companies are shown above. All systems involved the patient in learning a number of procedural steps that required to be performed in a certain order mainly to ensure flush before fill. There remained the need to connect these systems to the transfer set still a potential site of touch contamination. With double-bag systems peritonitis rates were as low as or slightly better than with the detached Y set. A sort of bench-mark emerged: that peritonitis rate should be less than 1 in two years. Centers of excellence could achieve rates less than once per 36 months.
The disc flow controller stay safe
The disc (flow direction controller) of the staysafe system (and others including ANDY.disc and balance etc.) was created to make easier the patients procedural steps in double bag systems and to enforce the flush before fill. Fresenius Medical Care Asia Pacific
CDPB112013
81
Instead of clamps on lines which had to be opened and closed in a correct order, flow direction control was enclosed in a disc device where turning a handle opened or closed the flow channels. An additional feature was a pin with sealing O ring that was ejected by the disc at the last step and sealed the transfer set. PD Solutions In many respects the PD solutions perform a similar function to dialysate in HD. The big difference is that in PD ultrafiltration has to be achieved by osmosis rather than hydrostatic pressure necessitating that PD fluid has a higher effective osmolality than plasma water (in Extraneal the effect is more an oncotic effect). The sodium concentration of PD fluids also tends lower than used in standard HD: this is ensure adequate sodium removal since some 40% of the fluid removed by osmosis (that through aquaporins) is hypotonic for sodium and must be compensate by extra sodium diffusion across small pores down a concentration gradient.
Conventional PD fluids
Novel PD Fluids The novel solutions can be divided broadly into: 1) PD fluids containing amino acids 2) PD fluids with an alternative to glucose for ultrafiltration and 3) PD fluids with reduced GDPs. Additionally, there is current interest in the possible application(s) of PD fluids with lower sodium concentration. Amino Acid PD Fluids AA as alternative osmolyte AA for delivery of nitrogen and improved protein nutrition Fresenius Medical Care Asia Pacific
CDPB112013
82
Alternative Osmolytes Suggested alternatives to dextrose Amino acids Peptides Glycerol Albumin Glucose polymer (polyglucose: icodextrin Reduced GDP Fluids lactate based Mixed buffer lactate and bicarbonate Physioneal - Baxter development product - Gambro Solo bicarbonate buffer bicavera - FME
PD fluids other variants

Hypotonic
0.5% dextrose
Variable calcium concentration

High Low Range 1.75 mmol/L 1.25 mmol/L 120 130 mmol/L
Low sodium dialysate (development)
PD Complications One of the lessons of in PD was that problems with catheter and exit site were not simply issues that needed treatment but that the problems could lead to a complete failure of the PD modality (and therefore need to transfer to another modality usually in-centre HD). The focus on complications will be peritonitis. Again we will see that in PD these complications not infrequently result in modality failure. This results in the phenomenon of drop-out which in most PD programs contributes more to loss of patients from the modality than does death (or transplantation). We will finish this module with some insights into the dynamics of drop-out. Peritonitis The suffix itis in medical terminology indicates inflammation e.g., arthritis, vasculitis etc. An early marker of inflammation (itis) is accumulation of blood and tissue cells at the site of inflammation. These are mainly from the white blood cell families such as polymorphonuclear granulocytes, monocytes and lymphocytes and their normal function is to initiate a cascade of events that remove/eradicate the cause of the inflammation, e.g., bacteria. When the cell count in an otherwise clear fluid increases (> 100 cells per L) the fluid becomes turbid or cloudy. The inflammatory response is usually but not invariably associated with pain and may induce a febrile reaction (rise in body temperature). Fresenius Medical Care Asia Pacific
CDPB112013
83
In PD peritonitis is such a reaction leading to cloudiness of the PD effluent and may be accompanied by pain and fever. Although some or other form of infection is the more common cause of peritonitis, the itis may be a response to a chemical agent; for example, chemical peritonitis is known to occur with time-expired PD fluid and also, in some susceptible patients, with icodextrin (Extraneal). Infective peritonitis is usually bacterial but may be due to fungi. The commonest bacteria causing peritonitis are from the staphylococcal family and usually indicate contamination from the exterior: the staphylococci stain positively with the Gram stain and can further be classified by whether they do or do not exhibit the coagulase antigen (S. aureus is coagulase positive and S.epidermidis is coagulase negative). Bacteria that do not show positive with the Gram stain are more likely to be from and endogenous source the blood stream or the intestinal or urogenital tracts and include E.coli and pseudomonas. In a significant minority of cases of what are almost certainly bacterial infections attempts to culture the organism in the lab fail and these events are described as culture negative peritonitis.
Routes of entry for microorganisms
Touch contamination
transmural
biofilm
Remember that the peritoneal cavity is a cavity or space within the abdominal cavity and is completely closed in the male but is potentially connected to the genital tract in the female. When a peritoneal catheter is in place the peritoneal cavity is open. The easiest and most common way for bacteria to enter the cavity is via the catheter and therefore from the PD system. The usual cause of this is failure of technique whereby the patient or operator contaminates the system during the process of bag-system exchanges: this is generally called touch contamination. The more likely organisms associated with touch contamination are those that commonly reside in skin (S.epidermidis) or the nose (S.aureus). Another possible route is from the exit site via the catheter tunnel transmural infection and there is a well known increase in risk of peritonitis in patients with exit site or tunnel infection. It is also possible for bacteria to migrate from the intestinal or genitourinary tracts when infection is more likely to be associated with gram negative bacteria found in great abundance in these sites.
CDPB112013
84
As we explained in a previous module about water treatment for dialysis, bacteria can occur in two forms planktonic (free floating) and sessile (attached). The initiation of a peritonitis is certainly likely to be related to introduction of bacteria in planktonic phase via the connect system. Once the bacteria proliferate in the peritoneum they are highly likely to attach to the catheter material and take on a sessile existence as biofilm. As such they may be difficult or impossible to eradicate and are likely to repeatedly and intermittently reinfect the peritoneal cavity. This emphasizes the importance of early aggressive treatment of infection before the bacteria can transform into biofilm. In many large reported series of PD patients between 50 and 80 percent of PD patients never experience an episode of peritonitis. We have to conclude therefore that a minority of patients suffer a majority of infections. This should alert us to an important insight which is that the patient-system interface is almost certainly more important than the system alone. Probably the most important patient factor is their strict adherence to guided technique and hygiene (although there may also be other factors such as innate host defense etc which alter the risk of peritonitis developing from a bacterial contamination). None would argue that the most important strategy for prevention of peritonitis is patient training and retraining in proper technique of fluid exchanges and care of the exit site. Other preventive strategies have been proposed e.g., that nasal carriage of S.aureus (staff and patients) be actively managed. Early detection and initiation of treatment is desirable and again depends upon patient education regarding self-diagnosis and patient willingness to seek early medical attention. Antibiotics given both intraperitoneally and systemically are the mainstay of treatment and there is a constant debate regarding which are the most effective first line antibiotics. Antibiotic resistance and particularly the emergence of super-bugs (multiply resistant bacteria) is becoming a significant issue in PD. Additionally, there is a significant and increasing rate of infection relapse and recurrence which may well be related to 1) antibiotic resistance and 2) biofilm on the catheter. In many cases the catheter has to be removed and replaced with a new one not a minor procedure.
M anagement of peritonitis
Prevention Early detection and initiation of Rx Antibiotics
Intraperitoneal and systemic
Which most effective 1st line?
Resistance, relapse, recurrence Catheter replacement Modality change

Temporary Permanent Role of biofilm
Repeated peritonitis and relapse and recurrence may indicate the need for a change of dialysis modality. This might be temporary, either to allow the peritoneum to settle down or for patient retraining and reevaluation but often peritonitis is the immediate reason for abandoning PD completely and transferring the patient to hemodialysis.
CDPB112013
85
The CAPD concept

Equilibrium concentration
Curea = 100 mg/dL Gurea = 7.6 mg/min Volume = 8 L Volume = 8 L Curea = 100 mg/dL Kurea = 3 mL/min Mass = 8,000 mg Curea = 0 mg/dL
Equilibrium diffusion
Daily generation = 10,880 mg Daily excretion = 2,880 mg Retention = 8,000 mg
The original description of the concept of CAPD by Popovich and Moncrief is summarized here. They envisaged a patient with a certain body water volume and urea generation rate derived from a protein intake of ~ 1 gram/kg/day. Their original model allowed for no renal function but in this case I have shown a residual renal urea clearance of 3 mL/min which would be fairly common in a patient starting PD treatment. From calculations we learnt in earlier modules we can estimate that this patient is generating 10.9 gram urea per day, excreting 2.9 g per day and therefore retaining ~ 8 gram per day. Their idea was to describe a dialysis that would remove this 8 g in a day and therefore maintain a constant serum urea concentration of 100 mg/dL. Their calculations indicated that a volume of dialysate of 8 to 10 Liter that was allowed to reach diffusion equilibrium concentration with blood would remove the retained urea and so maintain a constant blood and body urea mass and concentration. From the available knowledge of the capacity of the peritoneal cavity and the approximate rate of solute diffusion across the peritoneum they proposed that 4 or 5 exchanges of 2 liter of peritoneal dialysate per day would do the trick. CAPD is equilibrium dialysis in two senses. It is based on diffusion to equilibrium concentration in the peritoneal cavity and it achieves near equilibrium concentration for body solute mass and concentration. It seems so simple but this was a revolution: prior use of PD as IPD which did not achieve solute equilibrium required more than 30 liter of dialysate to achieve the same solute removal. Unlike IPD, to require only 4 or 5 exchanges of 2 L per day could readily be performed by the patient and away from the hospital ward. Thus was born CAPD.
CDPB112013
86
Solute clearance
5.5 mL/min At equilibrium clearance equals dialysate flow rate
100 mL/min
CSOLUTE 1.0 mg/mL
CSOLUTE 1.0 mg/mL
5.5 mL/min
When we examine solute exchange in HD changes happen relatively quickly and changes in solute concentration are quite large. By contrast, in CAPD everything happens very slowly and changes in solute concentration (and volume flow) are very small when examined on a minute to minute basis. If we apply the known equations for clearance and where during an exchange of PD fluid solute concentration equilibrium is reached then the solute clearance is equal to the dialysate flow rate. The calculations are much easier than those we examined for HD. The important message here is that in CAPD solute clearance and therefore mass of solute removed is virtually completely dependent upon dialysate flow rate which is the total volume of dialysate drained from the peritoneal cavity. It does not make sense really to express solute clearance on a minute by minute basis as we do for HD. We express it per day or even per week. For the above example CAPD with 8 liter drainage per day would yield a urea clearance of ~ 55 L per week. Standard high efficiency dialysis (thrice 4 hours per week) with a dialyzer Kurea of 280 mL/min would yield a weekly urea clearance of ~ 200 L per week. CAPD seems very inefficient by this measure. The CAPD regime would remove ~ 55 gram of urea per week. Although the HD appears much more efficient each dialysis session would actually remove only about 20 g urea or 60 gram per week so not really very different. (for revision refer to the module on Solute Kinetics in HD) Moreover, the body urea concentration for CAPD would be near constant at ~ 100 mg/dL whereas for the HD patient it would oscillate between high values > 140 mg/dL and low, post dialysis values of ~ 30 mg/dL.
CDPB112013
87
Resistance to diffusion in peritoneal dialysis

mesothelial cell blood vessel
vessel wall dialysate tissue matrix
blood flow
When we examine a section of the peritoneum and the relationship of the blood flow to the dialysate flow channels there appear to be many possible points at which to expect resistance to diffusion of a solute in either direction. For a solute to get from blood to dialysate or dialysate to blood it must cross the vessel wall essentially a layer of endothelial cells then cross the tissue matrix and the mesothelial cells. It must then pass through any resistance posed by the boundary layer of dialysate abutting the mesothelial cell.
Tw o significant resistances to diffusion

diffusion resistance
vessel wall
dialysate boundary layer
In effect there are two significant resistances to solute diffusion. One, and the more important, is the vessel wall and the second is the boundary layer of dialysate that is in contact with the mesothelial cell lining the peritoneal cavity. This seems strange at first when one considers that between the vessel wall and the dialysate there is a significant distance for a solute to travel through a matrix of proteins, connective tissue and cells. The answer lies again with the limitation resulting from the low Qd of < 10 mL/min for CAPD.
CDPB112013
88
Remember that what drives diffusion is difference in solute concentration. In PD the blood flow is more than enough to maintain a high concentration within the blood vessel. However, dialysate flow is slow and at an instant dialysate concentration nearest to the vessel wall will rise fairly quickly and before it can be replaced by fresh dialysate. If we remember Ficks law for diffusion, solute flux was heavily dependent upon concentration gradient and maintenance of a maximum gradient in PD is totally dependent upon dialysate flow. Only if PD were performed with a very high Qd would the tissues between the vessel and wall become a significant point of resistance to solute diffusion. CAPD and Water Convection Unlike in hemodialysis where we can modify TMP by technical means or control ultrafiltration of water from blood by the means of a precise volumetric UF pump, in peritoneal dialysis we remove water from the patient by utilizing the principles of osmosis.
Osmotic for ces in per itoneal dialy sis

70 mOsm 1330 mmHg 1.5% 360 mOsm
290 mOsm
110 mOsm 2000 mmHg
2.3% 400 mOsm
220 mOsm 4200 mmHg
4.25% 510 mOsm
If an average plasma water osmolality of 290 mOsm/kg is assumed we see the osmolality difference dialysate to blood for the three common dialysates with difference ranging from 70 mOsm for 1.5% dextrose to 220 mOsm for 4.25% dextrose. If these osmolal differences were acting across a perfectly semipermeable membrane one that was fully permeable to water but not at all permeable to dextrose huge pressure differences driving water flow would be created and sustained. In fact, a number of factors determine that the full osmotic force is not exerted. The osmotic difference attenuates over the distance between dialysate and the blood vessel wall. In fact, the tissue matrix and connective tissue have considerable capacity to buffer the osmotic effect. The draw of water towards the high osmolality of dialysate dilutes osmolality and reduces osmotic pressure. The osmolyte (dextrose) is not a perfect osmolyte it is absorbed across the membrane from dialysate to blood at least through the small pores. At the aquaporin channel, a near perfect semipermeable membrane exists. Fresenius Medical Care Asia Pacific
CDPB112013
89
UF response to dex trose concentration and variance due to difference in glucose transport
4.25%
IP volume mL IP volume mL
4.25%
1.5%
1.5%
glucose transport = X
glucose transport = 2X
These points are nicely illustrated in this figure taken from a recent paper from Bengt Rippe and colleagues Fluid and electrolyte transport across the peritoneal membrane during CAPD according to the three pore model in Perit Dial Int 2004, 24: 10-27. For those wishing a very detailed knowledge of membrane function this paper is recommended reading. A two liter fill is assumed. In the left panel is the change in IP volume due to ultrafiltration in response to either 1.5% or 4.25% dextrose PDF in a patient with a certain rate of glucose transport across the membrane. Note the higher peak IPV and the later time to peak IPV for the higher concentration dextrose. In this case, by 4 hours IPV is the same as instilled volume for the low dextrose concentration and if the cycle is continued fluid will be reabsorbed from the peritoneal cavity. For the 4.25%, IPV peaks at ~ 4 hours but IPV still exceeds inflow volume at 10 hours. In the right panel, glucose is assumed to be absorbed twice as fast. Peak IPVs are lower and time to peak shorter. Presumably use of a 2.27% PDF would yield intermediate results. Note the fall in IPV once the osmotic gradient is lost. Fluid is reabsorbed from the peritoneal cavity. Most of this reabsorbtion occurs across the peritoneal membrane but some also occurs via flow from the peritoneal cavity through the lymphatic vessels back into the circulation. The mechanics of ultrafiltration and fluid reabsorption will be discussed in greater detail in a module on volume management by PD and include discussion of ways that the membrane fails to provide adequate UF.
CDPB112013
90
The relevance of solute transporter status
We have referred to the dependence of ultrafiltration on the rate of glucose transport from dialysate to blood. Effectively, this is given by the MTAC for glucose. Peritoneal membranes differ between individuals and in the same individuals over time for solute MTAC. High MTAC for one solute such as creatinine will generally correlate with that for another. From the point of clearance of solutes from blood a higher MTAC would seem to be an advantage. However, high MTAC for blood solutes is associated with high MTAC for glucose so that glucose transport from dialysate is higher and the osmolality gradient is dissipated more rapidly; as a consequence ultrafiltration is reduced. The peritoneal equilibrium test (PET) was described as a means of classifying patients into four types according to their overall solute transporter status high, high average, low average and low. An example of such classification based (left) on the D/P creatinine or the D/D0 glucose (right) after 4 hours dwell using a 2.3% dextrose solution is shown above. [the P creatinine is the plasma concentration estimated at 2 hours: the D/D0 glucose is the ratio of the dialysate glucose concentration at 4 hours to that at the start of the dwell and immediately after mixing with any residual dialysate from the previous dwell. In general and for any concentration of PD fluid dextrose, UF achieved will be lower for higher D/P creatinine and for lower D/D0 glucose. Results of the PET might then be used to predict UF and assist PD prescription although it is suggested that more accurate assessments can be made using other tests (e.g., PFT available on POL) APD as Non-equilibrium Dialysis Automated Peritoneal Dialysis is a generic term to describe various PD prescriptions where for all or some of the daily exchanges a device known as a PD Cycler is utilized. The purpose of this module is to provide an adequate understanding of the principles of solute and fluid removal in APD and differentiate these from CAPD. Fresenius Medical Care Asia Pacific
CDPB112013
ultrafiltration
91
APD is the most rapidly growing dialysis modality in many markets. For medical and non-medical reasons physicians and patients are increasingly opting for APD as a first prescription. APD may also be prescribed as a progressive prescription for established CAPD patients where one or other form of treatment inadequacy has developed.
T ypical C C PD-APD cycles

Dry day Wet day
3000
3000
2500
2500
2000
2000
IP volume
1500
IP volume
11:31 16:19 Time 21:07 1:55 6:43
1500
1000
1000
500
500
0 6:43
0 6:43
11:31
16:19 Time
21:07
1:55
6:43
Continuous Cycling PD (CCPD) is the usual term used to describe the prescriptions shown here. The PD exchanges are performed using the Cycler device during a portion of the days 24 hours most commonly overnight while the patient sleeps. The Cycler is programmed for the volume of each cycle and either a total exchange volume or the timing of the phases (fill, dwell, drain) of the cycles and once initiated the exchanges are performed automatically by the cycler. After completion of the final programmed exchange (usually early morning) the cycler may empty the peritoneal cavity, the patient disconnects from the cycler and the peritoneal cavity then remains empty (dry) for the remainder of the day until the next connection to the cycler. Alternatively, the last step in the program may fill the peritoneal cavity after which the patient disconnects and spends the remainder of the day with a full (wet) peritoneal cavity. If one assumes an APD session starting at 10 pm and continuing to 7 am the next day (~9 hours) and 5 exchanges of 2 liter, each cycle will last between 1.5 and 2 hours obviously a much shorter time than the 5 to 8 hours typical of CAPD. As we will see this changes the solute and ultrafiltration dynamics of APD compared to CAPD.
3000
Plus
2500
2000
IP volume
1500
PD Plus
1000
500
0 6:43
11:31
16:19 Time
21:07
1:55
6:43
CDPB112013
92
An adaptation of the CCPD prescription is known as PD.plus as shown above. Either with a dry or wet day (wet shown here) an additional exchange is performed during the early evening. The Cycler can be programmed and enabled to perform this exchange, then disconnected temporarily before being connected again for the typical APD overnight prescription. This method of APD was first described by Jose Diaz Buxo (a physician who now works with FME NA) as a means of increasing the APD prescription/dose for solute removal and/or fluid management without a major increase in cost of fluid. For instance, in the above example, the volume of infused PD fluid above is 14 liter compared to the 12 liters for CCPD with a wet day or 10 liters with a dry day. Clinical evidence has been presented for cost efficiency of this prescription compared to alternatives.
N octur nal Inter mittent PD N IPD

3000 2500 2000
IP volume
1500
1000
500
0 6:43
11:31
16:19 Time
21:07
1:55
6:43
Nocturnal IPD is another prescription programmable on Cyclers. The day may be dry or wet (dry shown here). The NIPD prescription is large total exchange volume (here 16 liter) with short exchanges (here just over an hour per exchange). The NIPD prescription favours high ultrafiltration since the glucose concentration of the PD fluid is repeatedly refreshed before the osmolal gradient has been dissipated. Another form of APD prescription not described further is tidal PD. In tidal PD the peritoneal cavity is not emptied completely between cycles. For example, each exchange after the first fill of 2 liter might be 1 liter, leaving approximately 1 liter in the peritoneal cavity. This shortens the time for fill and drain thus theoretically increasing the dialysis (dwell) time at the same time as maintaining frequent refreshing of the PD fluid and driving forces for solute and fluid removal. In fact, most evidence indicates that the modality is not efficient and is costly. However, it may be the preferred prescription for selected patients.
CDPB112013
93
APD is not equilibrium dialysis

130 120 110
100
90
80
70
60 6:43 11:31 16:19 21:07 1:55 6:43
In discussing CAPD we established the concept of equilibrium dialysis where PD dwell time is adequate to allow near or actual solute concentration equilibrium (equality) for dialysate and plasma and where plasma concentration of solutes is effectively constant. We also established that this fact makes relatively easy calculation for solute clearance where clearance is equivalent or nearly equivalent to the volume of drained PD fluid. This does not apply to APD. In the case shown above we assume a dry day but this would also apply for a wet day since clearance during the long dwell would not be adequate to prevent the rise in concentration of a solute such as urea shown here. The solute (urea) concentration (red) is shown with the APD cycles in the backgound (blue). During the long interval (wet or dry) solute concentration rises linearly according to its appearance or generation rate (minus any residual clearance by the kidneys or an ongoing wet day exchange). When APD cycles are initiated there is a concentration gradient for clearance and solute concentration falls. Dialysis and clearance is briefly arrested during the drain-refill phases of the cycle and then reestablished during the dwell phases so the urea concentration falls in steps. This is much more like hemodialysis and, ignoring the stepwise fall in solute concentration, we could derive a measure of the efficacy of solute removal by applying a measure using the predialysis and post dialysis solute concentration such as URR or Kt/V. Since solute concentration equilibrium is not reached during each APD cycle we cannot calculate dialysis dose efficacy purely based on the drainage volume.
N on-medical factor s and choice of APD
Daytime free of exchanges Dialysis time and exchanges overnight during sleep Reduced connecting (exchange) time Easier for care-helper
Urea concentration mg/dL
CDPB112013
94
Increasingly the reported reason for patients and physicians to prescribe APD versus CAPD is nonmedical. Compared to CAPD APD has the advantage that the daytime is more or less free of the need to perform bag exchanges (one daytime exchange is required for PD.plus prescription but can be incorporated into the cycler programming). The vast majority of patients perform APD overnight while asleep so that dialysis time does not conflict with the use of time for work, domestic or social activities. Assuming four exchanges per day and attention to proper technique and even with modern CAPD double-bag system, the time required to complete a bag exchange approximates one hour minimum. Thus at least 4 of 24 hours are consumed from the patients day simply performing the procedures and this time is consumed during the hours that a patient is likely to wish to undertake other activities. By contrast, a trained patient can set-up and disassemble a cycler before and after use in a time of 60 to 90 minutes. All of these considerations apply with even more relevance where the PD treatment is performed not by the patient but by a helper. This is the case for many children where the PD procedures are performed by a parent or sibling. Cyclers
Hospital use to home use

1964 1965 1966
1980s +
The main modality of peritoneal dialysis through the 1960s and into the 1970s was hospital-based IPD and not home-based therapy. This is reflected in the types of APD devices that were developed and used through this period as exampled in the upper panel above. When CAPD was established as a home-based, self-care modality it became apparent that there would be a need or desire for patients to be able to perform cycler assisted PD at home and the devices were modified to meet this need as suggested by the samples shown in the lower panel above.
CDPB112013
95
Basics of a PD cy cler
Fresh PD Fluid
Tubing giving systems Heater
Control System
Drained PD Fluid
The requirements of any PD cycler are the same. A source of fresh, sterile PD fluid usually provided in plastic bags. Since the volume of fluid required for a complete APD exchange (CCPD or NIPD) might be as high as 20 liters the bags are usually of 5L or 6L capacity and the cycler will require attachment via a tubing system of several (3 or 4) bags. The fresh PD fluid requires warming to near body temperature before instilling into the peritoneal cavity. The heater may be a flow through heater block (e.g., the sleep.safe) or a batch warmer such as an additional bag resting on a heating block. The centre of the cycler is the control system. What needs controlling is the direction of flow (fill or drain) and the volume of flow and the timing of alternation between fill, dwell and drain cycles. The driving force for flow may be gravity or pump-assisted. Where pumps are used a displacement diaphragm pump is preferred to a roller-pump. The control system is also required to determine the volume of the fill cycle and to be able to measure the volume of the drain cycle so that net flow of fluid (ultrafiltration) can be determined and read from the system. The direction of flow fresh fluid to peritoneal cavity during fill and spent fluid from peritoneal cavity to drain collection is controlled by valves (and pumps if present). Timers control the phases of the cycles. The various tubing systems, pump cassettes etc. are determined by the design of the cycler and will usually be provided as a disposables set.
CDPB112013
96
APD Cy cler s Ov er v iew

Low Cost Cyclers? New Platform?
The Future? 2002 1999-2000 1999 1994-95 1994-95
Development of machines need to be seen in the context of markets served While earlier development focused (relatively more) on the medical side of APD prescription, increasingly the future of APD is being linked for non-medical reasons such as cost of treatment and patient life-style
PD Adequacy As we saw for HD, we know that there is a relationship between outcomes such as survival and the dose of dialysis as solute removed. We discussed then the basis of Kt/V (for urea). We can say the same about PD modalities below a certain dose of solute removal mortality and other adverse outcomes rise suggesting a minimum dose of small solute removal below which therapy is clearly inadequate. Just as with HD we have problems when it comes to setting the ideal or optimum dose above what delivered dose is there no further benefit in terms of patient outcomes? In their original description of CAPD-equilibrium dialysis Moncrief and Popovich based their prescription on a model of urea kinetics in a well nourished 70 kg anuric man and arrived at 10 liter of PD fluid drained per day. This translated to a prescription of 8 to 10 liter of infused PD fluid per day and this became the standard CAPD prescription. In the early days few bothered to do more and little was done to individualize prescription or even to monitor delivered PD other than by measurement of blood values for solutes such as urea, creatinine, phosphates etc.
CAN USA 1996: fir st analy sis

Dose of dialysis (PD) is associated with risk of death
Probability of survival at 2 years (%)
2.3 80 95 2.1 1.9 1.7 1.5 60 80 70 55 40
100
RR of death reduced by 6% for weekly Kt/V(urea) 0.1
40
20
RR of death reduced by 7% for weekly CCr of 5 litre / 1.73m2
Kt/ V
CCr (L/week/1.73 m2 -
CANUSA / Churchill et al. JASN 1996 7: 198-207
As we have established in previous discussions, the required functions of dialysis include removal of retained solutes, electrolyte and acid-base balance and removal of retained salt and water to establish control of body fluid volume and hypertension. Fresenius Medical Care Asia Pacific
CDPB112013
97
As with hemodialysis, the prescription and monitoring of solute removal by PD focuses on small solutes urea and creatinine. Other aspects of solute management are simply monitored by interval measurements of blood concentrations of phosphates, calcium, electrolytes and serum bicarbonate or total carbon dioxide.
CAN USA based Guidelines: K/DOQI Ver sion 1

Weekly Dose of PD
Guideline 15 (Ev.):
For CAPD, the delivered PD dose should be a total Kt/Vurea of at least 2.0 per week and a total creatinine clearance (Ccr) of at least 60 l/wk/1.73m2.
Guideline 16 (Op.):
For NIPD, the weekly delivered PD dose should be a total Kt/Vurea of at least 2.2 and a total weekly creatinine clearance (Ccr) of at least 66 l/1.73m2. For CCPD, the weekly delivered PD dose should be a total Kt/Vurea of at least 2.1 and a total weekly creatinine clearance (Ccr) of at least 63 l/1.73m2.
The CANUSA findings had a major impact on the development of practice guidelines which were increasing in popularity in the late 1990s. The first version of the DOQI (USA) guideline for PD included the above guidance for dose and were based strongly on the CANUSA findings. The delivered dose of CAPD should be a total weekly Kt/V of 2 and weekly total creatinine clearance 60 liter. The doses for APD should be higher because these therapies were not continuous and therefore clearance measurements underestimated real whole body effects.
CAN USA - Residual renal function

100 2.5 2.0
2.38
80
83.0
Ccr (l/1.73 m 2)
Kt/V
1.5 1.0 0.5 0.0
1.67
60 40 20
44.2 44.6 46.4 45.3 47.3
1.67 1.68 1.66 1.70
38.8
0.71 0
0.58 6
30.1
0.41 12 Months
0.39 18
0.28 24
21.9 12
20.4 18
14.3 24
0 0 6
months renal peritoneal
Months months
In HD there has been little interest in residual renal function probably because traditionally it was known that renal function rapidly deteriorated after starting HD. Such is not the case in PD. The data shown here from the CANUSA study indicate the change in the contribution of residual renal function to solute clearances over a two-year time frame. Over two years there is a progressive decline in total clearances which is entirely explained by the loss of the contribution of residual renal function which is partially, but incompletely compensated by slight increase in the peritoneal contribution to clearance. Fresenius Medical Care Asia Pacific
CDPB112013
98
At the commencement of therapy with PD, clearances are more than adequate but barely reach adequacy targets after only two years. When renal function contributes more than about 0.3 weekly Kt/V(urea) or more than 20 liter creatinine clearance / 1.73m2 per week, the targets described by DOQI can be achieved for a majority of patients. As renal function declines over time targets are more difficult to achieve and even impossible to achieve by standard CAPD in large patients.
Pr escr ibing ultr afiltr ation

E mpirical method
Prescribe assess represcribe ( trial and error )
M odeling
Perform one or other test of peritoneal permeability (PE T, PFT etc.) Insert relevant data into model (e.g., 3-pore model) Read prescription alternatives Assess achieved UF against modeled-predicted
In reality two approaches are used to prescribe the ultrafiltration required by the PD patient. The first (and still the most common) is trial and error. Depending upon known patient characteristics including residual urine volume, cardiovascular and hypertension status, a PD regimen (CAPD or APD) is prescribed as a first prescription. The patient and clinician then monitor relevant outcomes including PD exchange volumes and dextrose concentration, PD total effluent, daily weight etc. and empirically determine whether the prescription satisfies the patients needs. Changes in PD prescription number of exchanges, dextrose concentration, icodextrin exchange, APD versus CAPD are made based on the empirical findings. The alternative and probably better approach is to assess peritoneal solute permeability using a test such as the PET or PFT and to insert data derived from the results into a model which then predicts the UF response to different dextrose concentrations and dwell duration. Such models are available on various software systems . The models that are most commonly applied use and assume that the 3-pore model described in an earlier module is valid. The model outputs include CAPD and APD regimens, exchange volumes, duration and dextrose concentration of the exchanges which can be built into a PD regimen. We will examine such outputs in the next module. The prescription is then applied and monitored at some subsequent time.
CDPB112013
99
PD Prescription and Nutrition

Food and energy requirements in PD patients
Energy requirement: Energy substances Proteins Fats Carbohydrates recommended intake 1.2 g/kg/day Max. 30% of energy 35 kcal/kg/day Energy content 1 g ~ 4 kcal 1 g ~ 9 kcal 1 g ~ 4 kcal per day for a 70 kg man 84 g ~ 336 kcal 82 g ~ 735 kcal 345 g ~ 1379 kcal
345 200 180 160 140
Food intake per day for a 70 kg adult

84 82 Carbohydrates 55-60%
Proteins 10-15%
grams (g)
120 100 80 60 40 20 0
Fats max. 30%
% of energy requirement
Proteins
Fats
Carbohydrates
A summary of the recommended distribution of dietary food types and their contribution to calorie intake for PD patients is shown here. The needs of a 70 kg patient simply to serve the metabolic and heat generation exceed 1,800 kCal per day: modest physical activities of daily living require additional calories and at 35 kCal per day the patient requires ~ 2,450 kCal per day. More calories would be needed for any activity beyond routine daily activities e.g., a modest daily exercise regimen. Fats are the most weight-effective means of delivering calories (9 kCal per gram) but accepted guidelines indicate that fat intake should not exceed 30% of total calorie intake. The recommendations are that the calorie intake attributable to carbohydrate intake should be between 55% and 60% of total. (Note: the recommendation is similar for diabetic patients).
Summary
Prescription of PD regimens addresses issues of solute removal adequacy and volume management by ultrafiltration CAPD prescription and monitoring is relatively easy by manual means APD prescription requires use of mathematical models of peritoneal function and computer softw are Nutritional requirements and metabolic issues need to be considered in PD prescriptions
CDPB112013
For exclusive use of Lualhati, Anna Lourdes 100
NOTES ............................................................................................................................................................ ....................................................................................................................................................................... ....................................................................................................................................................................... ....................................................................................................................................................................... ....................................................................................................................................................................... ............................................................................................................................................................ ....................................................................................................................................................................... ....................................................................................................................................................................... ....................................................................................................................................................................... ....................................................................................................................................................................... ....................................................................................................................................................................... ............................................................................................................................................................ ....................................................................................................................................................................... . Activity: Describe the following concepts on Peritoneal Dialysis. o CAPD _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________________________ ____________________________________________________________ o APD _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________ o NIPD _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________ o PD Plus _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________ o Exchanges in PD _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________________________ _________________________________________________________ o Peritonitis _________________________________________________________________________ _________________________________________________________________________ Fresenius Medical Care Asia Pacific
CDPB112013
_________________________________________________________________________ _________________________________________________________
CONTINOUS QUALITY IMPROVEMENT & CLINICAL PRACTICE IMPROVEMENT
The basic principles of CQI were presented (Axley,2008), including the philosophy that guides the CQI process today in many industries, including health care. Known as the Father of Modern CQI, Dr. W. Edward Demings philosophy includes viewing problems as opportunities, improving processes or systems instead of blaming individuals, and advocating for decision-making based on facts and data (Walton, 1986). The CQI process was defined as addressing 4 basic questions: Where are we now? Why do we want to change where we are? Where do we want to go? How are we going to get there? CQI is an active process in which a need for improvement is identified and appropriate members of a team who are affected by or involved in the problem under consideration are selected. The team collects and analyzes baseline data so they can define where they are and why they want to change. Finally, based on their data and its analysis, they determine one or two root causes of the problem that they think can be improved upon. This allows the team to start looking ahead at where they want to go and how they want to get there (Axley, 2008).
CQI PDCA CYCLE Plan - Steps 1 - IV Do - Step V Check - Step VI Act - Step VII
CDPB112013
This process can be conducted using the Plan, Do, Check, and Act (PDCA) cycle (see Figure 1). PDCA is a simplification of the scientific method that was made popular by Deming (1986). The steps included in the PDCA cycle are: P Plan the action steps. Study a particular process to determine what changes might be desirable. Organize a team and collect data to better define the problem. Decide how you will use your observations and data related to the need for that improvement. Develop a plan for an improvement. D Do the action steps you have defined. Implement the change process you have described in your plan. C Check the outcomes. Monitor and evaluate the processes and results of your change. What were the effects? What did you learn? Did the outcomes match the desired elements you had established? A Act based on the results. Were you successful in accomplishing the desired change? Were the results different from what you expected? Review the outcomes of the PDCA cycle and modify the improvement process based on the knowledge that you have gained. Return to the Plan phase and repeat the cycle until the goals, original or modified, have been achieved (Deming, 1994).
Clinical Indicators + HRQoL= OUTCOMES
Clinical Indicators
Establish Targets -CPG Act Quality of Life Patient Feedback Plan changes Identify Outliers
Qualitative data Quantitative data
2
Monitor
CDPB112013
Dialysis Targets ; DOQI, CARI, BRA,CSN

HD dose 1.3 spKt/V (URR 65%) 1.4 spKt/V weekly Kt/V = 4.2 HCO23-24mmol/L (20-24mmol/L) Calcium 2.2-2.6 mmol/L (2.45 mM/L)
Calcium< 9.8 mg/dL
PD Dose Kt/Vw > 2
Anaemia 11-12 g/dL (33-36% Hct)
Access Fistula > 80% (R-C AVF) BBT- AVF AVG
BP
<140/90 <160/90
Nutrition > 40g/L SGA nPNA >1.2 >1.3
(diabetic & PD )
CaXPO4 < 5.8 mM2/L2 < 2.9 iCa++

< 55 mg2/L2
(<4.2 or 2.6 iCa)
Phosphate < 2.2 mmol/L <1.8 mmol/L (< 5.5 mg/dL)
T echniq ues f or a na ly zing a q ua lity p r ocess
1 . 2 . 3 . 4 . 5 .
Flow Cha r ts Fish-b one (Ca use & effect) Histogr a ms Fr eq uency cha r ts Id entification of Outlier s
The CQI process can be used in nephrology nursing to address regulatory compliance issues as well as clinical opportunities for improvement. As reported by Levy (2008), regulatory agencies, including the Joint Commission for the Accreditation of Healthcare Organizations (The Joint Commission) and Centers for Medicare and Medicaid (CMS), welcome the inclusion of the CQI process in addressing areas for improvement in facilities. Reporting of water quality, blood stream infections (BSI), occurrence reports, equipment preventive maintenance and repairs, as well as medication errors are frequently addressed in this manner. Clinical parameters, such as hypotensive episodes, adequacy of dialysis, achieving prescribed fluid removal, access issues, and delays in initiating treatment, also lend themselves well to the CQI process.
CDPB112013
Data Collection Management What data is required? o Level of data o Relationship to type of analysis Where do you get the data from? o Data base o Patients/clients o Health authorities Validity and reliability of data? o Relationship to problem/question o Data collection technique o Input (data base entry) & analysis
Descriptive Statistics
Tabular
Nominal Frequency tables (discrete categories)
Graphical
Bar graphs Pie graphs
Location
Mode
Spread
Ordinal
Frequency tables (Ordered categories)
Bar graphs Pie graphs
Median
Equal Interval
Frequency tables (continuous categories)
Histograms Frequency polygons
Mean Median Mode
Range Variance Standard deviation
Sources of Data Medline (Pubmed) CINAHL Health Agencies

CDPB112013
Thesis works (library) Support groups Ministry of Health Government Agencies Own Clinical Environment
Validity and Reliability of Data Reliability the instrument does so in a range of settings and with different researches. Internal Validity independent and dependent variables. External Validity - the degree to which the result of an experiment may be extended to other samples of the same population and to other populations.. Errors in Data Collection - Instrument inadequacies; refers to the reliability and validity of instrument.. - Instrument biases with instrument. This is more common when > 1 researcher Environmental factors; data collection maybe influenced by differences in environment. Characteristics of the subject; ie, pain, anxiety, tiredness may influence results.
Data Organization Organizing Data o To answer research question/hypothesis o Categorizing the variables o Data spreadsheet Decimal points Coding Accuracy Cleaning Data o Sorting data
CDPB112013
Data Analysis Descriptive Analysis o Describes the data o Central tendency Mean Average - Measure of central tendencies - Should always be presented with standard deviation - Common statistics used - Continuous data Mode - Most frequent point - Peak of curve Median - 50% point of scores - Used for median survival score Frequency - Count for different scores/categories Dispersion statistics Standard deviation most common statistics of dispersion, - used in conjunction with the mean, - presents the deviation away from the mean, - represents the shape of the curve. Variance
CDPB112013
Characteristics in Health Care ; E SRD Population

Age Gender Renal Aetiology Mode of dialy sis Time on dialy sis Kt/V; Nutritional & Haemoglobin parameters Rehabilitation status
Presentation of Data Describe the data Visual presentation - Tables - Graphs Statistics tables Tables and Graphs - Clear - Not misleading regarding the effect of the statistics - Use appropriate graphs & statistics for level of data - Present the significance level with the statistics
Kt/V Histogram
25 20
Visual Presentation of Data

90 80 70 60 50 40 30 20 10 0 1st Qtr 2nd Qtr 3rd Qtr 4th Qtr
Frequency
15 10 5 0
95
28
61
94
5 2. 10
1.
1.
Diabetic
vs Non diabetic
1.
M or
1 2
11
44
0.
1.
1.
77
Table
The role of Albumin
Pie chart
F.I.D.N._R082011
1.
CDPB112013
Data Management Activity

1. Present the descriptive statistics for Kt/V; diabetic vs non-diabetic Hb
EPO dosage Iron (TS%) FOR Hb < 10 gm/dl
nPNA
Albumin level for those with nPNA < 1.0
Phosphate
Albumin level for those with phosphate < 4.0
Calcium Phosphate product
The role of Albumin
F.I.D.N._R082011
NEPHROLOGY NURSING JOURNAL September-October 2008 Vol. 35, No. 5
Data Management Activity

2. Graph the parameters Kt/V
diabetic non-diabetic
Hb
EPO dosage for all & those < 10 gm/dl Iron (TS%) FOR Hb < 10 gm/dl
nPNA Phosphate
The role of Albumin
F.I.D.N._R082011
Activity: With the following data provided, make a graphical presentation, analysis and plan of action for set/s of patient population. Discuss this is class. REFERENCE SOURCES Fresenius Medical Care Asia Pacific
CDPB112013
Water water (20% (30 -
llular al lular (L) ody

1. USRDS Annual Report (2008) International Comparisons, www.usrds.org 2. Kjellstrand, CM. (2001) Rationale for daily hemodialysis. ASAIO Journal, 47(5), 438-442. 3. Lindsay, R and Kortas, C. (2001) Hemeral (Daily) hemodialysis. Advances in Renal Replacement Therapy. 8 (4) 236-249. 4. KDOQI Guidelines http://www.kidney.org/professionals/kdoqi/guidelines.cf 5. CARI Guidelines http://www.cari.org.au/guidelines.php 6. Kronner, K, Nonnast-Daniel B and Ritz, E 2003. (2003) The Arteriovenous fistula. Journal Am Soc Nephrol 14: 1669-1680. 7. Daugirdaus and Ing. The Handbook of Dialysis 8. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004; 351:12961305. 9. Grooteman MP, Nube MJ, Daha MR, et al. Cytokine profiles during clinical high-flux dialysis: no evidence for cytokine generation by circulating monocytes. J Am Soc Nephrol. 1997; 8:1745 1754. 10. Sitter T, Bergner A, Schiffl H. Dialysate related cytokine induction and response to recombinant human erythropoietin in hemodialysis patients. Nephrol Dial Transplant. 2000; 15:12071211. 11. Schindler R, ChristKohlrausch F. et al. Differences in the permeability of high-flux dialyzer membranes for bacterial pyrogens. Clin Nephrol. 2003; 59:447454.
12. Merello Godino JI, Rentero R, Orlandini G, et al. Results from EuCliD (European Clinical Dialysis Database): impact of shifting treatment modality. Int J Artif Organs. 2002; 25:10491060. 13. Oberg BP. Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int. 2004; 65:10091016. 14. Galle J, Seibold S, Wanner C. Inflammation in uremic patients: what is the link? Kidney Blood Press Res. 2003; 26:6575. 15. Canaud B, Morena M, Leray-Moragues H, et al. Overview of clinical studies in hemodiafiltration: what do we need now? Hemodial Int. 2006; 10 (Suppl. 1):S5S12. 16. Altieri P, Sorba GB, Bolasco PG, et al. On-line predilution hemofiltration versus ultrapure highflux hemodialysis: a multicenter prospective study in 23 patients. Sardinian Collaborative Study Group of On-Line Hemofiltration. Blood Purif. 1997; 15:169181. 17. Tenckhoff H, Schechte H. A bacteriological safe peritoneal access device. Trans Am Soc Artif Intern Organs 14:181-186, 1968 18. Nephrology Nursing Journal September-October 2008 Vol. 35, No. 5
CDPB112013

CDP B - Lualhati, Anna Lourdes (1) - NoRestriction

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

CDP B - Lualhati, Anna Lourdes (1) - NoRestriction

Uploaded by

Copyright:

Available Formats

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

www.dopps.org www.hdcn.org www.isn-online.org

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Vascular Space (5 Litres)

Interstitial Space (10 Litres)

Intracellular Space (25 Litres)

Cell membrane interface

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

C. ACID BASE BALANCE

TCO2 Potassium Sodium

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

nPNA Albumin TCO2 Pre Urea Phosphate

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Peripheral Neuropathy Paresthesias Motor weakness

For exclusive use of Lualhati, Anna Lourdes

KDOQI NKF STRATEGY FOR STAGING CKD

Tertiary Prevention: reducing the complications

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Nitric oxide Cytokines Growth Factors

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Modality of renal replacement therapy

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Classification of Uremic Toxins

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific

For exclusive use of Lualhati, Anna Lourdes

Fresenius Medical Care Asia Pacific