Chronic Kidney

Disease
NEPHROLOGY ROUNDS

Jose Socrates Dee Matuod Evardone

Year Level 2
Nephrology 2

PRE TEST

PRETEST

1) Urine albumin per gram of creatinine

content that signifies Chronic Renal
Damage:
A.17mg in males, 25mg in females
B.25mg in males, 17mg in females
C. 25mg in both sexes
D. None of the above

PRETEST

2) In CKD with Uremia, these compounds

with a molecular mass between 500 and
1500 Da, are also retained and contribute to
morbidity and mortality
A. Guanidino compounds
B. products of nucleic acid metabolism
C. Polyamines
D.middle molecules

PRETEST

3) Diuretics used in combination of loop

diuretics, which inhibits the sodium
chloride co-transporter in the distal
convoluted tubule, can help effect renal
salt excretion:
A. Ethacrynic acid
B.Metolazone
C. Acetazolamide
D. Eplerenone

PRETEST

4) The combination of ACE inhibitor and

ARB is associated with a greater

reduction in proteinuria compared to
either agent alone.

True or False

PRETEST

5) Testing for microalbumin is

recommended in all diabetic patients at

least:
A. Every
B. Every
C. Every
D. Every

6 months
3 months
12 months
clinic visit

PRETEST

6) CKD is defined by the presence of

kidney damage or decreased kidney
function, irrespective of the cause, for
at least:
A.2 months
B.3 months
C.6 months
D. 12 months

PRETEST

7) In CKD dietary recommendation, at least

how much of the protein intake should be of
high biologic value:
A. 50%
B. 40%
C. 60%
D. 30%

PRETEST

8) In CKD, NO dose adjustment is needed for

agents/drugs that are excreted by a nonrenal
route by more than:
A. 50%
B. 60%
C. 70%
D. 80%

PRETEST

9) In CKD, educational programs should be

commenced no later than stage __ CKD so that the
patient has sufficient time and cognitive
function to learn the important concepts, to make
informed choices, and implement preparatory
measures for renal replacement therapy.

A. Stage 2
B. Stage 3
C. Stage 4
D. Stage 5

PRETEST

10) Parathyroid hormone(PTH) itself is

considered a uremic toxin.

True or False

Topic Outline
I INTRODUCTION
II CLINICAL AND LABORATORY MANIFESTATIONS OF
CHRONIC KIDNEY DISEASE AND UREMIA
III EVALUATION AND MANAGEMENT OF PATIENTS
WITH CKD
IV TREATMENT

Topic Outline
I

INTRODUCTION

A. PATHOPHYSIOLOGY OF CHRONIC KIDNEY

DISEASE
B. IDENTIFICATION OF RISK FACTORS AND
STAGING OF CKD
C. ETIOLOGY AND EPIDEMIOLOGY
D.PATHOPHYSIOLOGY AND BIOCHEMISTRY OF
UREMIA

Topic Outline
II

CLINICAL AND LABORATORY MANIFESTATIONS OF

CHRONIC KIDNEY DISEASE AND UREMIA
A. FLUID, ELECTROLYTE, AND ACID-BASE DISORDERS
1. Sodium and water homeostasis
2. Potassium homeostasis
3. Metabolic acidosis

B. DISORDERS OF CALCIUM AND PHOSPHATE METABOLISM

1. Bone manifestations of CKD
2. Calcium, phosphorus, and the cardiovascular system
3. Other complications of abnormal mineral metabolism

C.

CARDIOVASCULAR ABNORMALITIES
1. Ischemic vascular disease
2. Heart failure
3. Hypertension and left ventricular hypertrophy
4. Pericardial disease

Topic Outline
II CLINICAL AND LABORATORY
MANIFESTATIONS OF CHRONIC KIDNEY DISEASE
AND UREMIA
D. HEMATOLOGIC ABNORMALITIES
1. Anemia
2. Abnormal hemostasis

E. NEUROMUSCULAR ABNORMALITIES
F. GASTROINTESTINAL AND NUTRITIONAL
ABNORMALITIES
G. ENDOCRINE-METABOLIC DISTURBANCES
H. DERMATOLOGIC ABNORMALITIES

Topic Outline
III

EVALUATION AND MANAGEMENT OF

PATIENTS WITH CKD
A.INITIAL APPROACH
1.History and physical examination
2.Laboratory investigation
3.Imaging studies
4.Renal biopsy
B.ESTABLISHING THE DIAGNOSIS AND
ETIOLOGY OF CKD

Topic Outline
IV

TREATMENT

A.SLOWING THE PROGRESSION OF CKD

1.Reducing Intraglomerular Hypertension and Proteinuria
B.SLOWING PROGRESSION OF DIABETIC RENAL DISEASE
1.Control of Blood Glucose
2.Control of Blood Pressure and Proteinuria
3.Protein Restriction
C.MANAGING OTHER COMPLICATIONS OF CHRONIC KIDNEY
DISEASE
1.Medication Dose Adjustment
2.Preparation for Renal Replacement Therapy
3.Patient Education

CASE
E.R.
63M
HTN>10yrs, poor med compliance
nonDM
previously smoker(stopped 15ys ago)
alcoholic beverage drinker(2beer/week)
CC: DYSPNEA

CASE
HPI:
1 month ago: exertional dyspnea
plus, 2 pillow orthopnea, loss of appetite,
body malaise, nausea and vomiting
admitted at CVGH, creatinine was 20mg/dl,
px was advised for hemodialysis (did not
consent)

CASE
HPI:
1 week PTA:
Bilateral LE swelling
weight loss
Oliguria
Dyspnea at rest

P.E.

Awake, in respiratory
distress

BP: 190/100mmHg
PR: 98 bpm
RR: 35 cpm
Temp: 36.2C
Anicteric sclerae, Pale
palpebral conjunctivae

SKIN: cold,clammy

C/L: Equal chest expansion,

bibasal rales, decrease
breath soundson the left
lower lobe

ABD: Normoactive bowel

sounds, soft, non tender, no
organomegaly

CVS: Distinct heart sounds,

normal rate, regular rhythm

EXT: Bipedal edema grade 3

NEURO: Unremarkable

ECG

LABS
CBC
Hgb
Hct
WBC
Seg
Bas
Eos
Lymph
Mono

Adm
5.4
16.8
11.3
95
0
0
2
3

RBC
Platelet
MCV
MCH
MCHC

2.56
121
65.6
21.1
32.2

RENAL PANEL C
ABG
pH
6.99
pCO2 17
pO2
300
HCO3 4.2
fiO2
60%
SO2
100%
pF
500
ratio
Temp 36.2

LABS

RENAL PANEL C
Glucose
BUN
Creatinine
Uric Acid
Calcium
Phosphoru
s
Sodium

107 mg/dl
197 mg/dl
37.8 mg/dl
8.7 mg/dl
5.6 mg/dl
17.6 mg/dl

127
mmol/L
Potassium 6.8 mmol/L
Chloride
89 mmol/L
Enz. CO2
8.0 mmol/L

Total Chole
Triglycerid
es
Total
Protein
Albumin
Globulin
A/G Ratio
SGPT/ALT
Allk Phos

99 mg/dl
103 mg/dl
5.4 g/dL
2.9 g/dL
2.5 g/dL
0.7
38 U/L
70 U/

IMPRESSION
1. ESRD with Uremia sec. to Hypertensive Nephrosclerosis
2. Pulmonary Congestion sec . to Fluid Overload sec. to #1
3. Metabolic acidosis, part. Compensated sec. to #1
4. Electrolyte Imbalance sec to #1
5. Essential Hypertension
6. CAP-High Risk
7. Microcytic, Hypochromic Anemia sec to #1

Abbreviations
NKF - National Kidney Foundation

KDOQI - Kidney Disease Outcomes Quality Initiative

KDIGO - Kidney Disease Improving Global Outcomes

What is CKD?
CKD is defined by the
presence of kidney damage or
decreased kidney function
for three or more months,
irrespective of the cause.

What is CKD?
The persistence of the damage or decreased
function for at least three months is necessary
to distinguish CKD from acute kidney disease.

Kidney damage refers to pathologic

abnormalities, whether established via:
1. renal biopsy or
2. imaging studies, or
3. inferred from markers such as
a) urinary sediment abnormalities or
b) increased rates of urinary albumin
excretion.

What is CKD?
Chronic kidney disease is defined based on
the presence of either kidney damage or
decreased kidney function for three or more
months, irrespective of cause.

Criteria:
Duration 3 months, based on documentation
or inference
Glomerular filtration rate (GFR) <60
mL/min/1.73 m2
Kidney damage, as defined by structural abnormalities
or functional abnormalities other than decreased GFR

CHRONIC KIDNEY DISEASE

Duration 3 months, based on

documentation or inference

Duration is necessary to distinguish chronic from acute

kidney diseases.
1. Clinical evaluation can often suggest duration
2. Documentation of duration is usually not
available in epidemiologic studies

CHRONIC KIDNEY DISEASE

Glomerular filtration rate (GFR) <60

mL/min/1.73 m2

GFR is the best overall index of kidney function in

health and disease.
1. The normal GFR in young adults is approximately
125 mL/min/1.73 m2; GFR <15 mL/min/1.73 m2
is defined as kidney failure
2. Decreased GFR can be detected by current
estimating equations for GFR based on serum
creatinine (estimated GFR) but not by serum
creatinine alone
3. Decreased estimated GFR can be confirmed by
measured GFR

CHRONIC KIDNEY DISEASE

Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

A)

Pathologic abnormalities (examples). Cause is based on

underlying illness and pathology. Markers of kidney damage
may reflect pathology.
1. Glomerular diseases (diabetes, autoimmune diseases,
systemic infections, drugs, neoplasia)
2. Vascular diseases (atherosclerosis, hypertension,
ischemia, vasculitis, thrombotic microangiopathy)
3. Tubulointerstitial diseases (urinary tract infections,
stones, obstruction, drug toxicity)
4. Cystic disease (polycystic kidney disease)

CHRONIC KIDNEY DISEASE

Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

B)

History of kidney transplantation. In addition to

pathologic abnormalities observed in native kidneys, common
pathologic abnormalities include the following:
1. Chronic allograft nephropathy (non-specific findings of
tubular atrophy, interstitial fibrosis, vascular and
glomerular sclerosis)
2. Rejection
3. Drug toxicity (calcineurin inhibitors)
4. BK virus nephropathy
5. Recurrent disease (glomerular disease, oxalosis, Fabry
disease)

CHRONIC KIDNEY DISEASE

Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

C)

Albuminuria as a marker of kidney damage (increased

glomerular permeability, urine albumin-to-creatinine ratio
[ACR] >30 mg/g).*
1. The normal urine ACR in young adults is <10 mg/g.
Urine ACR categories 10-29, 30-300 and >300 mg are
termed "high normal, high, and very high"
respectively. Urine ACR >2200 mg/g is accompanied by
signs and symptoms of nephrotic syndrome
2. Threshold value corresponds approximately to urine
dipstick values of trace or 1+
3. High urine ACR can be confirmed by urine albumin
excretion in a timed urine collection

CHRONIC KIDNEY DISEASE

Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

D) Urinary sediment abnormalities as markers of kidney

damage
1. RBC casts in proliferative glomerulonephritis
2. WBC casts in pyelonephritis or interstitial nephritis
3. Oval fat bodies or fatty casts in diseases with
proteinuria
4. Granular casts and renal tubular epithelial cells
in many parenchymal diseases (non-specific)

CHRONIC KIDNEY DISEASE

Kidney damage, as defined by structural abnormalities or functional
abnormalities other than decreased GFR

E)

Imaging abnormalities as markers of kidney damage

(ultrasound, computed tomography and magnetic resonance
imaging with or without contrast, isotope scans,
angiography).
1. Polycystic kidneys
2. Hydronephrosis due to obstruction
3. Cortical scarring due to infarcts, pyelonephritis or
vesicoureteral reflux
4. Renal masses or enlarged kidneys due to infiltrative
diseases
5. Renal artery stenosis
6. Small and echogenic kidneys (common in later stages
of CKD due to many parenchymal diseases)

PATHOPHYSIOLOGY OF
CHRONIC KIDNEY DISEASE
Two broad sets of mechanisms
of damage:
1. initiating mechanisms specific to the
underlying etiology
2. a set of progressive mechanisms
- hyperfiltration and hypertrophy of the
remaining viable nephrons

PATHOPHYSIOLOGY OF
CHRONIC KIDNEY DISEASE
Two broad sets of mechanisms
of damage:
1. initiating mechanisms specific to the
underlying etiology
2. a set of progressive mechanisms
- hyperfiltration and hypertrophy of the
remaining viable nephrons

PATHOPHYSIOLOGY OF
CHRONIC KIDNEY DISEASE
Increased intrarenal activity of the
renin-angiotensin axis appears to
contribute both to:
initial adaptive hyperfiltration
the subsequent maladaptive hypertrophy
and sclerosis (TGF-)

Left: Schema of the normal glomerular

architecture.
Right: Secondary glomerular changes

IDENTIFICATION OF RISK FACTORS AND

STAGING OF CKD

Risk factors:
1.
2.
3.
4.
5.
6.
7.
8.

hypertension,
diabetes mellitus,
autoimmune disease,
older age,
African ancestry,
a family history of renal disease,
a previous episode of acute kidney injury,
and the presence of
a. proteinuria,
b. abnormal urinary sediment, or
c. structural abnormalities of the urinary tract

Recommended Equations for Estimation of

Glomerular Filtration Rate (GFR) Using
Serum Creatinine Concentration (PCr), Age, Sex,
Race, and Body Weight
1) Equation from the Modification of Diet in
Renal Disease study (MDRD)

2) Cockcroft-Gault equation

CKD

IDENTIFICATION OF RISK FACTORS AND

STAGING OF CKD

Chronic renal damage

Persistence in the urine of:
>17 mg of albumin per gram of
creatinine in adult males and
25 mg albumin per gram of creatinine in
adult females

ETIOLOGY AND EPIDEMIOLOGY

Leading Categories of Etiologies
of CKD
Diabetic glomerular disease
Glomerulonephritis
Hypertensive nephropathy
Primary glomerulopathy with
hypertension
Vascular and ischemic renal disease
Autosomal dominant polycystic kidney
disease
Other cystic and tubulointerstitial
nephropathy

ETIOLOGY AND EPIDEMIOLOGY

Newly diagnosed CKD:
present with hypertension
CKD is often attributed to hypertension:
When no overt evidence for a primary
glomerular or tubulointerstitial kidney disease
process is present

ETIOLOGY AND EPIDEMIOLOGY

Two Categories:
1) patients with a silent primary
glomerulopathy
2) patients in whom progressive
nephrosclerosis and
hypertension is the renal correlate
of a systemic vascular disease

Multiple Functions of the Kidneys

1) Excretion of metabolic waste
products and foreign chemicals
2) Regulation of water and
electrolyte balances
3) Regulation of body fluid
osmolality and electrolyte
concentrations
4) Regulation of arterial pressure
5) Regulation of acid-base balance
6) Secretion, metabolism, and
excretion of hormones
7) Gluconeogenesis

PATHOPHYSIOLOGY AND BIOCHEMISTRY

OF UREMIA
Elevated waste products:
Hundreds of toxins, water-soluble,
hydrophobic, protein- bound, charged, and
uncharged compounds, guanidino
compounds, urates and hippurates, products of
nucleic acid metabolism, polyamines,
myoinositol, phenols, benzoates,
and indoles
middle molecules

PATHOPHYSIOLOGY AND BIOCHEMISTRY

OF UREMIA
A host of metabolic and endocrine
functions normally performed by the
kidneys is also impaired or
suppressed:

anemia,

malnutrition,

and abnormal metabolism of

carbohydrates, fats, and proteins

PATHOPHYSIOLOGY AND BIOCHEMISTRY

OF UREMIA
Urinary retention, decreased
degradation, or abnormal regulation
of hormones
PTH,
FGF-23,
insulin,
glucagon,
steroid hormones including vitamin D
and sex hormones, and
prolactin

3 Spheres of dysfunction of Uremic

Syndrome

Toxins

URE
M

Progressive
systemic
inflammation

Homeostasis

CLINICAL AND LABORATORY

MANIFESTATIONS OF
CHRONIC KIDNEY DISEASE
AND UREMIA

CLINICAL ABNORMALITIES IN UREMIA

1. Fluid and electrolyte disturbances
2. Endocrine-metabolic disturbances
3. Neuromuscular disturbances
4. Cardiovascular and pulmonary
disturbances
5. Dermatologic disturbances
6. Gastrointestinal disturbances
7. Hematologic and immunologic disturbances
(I) improves with an optimal program of dialysis and
related therapy;
(P) persist or even progress, despite an optimal
program; (D) develops only after initiation of dialysis
therapy.

CLINICAL ABNORMALITIES IN UREMIA

1. Fluid and electrolyte disturbances
a. Volume expansion (I)
b. Hyponatremia (I)
c. Hyperkalemia (I)
d. Hyperphosphatemia (I)

(I) improves with an optimal program of dialysis and related

therapy;
(P) persist or even progress, despite an optimal program;
(D) develops only after initiation of dialysis therapy.

CLINICAL ABNORMALITIES IN UREMIA

2. Endocrine-metabolic disturbances
1. Secondary hyperparathyroidism (I or P)
2.Adynamic bone (D)
3. Vitamin Ddeficient osteomalacia (I)
4. Carbohydrate resistance (I)
5. Hyperuricemia (I or P)
6. Hypertriglyceridemia (I or P)
7. Increased Lp(a) level (P)
8. Decreased high-density lipoprotein level (P)
9. Protein-energy malnutrition (I or P)
10.Impaired growth and development (P)
11.Infertility and sexual dysfunction
(P)
(I) improves with an optimal program of dialysis and
related therapy;
12.Amenorrhea (I/P)
(P) persist or even progress, despite an optimal
13.2-Microglobulinassociated
amyloidosis (P or D)
program;
(D) develops only after initiation of dialysis therapy.

CLINICAL ABNORMALITIES IN UREMIA

3. Neuromuscular disturbances
1.Fatigue (I)b
2.Sleep disorders (P)
3.Headache (P)
4.Impaired mentation (I)b
5.Lethargy (I)b
6.Asterixis (I)
7.Muscular irritability
8.Peripheral neuropathy (I or P)
9.Restless legs syndrome (I or P)
10.Myoclonus (I)
(I) improves with an optimal program of dialysis and
11.Seizures (I or P)
related therapy;
(P) persist or even progress, despite an optimal
12.Coma (I)
program;

CLINICAL ABNORMALITIES IN UREMIA

4. Cardiovascular and pulmonary disturbances
1.Arterial hypertension (I or P)
2.Congestive heart failure or pulmonary edema (I)
3.Pericarditis (I)
4.Hypertrophic or dilated cardiomyopathy (I, P, or D)
5.Uremic lung (I)
6.Accelerated atherosclerosis (P or D)
7.Hypotension and arrhythmias (D)
8.Vascular calcification (P or D)
(I) improves with an optimal program of dialysis and
related therapy;
(P) persist or even progress, despite an optimal
program;
(D) develops only after initiation of dialysis therapy.

CLINICAL ABNORMALITIES IN UREMIA

5. Dermatologic disturbances
1.Pallor (I)b
2.Hyperpigmentation (I, P, or D)
3.Pruritus (P)
4.Ecchymoses (I)
5.Nephrogenic fibrosing dermopathy (D)
6.Uremic frost (I)
(I) improves with an optimal program of dialysis and
related therapy;
(P) persist or even progress, despite an optimal
program;
(D) develops only after initiation of dialysis therapy.

CLINICAL ABNORMALITIES IN UREMIA

6. Gastrointestinal disturbances
1.Anorexia (I)
2.Nausea and vomiting (I)
3.Gastroenteritis (I)
4.Peptic ulcer (I or P)
5.Gastrointestinal bleeding (I, P, or D)
6.Idiopathic ascites (D)
7.Peritonitis (D)
(I) improves with an optimal program of dialysis and
related therapy;
(P) persist or even progress, despite an optimal
program;
(D) develops only after initiation of dialysis therapy.

CLINICAL ABNORMALITIES IN UREMIA

7. Hematologic and immunologic disturbances

1.Anemia (I)b
2.Lymphocytopenia (P)
3.Bleeding diathesis (I or D)b
4.Increased susceptibility to infection
5.(I or P)
6.Leukopenia (D)
7.Thrombocytopenia (D)

(I) improves with an optimal program of dialysis and

related therapy;
(P) persist or even progress, despite an optimal
program;
(D) develops only after initiation of dialysis therapy.

FLUID, ELECTROLYTE, AND ACID-BASE

DISORDERS

S
O
DI
U
M

FLUID, ELECTROLYTE, AND ACID-BASE

DISORDERS
Hyponatremia water restriction
ECFV expansion salt restriction
S
O
D
I
U
M

Thiazides limited utility in stages 3-5 CKD

- loop diuretics needed

Loop Diuretics resistance Higher doses

Metolazone combined with loop diuretics, which
inhibits the sodium chloride co-transporter of the distal
convoluted tubule, can help effect renal salt excretion

FLUID, ELECTROLYTE, AND ACID-BASE

DISORDERS

HYPERKALEMIA
P
O
T
A
S
SI
U
M

Precipitated by
increased dietary potassium intake,
protein catabolism,
hemolysis,
hemorrhage,
transfusion of stored red blood cells,
and metabolic acidosis
Medications

Renal Potassium
Handling

FLUID, ELECTROLYTE, AND ACID-BASE

DISORDERS
Hypokalemia:
P
O
T
A
S
SI
U
M

Not common in CKD

reduced dietary potassium intake
GI losses
Diuretic therapy
Fanconis syndrome
RTA
Hereditary or acquired Tubulointerstitial
disease

FLUID, ELECTROLYTE, AND ACID-BASE

DISORDERS

Metabolic acidosis

M
E
T
A
CI
D
O
SI
S

common disturbance in advanced CKD

combination of hyperkalemia and
hyperchloremic metabolic acidosis is often
present, even at earlier stages of CKD
(stages 13)
Treat hyperkalemia
the pH is rarely <7.35
usually be corrected with oral sodium
bicarbonate supplementation

FLUID, ELECTROLYTE, AND ACID-BASE

DISORDERS

Renal Control of Acid-Base Balance

1) Secretion of H+ and Reabsorption of HCO3 by the
Renal Tubules
M
E
T
A
CI
D
O
SI
S

a. H+ is Secreted by Secondary Active Transport in the Early

Tubular Segments
b. Filtered HCO3 is Reabsorbed by Interaction with H+ in the
Tubules
c. Primary Active Secretion of H+ in the Intercalated Cells
of Late Distal and Collecting Tubules

2) Combination of Excess H+ with Phosphate and

Ammonia Buffers in the Tubule Generates New
HCO3
a. Phosphate Buffer System Carries Excess H+ into the Urine
and Generates New HCO3
b. Excretion of Excess H+ and Generation of New HCO3 by
the Ammonia Buffer System

Renal Handling of Acid

Excretion

 To maintain euvolemia:

Adjustments in the dietary intake of salt

and use of loop diuretics, occasionally in combination with
metolazone

Hyponatremia:

water restriction

Hyperkalemia

responds to dietary restriction of potassium,

avoidance of potassium supplements
use of kaliuretic diuretics
potassium-binding resins, such as calcium resonium or
sodium
polystyrene

The renal tubular acidosis and subsequent

anion-gap metabolic acidosis

alkali supplementation, typically

with sodium bicarbonate

DISORDERS OF CALCIUM AND PHOSPHATE

METABOLISM
The principal complications of abnormalities
of calcium and phosphate metabolism in CKD
1.
occur in the skeleton and
2.
the vascular bed,
3.
with occasional severe involvement of
extraosseous soft tissues
Bone manifestations of CKD, classified as:
. associated with high bone turnover with
increased PTH levels
. low bone turnover with low or normal PTH
levels

DISORDERS OF CALCIUM AND PHOSPHATE

METABOLISM
The pathophysiology of secondary
hyperparathyroidism:
1.
Declining GFR leads to reduced excretion of
phosphate
2.
increased synthesis of PTH and growth of
parathyroid gland mass
3.
decreased levels of ionized calcium,
resulting from diminished calcitriol production by
the failing kidney

Fibroblast growth factor 23 (FGF-23)

(1)

increased renal phosphate excretion;

(2) stimulation of PTH, which also increases renal
phosphate excretion; and
(3) suppression of the formation of 1,25(OH)2D3,
leading to diminished phosphorus absorption from the

DISORDERS OF CALCIUM AND PHOSPHATE

METABOLISM

Osteitis fibrosa cystica

bone turnover
abnormal histology
brown tumor

Low-turnover bone disease can be

grouped into two categories:
1.
adynamic bone disease
2. and osteomalacia

DISORDERS OF CALCIUM AND PHOSPHATE

METABOLISM

Calcium, phosphorus, and the

cardiovascular system:
Hyperphosphatemia and hypercalcemia
are associated with increased vascular
calcification
calcification of the media in coronary
arteries and even heart valves
ingested calcium cannot be deposited
in bones with low turnover
osteoporosis and vascular calcification
hyperphosphatemia can induce a change
in gene expression in vascular cells

DISORDERS OF CALCIUM AND PHOSPHATE

METABOLISM

Other complications of abnormal

mineral metabolism:
Calciphylaxis (calcific uremic
arteriolopathy)

Other etiologies

use of oral calcium as a phosphate

binder
Warfarin

Sevelamer and lanthanum non calcium

containing polymers

Calcitriol exerts a direct suppressive effect

on PTH secretion and also indirectly suppresses PTH
secretion by raising the concentration of ionized calcium

recommended target PTH level between 150

and 300 pg/mL

CARDIOVASCULAR ABNORMALITIES

1) Ischemic vascular disease

The CKD-related risk factors comprise
1. anemia,
2. hyperphosphatemia,
3. hyperparathyroidism,
4. sleep apnea, and
5. generalized inflammation
Cardiac troponin levels are frequently
elevated in CKD without evidence of acute
ischemia.

CARDIOVASCULAR ABNORMALITIES

2) Heart failure
bat wing distribution - form of lowpressure pulmonary edema

CARDIOVASCULAR ABNORMALITIES

3) Hypertension and left ventricular

hypertrophy

anemia and the placement of an

arteriovenous fistula

low blood pressure actually carries a

worse prognosis than does high blood
pressure
erythropoiesis-stimulating agents

MANAGEMENT OF HYPERTENSION

Blood pressure should be reduced to

125/75

Salt restriction should be the first

line of
therapy
MANAGEMENT OF CARDIOVASCULAR
DISEASE

Lifestyle changes, including regular

exercise

Manage dyslipidemia

Pericardial disease
Chest pain with respiratory accentuation,
accompanied by a friction rub, is diagnostic of
pericarditis.
Classic electrocardiographic abnormalities include
PR-interval depression and diffuse STsegment elevation

Initiation of dialysis
No heparin

HEMATOLOGIC ABNORMALITIES
Anemia
A normocytic, normochromic anemia is
observed as early as stage 3 CKD and is almost
universal by stage 4.
The primary cause in patients with CKD is
insufficient production of erythropoietin
(EPO) by the diseased kidneys.

Causes of Anemia in CKD

1.
2.
3.
4.
5.
6.
7.
8.
9.

Relative deficiency of erythropoietin

Diminished red blood cell survival
Bleeding diathesis
Iron deficiency
Hyperparathyroidism/bone marrow fibrosis
Chronic inflammation
Folate or vitamin B12 deficiency
Hemoglobinopathy
Comorbid conditions: hypo/hyperthyroidism,
pregnancy, HIV-associated disease, autoimmune
disease, immunosuppressive drugs

recombinant human EPO and modified EPO

Products
Use of EPO in CKD may be associated with
an:
1. increased risk of stroke in those with type 2
diabetes,
2. an increase in thromboembolic events,
3. and perhaps a faster progression to the need
for dialysis
target a hemoglobin concentration of 100
115 g/L

HEMATOLOGIC ABNORMALITIES
Abnormal hemostasis
1. prolonged bleeding time,
2. decreased activity of platelet factor III,
3. abnormal platelet aggregation and
adhesiveness,
4. and impaired prothrombin consumption.
Clinical manifestations include
5. an increased tendency to bleeding and
bruising,
6. prolonged bleeding from surgical incisions,
7. menorrhagia,
8. and spontaneous GI bleeding

Abnormal bleeding time and coagulopathy in

patients with renal failure may be reversed
temporarily with
desmopressin(DDAVP),
cryoprecipitate,
IV conjugated estrogens,
blood transfusions, and
EPO therapy.
Optimal dialysis will usually correct a prolonged
bleeding time.

NEUROMUSCULAR ABNORMALITIES
Central nervous system (CNS), peripheral, and
autonomic neuropathy
mild disturbances in memory and concentration
and sleep disturbance.
Neuromuscular irritability, including hiccups,
cramps,
and fasciculations or twitching of muscles,
becomes evident at later stages.
In advanced untreated kidney failure, asterixis,
myoclonus,
seizures, and coma can be seen

GASTROINTESTINAL AND NUTRITIONAL

ABNORMALITIES

Uremic fetor , a urine-like odor on the breath,

derives from the breakdown of urea to ammonia in
saliva and is often associated with an unpleasant
metallic taste (dysgeusia)

DERMATOLOGIC ABNORMALITIES

Pruritus
nephrogenic
fibrosing dermopathy

EVALUATION AND MANAGEMENT OF PATIENTS

WITH CKD

Laboratory investigation
Serial measurements of renal function
Serum concentrations of calcium, phosphorus,
vitamin D, and PTH should be measured to
evaluate
metabolic bone disease.
Hemoglobin concentration, iron, B 12 , and
Folate
A 24-h urine collection

EVALUATION AND MANAGEMENT OF PATIENTS

WITH CKD

Imaging studies
most useful imaging study is a renal ultrasound
CKD with normal sized kidneys
DM nephropathy
amyloidosis
HIV nephropathy
voiding cystogram
judicious administration of sodium bicarbonatecontaining solutions and N -acetyl-cysteine

ESTABLISHING THE DIAGNOSIS AND ETIOLOGY OF

CKD

Renal biopsy
Contraindications:

bilaterally small kidneys

uncontrolled hypertension,

active urinary tract infection,

bleeding diathesis (including ongoing

anticoagulation),

and severe obesity

EVALUATION AND MANAGEMENT OF PATIENTS

WITH CKD
The most important initial diagnostic step in the
evaluation of a patient presenting with elevated
serum creatinine is to distinguish newly
diagnosed CKD from acute or subacute renal
failure
SUGGESTS CHRONICITY
1.
hyperphosphatemia,
2.
hypocalcemia,
3.
elevated PTH and bone alkaline
Phosphatase
4.
Normochromic, normocytic anemia
5.
bilaterally reduced kidney size <8.5
cm

Topic Outline
IV

TREATMENT

A.SLOWING THE PROGRESSION OF CKD

1. Reducing Intraglomerular Hypertension and
Proteinuria
B.SLOWING PROGRESSION OF DIABETIC RENAL DISEASE
1. Control of Blood Glucose
2. Control of Blood Pressure and Proteinuria
3. Protein Restriction
C.MANAGING OTHER COMPLICATIONS OF CHRONIC KIDNEY
DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement Therapy
3. Patient Education

TREATMENT

TREATMENT
Any acceleration in the rate of decline should prompt
a search for superimposed acute or subacute
processes that may be reversible
1.
2.
3.
4.
5.
6.
7.

ECFV depletion,
uncontrolled hypertension,
urinary tract infection,
new obstructive uropathy,
exposure to nephrotoxic agents
and reactivation or flare of the original
disease, such as lupus or vasculitis

TREATMENT
SLOWING THE PROGRESSION OF CKD:
Reducing Intraglomerular Hypertension
and Proteinuria
renoprotective effect of antihypertensive medications
- proteinuria
125/75 mmHg as the target blood pressure
ACE inhibitors and ARBs
Adverse effects from these agents include cough and
angioedema with ACE inhibitors, anaphylaxis, and
hyperkalemia with either class
2nd line - diltiazem and verapamil

TREATMENT
SLOWING PROGRESSION OF DIABETIC
RENAL DISEASE
Control of Blood Glucose
preprandial glucose be kept in the 5.07.2
mmol/L, (90130 mg/dL)
hemoglobin A 1C should be < 7%
use and dose of oral hypoglycemic needs to be
reevaluated
Chlorpropramide
Metformin
Thiazolidinediones

TREATMENT
SLOWING PROGRESSION OF DIABETIC
RENAL DISEASE
Control of Blood Pressure and Proteinuria

albuminuria
a strong predictor of cardiovascular events
and nephropathy

Microalbumin testing
At least ANNUALLY

TREATMENT
SLOWING PROGRESSION OF DIABETIC
RENAL DISEASE
Protein Restriction

CKD 0.60 and 0.75 g/kg per day

at least 50% of the protein intake be of
high biologic value
Stage 5 CKD - 0.9g/kg/day
Caloric requirement 35cal/kg/day

TREATMENT
MANAGING OTHER COMPLICATIONS OF
CHRONIC KIDNEY DISEASE
1. Medication Dose Adjustment
loading dose no dose adjustment
>70% excretion is by a nonrenal route
no adjustment
NSAIDs should be avoided
Nephrotoxic medical imaging radiocontrast
agents and gadolinium should be avoided
http://www.globalrph.com/renaldosing2.htm

TREATMENT
MANAGING OTHER COMPLICATIONS OF
CHRONIC KIDNEY DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement Therapy

symptoms and signs of impending uremia, such

as anorexia, nausea, vomiting, lassitude RX
with Protein restriction
optimal time for initiation of renal replacement
therapy have been established KDOQI
Delaying worse prognosis

HEMODIALYSIS
ABSOLUTE INDICATIONS:
Uremic pericarditis or pleuritis
Uremic encephalopathy

Common indications:
1. Declining nutritional status
2. Persistent or difficult to treat volume
overload
3. Fatigue and malaise
4. Mild cognitive impairment
5. Refractory acidosis, hyperkalemia, and
hyperphosphatemia

TREATMENT
MANAGING OTHER COMPLICATIONS OF
CHRONIC KIDNEY DISEASE
1. Medication Dose Adjustment
2. Preparation for Renal Replacement
Therapy
3. Patient Education
Kidney transplantation - offers the best potential
for complete rehabilitation

THANK YOU

PRETEST

1) Urine albumin per gram of creatinine

content that signifies Chronic Renal
Damage:
A.17mg in males, 25mg in females
B.25mg in males, 17mg in females
C. 25mg in both sexes
D. None of the above

PRETEST

2) In CKD with Uremia, these compounds

with a molecular mass between 500 and
1500 Da, are also retained and contribute to
morbidity and mortality
A. Guanidino compounds
B. products of nucleic acid metabolism
C. Polyamines
D.middle molecules

PRETEST

3) Diuretics used in combination of loop

diuretics, which inhibits the sodium
chloride co-transporter in the distal
convoluted tubule, can help effect renal
salt excretion:
A. Ethacrynic acid
B.Metolazone
C. Acetazolamide
D. Eplerenone

PRETEST

4) The combination of ACE inhibitor and

ARB is associated with a greater

reduction in proteinuria compared to
either agent alone.

True or False

PRETEST

5) Testing for microalbumin is

recommended in all diabetic patients at

least:
A. Every
B. Every
C. Every
D. Every

6 months
3 months
12 months
clinic visit

PRETEST

6) CKD is defined by the presence of

kidney damage or decreased kidney
function, irrespective of the cause, for
at least:
A.2 months
B.3 months
C.6 months
D. 12 months

PRETEST

7) In CKD dietary recommendation, at least

how much of the protein intake should be of
high biologic value:
A. 50%
B. 40%
C. 60%
D. 30%

PRETEST

8) In CKD, NO dose adjustment is needed for

agents/drugs that are excreted by a nonrenal
route by more than:
A. 50%
B. 60%
C. 70%
D. 80%

PRETEST

9) In CKD, educational programs should be

commenced no later than stage __ CKD so that the
patient has sufficient time and cognitive
function to learn the important concepts, to make
informed choices, and implement preparatory
measures for renal replacement therapy.

A. Stage 2
B. Stage 3
C. Stage 4
D. Stage 5

PRETEST

10) Parathyroid hormone(PTH) itself is

considered a uremic toxin.

True or False

Renal Potassium
Handling

Renal Calcium and

Phosphate Handling

Chronic Kidney Disease

Leading Categories of Etiologies

of CKD

Chronic Kidney
Disease
NEPHROLOGY ROUNDS

Jose Socrates M. Evardone

Year Level 2
Nephrology 2

Renal Potassium
Handling

Normal Lab Values