Haerani Rasyid

Nephrology and Hypertension Division,

Department of Internal Medicine
Medical Faculty Hasanuddin University
 Normal GFR 120 ml/min/1.73m2 In a day 210 L of water is filtered
Only 20% nephrons work at a time 2 L /day of urine is excreted
NPs

Na excretion
Water retention

Na reabsorbtion
Ca reabsorption,
PO4 excretion
Vit D synthesis
 Vasoconstriction

Angiotensin
Renin II

EPO
Sodium Aldosteron
Reabsorbtion

Vitamin D
Calcium
Calcium and absorbtion
Phosphate
Phosphate
Reabsorbtion
absorbtion

Ca release
Bone Red blood cells PO4 release
marrow
CKD – Increased Death CKD at a glance

 CKD – A Global Pandemic

 CKD 1-2 are asymptomatic
 10 million people of CKD
 Term ‘CRF’ no longer used
 Dialysis ↑ death rate 100 x
 Small ↑ in Creatinin - ↑ ↑ in
CV
 World Population is 6.65 Billion
CKD (Stages 3-5): ≈ 200 - 333 million
1. Doctors do not realize that CKD is hidden in their
patients of DM, HT and in elderly people
2. Most doctors screen less than 10% of their clinic
patients for CKD in its early stages
3. Patients are refered very late to nephrologists especially
after the CKD is irreversible
4. Only < 1/4 of people with identified CKD get an ACE
Inhibitor
All are true - all over the globe
< 0.5 %

5- 10%
LET US LEARN ABOUT CKD
1. Azotemia - Elevated blood urea nitrogen - Biochemical
(BUN >28 mg/dl) and creatinine (Cr >1.5mg/dl)-
2. Uremia is Azotemia + symptoms or signs of renal failure
3. End Stage Renal Disease (ESRD) - Uremia requiring
transplantation or dialysis (Renal replacement therapy)
4. Chronic Renal Failure (CRF) - Irreversible kidney
dysfunction with azotemia >3 months – now not used
5. Creatinine Clearance (CCr) - The rate of filtration of
creatinine by the kidney (a marker of GFR)
6. Glomerular Filtration Rate (GFR) - The total rate of
filtration of fluid from blood by the kidney
1. Either GFR < 60 ml/min/1.73m2 for  3 mon or
2. Kidney damage for  3 mon as manifested by
a. Persistent microalbuminuria / macroproteinuria
b. Biochemical abnormalities in RFT
c. Persistent non-urological hematuria
d. Structural renal abnormalities by USG
e. Biopsy proven Glomerulonephritis (rarely
needed)
(Any one of the above evidences)
 Damage for three or more months, as defined
by structural or functional abnormalities of the
kidney, with or without decreased GFR,
manifested by pathologic abnormalities or
markers of kidney damage, including
abnormalities in the composition of the blood or
urine or abnormalities in imaging tests
 GFR < 60 mL per minute per 1.73 m2 for three
months or more, with or without kidney damage

Am J Kidney Dis 2002;39(2 suppl 1):S18.

 Etiologi CKD
Etiologi 1989 * 1996 2000

Glomerulonephritis 40,12% 46,19% 39,64%

Obstruction 36,7% 12,85% 13,44%
Diabetic nephropaty 6,13% 18,65% 17,54%
Lupus nephritis 4,17% 0,16% 0,23%
Polycystic KD 2,12% 1,41% 2,51%
Hypertension 2,09% 8,46% 15,72%
Unknown 9,32% 15,2% 10,93%

Nephrology Centre in Indonesia

Sidabutar RP ( 1989 ) *
Methods of Glomerular Filtration
Rate (GFR) Measurement

Inulin Clearance
Alternative Filtration Markers
125I-Iothalamate, 51Cr-EDTA, 99mTc-DTPA and
non-radioactive iohexol
Plasma Creatinine
Creatinine Clearance
Predictive Creatinine Clearance (the Cockroft-Gault Formula)
 Creatinine Clearance

Ucr x V
Ccr =
Pcr

Pcr = Plasma concentration of creatinine

Ucr = Urine concentration of creatinine
V = Urine flow rate

Note (V) : 24 hr collection

Over night collection
Time collection
 Estimated creatinine clearence (Ccr) with
respect age, gender and body weight

Cockcroft – Gault Formula

Men
(140-age)(weight) 1.23 (140-age)(weight)
Ccr = or Ccr =
72 × Pcr (mg/dl) Pcr (mol/L)
Women
(140-age)(weight) 1.04 (140-age)(weight)
Ccr = Ccr =
85 × Pcr (mg/dl) Pcr (mol/L)
or
Age – years
Weight – Kg
Pcr – plasma creatinine
The formula estimates Ccr in obese patients and those on a low protein diet

MDRD
MODIFIED DIET RENAL DISEASE
NORMAL INCREASED RISK DAMAGE LOW GFR

CKD
DEATH RENAL FAILURE
COMPLICATIONS
CKD eGFR Other Features Suggested Management
Stage (mL/1.73
cm2)
1 90+ Normal renal function but Observation, control of BP. Consider
urine dipstick investigation for cause of urine
abnormalities or known dipstick abnormalities
structural abnormality if
renal tract or diagnosis
of genetic kidney disease

2 60-89 Mildly reduced renal Observation, control of BP.

function plus Management of cardiovascular risk
urine/structural factors. Consider investigation for
abnormalities or cause of renal impairment
diagnosis of genetic
kidney disease
3 30-59 Moderately reduced renal Observation, control of BP.
function Management of cardiovascular risk
factors. Measure Ca2+, PO4, PTH, Hb
and cholesterol. The patient may
need treatment for anaemia or
secondary/tertiary
hyperparathyroidism.
4 15-29 Severely reduced renal Regular observation, control of
function BP and CVS risk factors. Measure
Ca2+, PO4, PTH, Hb and
cholesterol. Management as for
stage 3. Preparation for ESRF
with an early decision on the
preferred mode of RRT.
5 <15 End-stage renal failure Can be managed conservatively
but RRT should be considered
for most patients (i.e. provision
of dialysis or transplantation

BP: blood pressure; CVS: cardiovascular system; Hb: hemoglobin;

PTH: parathyroid hormone; RRT: renal replacement therapy
Chronic Kidney Disease - Stages
 Diabetes
 Hypertension
 Age , Family H/o Kidney Disease
 Systemic Infections
 Recurrent UTI
 Urinary Stone Disease
 Loss of Renal mass
 Neoplasia of any part
 Nephrotoxic Drugs (NSAIDs)
Racial differences in CKD
Caucasians (Whites) 1.0 X
Asians (Indians) 1.3 X
Hispanics (Spanish) 1.5 X
Native Americans 2.0 X
Africans (Blacks) 3.8 X
* Renal injury  destruksi nefron yang bersifat
chronic progressive , irreversible

* Penurunan jumlah massa nefron menyebabkan

perubahan struktur dan hiper fungsi dari sisa nefron

* Respon mekanisme  predisposisi sklerosis nefron

 CKD

* uremia  sindrom klinik yang mengenai seluruh

organ / sistim
 Pathophysiology
Nitrogen and Lipid Metabolism
▪ Pts are often hypercatabolic and have a
decrease capacity to eliminate nitrogenous
end products of protein catabolism.
▪ Hypertriglyceridemia and, decreased HDL
are common in pts with CRF.
▪ High incidence of premature
atherosclerosis
 Clinical Manifestation of
Chronic kidney disease

Neurologic Abnormalities
Central
Cognitive change
Lethargy Cardiovascular Abnormalities
Stupor Hypertension
Coma Pericarditis
Peripheral Accelerated atherosclerosis
Motor neuropathy Vascular calcifications
Sensory neuropathy
Myoclonus
Fasciculations
 Clinical Manifestation of
Chronic kidney disease
Hematologic Abnormalities
Anemia
Leukocyte & lymphocyte dysfunction
Platelet defect

Gastrointestinal Abnormalities
Anorexia, nausea, vomiting
Gastroparesis
Hypomotility of bowel
Mucosal bleeding

Dermatologic Abnormalities
Pruritis
Calcium-phosphate
deposition
 Clinical Manifestation of
Chronic kidney disease
Rheumatologic Abnormalities
Myopathy
Calcific bursitis
Avascular necrosis
Carpal tunnel syndrome
Articular amyloid deposition
Metabolic Abnormalities
Glucose intolerance
Hyperparatiroidism
Vitamin D deficiency
Hyperlipidemia
Sexual dysfunction
Malnutrition
Pleural-Pulmonary Abnormalities
Pleuritis and effusion
Parenchymal calcification
Edema
 Clinical Manifestation of
Chronic kidney disease)

Electrolytes
Bone Abnormalities
Hyperkalemia
Osteomalacia
Hyponatremia
Osteitis fibrosa
Hyperphosphatemia
Osteosclerosis
Hypocalcaemia
Aluminum associated
Hyperuricaemia
osteomalacia
Metabolic Acidosis
 • Risk factors – CVD, DM, HT, Met. Syndro.
1 • Age, Smoking, F H/o CKD, BMI, NSAID

• Serum Creatinine, eGFR

2 • Proteinuria, U.Cr, ACR

• Urine for RBC, Casts, Crystals, Na.

3 • Serum Electrolytes, Ca, Ph, iPTH, FENa

• USG, Renal Angio only in select cases

4
1. HYPERTENSION 12. HYPERINSULINEMIA
2. PROTEINURIA 13. HOMOCYSTEINEMIA
3. ANGIOTENSIN-II 14. HYPERPHOSPHATEMIA
4. HYPERGLYCEMIA. 15. POTASSIUM DEPLETION
5. PROTEIN INTAKE 16. HYPERCOAGULATION
6. SODIUM INTAKE 17. GENDER
7. WATER INTAKE
8. HYPERLIPIDEMIA
9. SMOKING
10. NSAID = LEVEL 1
11. ANEMIA = LEVEL 2
= LEVEL 3

Hebert LA, et al : Kidney Int 2001; 59 : 804

 Interventions to slow To be avoided to prevent
progression of CKD acute reduction in GFR
1. Glycemic control in DM 1. Volume depletion
2. BP control ACEI / ARB 2. Radiographic contrast
3. Protein restriction 3. Antibiotics / NSAIDS
4. Lipid lowering therapy 4. Cyclosporine / tacrolimus
5. Weight reduction 5. ACEI / ARB if Cr > 3.5mg
6. Anemia Rx, Smoking 6. Obstructive uropathy
 FLOW CHART
SERUM CREATININE DEMOGRAPHIC DATA

GFR
STAGE 5 STAGE 3
GFR < 15 GFR 30 - 59

STAGE 4
GFR 15 - 29
 EVALUATION

1. Diagnosis
2. Co morbid conditions
3. Severity
4. Complications related to GFR
5. Risk for further loss of GFR
6. Risk for cardiovascular disease
 TREATMENT

1. Specific therapy based on diagnosis

2. E & M of co morbid conditions
3. Slowing the loss of kidney function
4. Prevention and tx of CV disease
5. Prevention and tx of complications of low GFR
6. Preparation for RRT
7. Dialysis / Transplant
 Interventions to slow the progression of
chronic kidney disease should be considered
in all patients with CKD
• Interventions that have been proven to be effective
include :

(1) Strict glucose control in diabetes

(2) Stric blood pressure control
(3) Angiotensin-converting enzyme inhibitor or angiotensin-2
receptor blockade

• Interventions that have been studied, but the

results of which are inconclusive, include :

(1) Dietary protein restriction

(2) Lipid-lowering therapy
(3) Partial correction of anemia Am J Kidney Dis 2002 ; 39 (suppl 1) : S30.
Uremia : diit protein 0,8 – 0,6 gr / kg bb / hari
Hiperkalemia : diit rendah kalium ; 60 – 80 meq/hari
Asidosis metabolik : diit rendah protein / fosfat; HCO3

Stop rokok
Kontrol lipid ( preparat statin )
HbA1C < 7 %

Hipertensi
Anemia
Osteodistrofi renal
Komplikasi kardiovaskuler
hypertension

K/DOQI, 2004 / ADA, 2003 / JNC 7, 2003 : Target BP 130/80 mmHg

Lifestyle modification : DASH diet, exercise, etc
Agent is ARB, ACE-inh (initial) : Hypertension Diabetic Kidney Disease and
Nondiabetic Kidney Disease

Hypertension and Antihypertensive Agents in Diabetic Kidney Disease

(K/DOQI)

Clinical Target BP Preffered Agents for Other Agents to Reduce

Assessment CKD CVD Risk and Reach
Target BP

BP >130/80 mmHg <130/80 mmHg ACE inhibitor or ARB A Diuretic preffered, then A
beta blocker or calcium
chanel blocker dh la

BP <130/80 mmHg ACE inhibitor or ARB A

BP < 125 / 75 mmHg ( ekskresi protein > 1 gr / hari )

Anemia

Target hematocrit pre-dialysis , hemodialysis

Relieve symptom, low risk side effect :
 Hb 9,5 g% / Ht 29 - Hb 11g% / Ht 33% ( Pernefri/NKF-DOQI)
 - erithropoetin
- preparat - iron ( bila kadar serum iron kurang )

improvements in the quality of life, cardiacfunction, Defisiensi Eritropoetin pada GGK

physical work capacity, cognitive function, and sexual
function have been reported at a hematocrit
of 36% to39%.
 Renoprotective Strategies Recommendation

1. Control blood pressure

2. ACE inhibitor therapy
Angiotensin receptor blocker (ARB) if ACE
inhibitor
intolerant
3. Control blood glucose in diabetes
4. Dietary interventions
Protein intake, NaCl intake
Fluid intake
5. Control blood lipids
6. No cigarette smoking
7. Avoid regular use of NSAIDs
8. Correct anemia
9. Control hyperphosphatemia

Hebert LA, et al : Kidney Int 2001; 59 : 1215