CHRONIC

KIDNEY
DISEASE

by
Hasyim kasim
 Definition of Chronic Kidney Disease
Criteria
1. Kidney damage for ≥ 3 months, as defined by structural or functional
abnormalities of the kidney, with or without decreased GFR,
manifest by either :
• Pathological abnormalities, or
• Markers of kidney damage, including abnormalities in the composition
of the blood or urine, or abnormalities in imaging tests

2. GFR < 60 mL/min/1.73 m2 for ≥ 3 months, with or without

kidney damage

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

 Chronic Kidney Disease : A Clinical Action Plan

Stage Description GFR

(mL/min/1.73m2)
At increased risk ≥ 90 (with CKD
risk factors)
1 Kidney damage with normal ≥ 90
or ↓ GFR
2 Kidney damage with mild ↓ GFR 60-89

3 Moderate ↓ GFR 30-59

4 Severe ↓ GFR 15-29

5 Kidney failure < 15

(or dialysis)

Shaded area identifies patients who have CKD; unshaded area designates individuals
who are at increased risk for developing CKD
Am J Kidney Dis 2002 ; 39 (suppl 1) : S19.
 EPIDEMIOLOGY

• The Third National Health and Nutrition Examination

Survey (NHANES III), 2003, USA :
Stadium 1 : 3.3%
Stadium 2 : 3%
Stadium 3 : 4.3%
Stadium 4 : 0.2%
Stadium 5 : 0.2%

Overall : 11%
The Relationship of Blood Urea Nitrogen (BUN) or
Serum Creatinine Concentration to
Glomerular Filtration Rate.

The broken lines indicate that there is a family of curves rather than a single one for all patients
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 = or Ccr =
85 × Pcr (mg/dl) Pcr (mol/L)

Age – years
Weight – Kg
Pcr – plasma creatinine
The formula estimates Ccr in obese patients and those on a low protein diet
Rate of Glomerular Filtration Rate (GFR) Decline
in Normals and in Hypothetical patients with
Onset of The Progressive of Renal Disease
at Age 25
 Evaluation and Treatment
Patients with chronic kidney disease should be evaluated
to determine :
• Diagnosis (type of kidney disease)
• Comorbid conditions
• Severity, assessed by level of kidney function
• Complications, related to level of kidney functions
• Risk for loss of kidney function
• Risk for cardiovascular disease

Am J Kidney Dis 2002 ; 39 (suppl 1) : S24.

 Classification of CKD
by Pathology, Etiology and
Prevalence in patients with
ESRD
 Evaluation and Treatment
Treatment of chronic kidney disease should include :

• Spesific therapy, based on diagnosis

• Evaluation and management of co-morbid conditions
• Slowing the loss of kidney function
• Prevention and treatment of cardiovascular disease
• Prevention and treatment of complications of decreased kidney function
• Preparation for kidney failure and kidney replacement therapy
• Replacement of kidney function by dialysis and transplantation, if sign and
symptoms of uremia are present

Am J Kidney Dis 2002 ; 39 (suppl 1) : S24.

 Potential Risk Factors for Susceptibility to
and Initiation of Chronic Kidney Disease

Clinical Factors Sociodemographic

Factors

Diabetes Older age

Hypertension
Autoimmune diseases US ethnic minority status:
Systemic infections African American, American Indian,
Urinary tract infections Hispanic, Asian or Pasific Islander
Urinary stones
Lower urinary tract obstruction Exposure to certain chemical and
Neoplasma Environmental conditions
Family history of CKD
Recovery from acute renal failure Low income / education
Reduction in kidney mass
Exposure to certain drugs
Low birth weight
Am J Kidney Dis 2002 ; 39 (suppl 1) : S73.
Individuals at increased risk for CKD should be
tested at the time of a health evaluations to
determine if they have CKD.

• Diabetes
• Hypertension
• Autoimmune diseases
• Systemic infections
• Exposure to drugs or procedures associated with acute
decline in kidney function
• Recovery from acute kidney failure
• Age > 60 years
• Family history of kidney disease
• Reduced kidney mass (includes kidney donors and
transplant recipients)
Measurements should included :

• Serum creatinine for estimation of GFR

• Assessment of proteinuria
• Urinary sediment of urine dipstick for red blood
cells and white blood cells
 Clinical Manifestation of
Chronic Renal Insufficiency (1)

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 Renal Insufficiency (2)
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 Renal Insufficiency (3)
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 Renal Insufficiency (4)

Electrolytes
Bone Abnormalities
Hyperkalemia
Osteomalacia
Hyponatremia
Osteitis fibrosa
Hyperphosphatemia
Osteosclerosis
Hypocalcaemia
Aluminum associated
Hyperuricaemia
osteomalacia
Metabolic Acidosis
Progression of renal disease :

A irreversible decline in GFR because

of structural damage to the renal
vasculature, tubules or interstitium.
Risk factors for acute decline in GFR on
chronic kidney disease. :

• Volume depletion
• Intravenous radiographic contrast
• Selected antimicrobial agents (i.e.: aminoglycosides
and ampotericin B)
• NSAIDs, including cyclo-oxygenase type 2 (COX 2)
inhibitors
• ACE-inhibitors and ARB
• Cyclosporine and tacrolimus
• Obstruction of the urinary tract
 Definitions of Progression, Remission, and
Regression of Proteinuric Chronic Nephropathy

Variable Progression Remission Regression

Proteinuria ≥ 1g/24 h < 1g/ 24 h < 0.3g / 24 h

Glomerular filtration rate Declining Stable Increasing

Renal structural changes Worsering Stable Improving

Ruggenenti P, et al. Lancet 2001 ; 357 : 1602.

Pivotal role of glomerular hypertension in the
initiation and progression of structural injury
Aging
Primary Renal Disease
Systemic Hypertension Diabetes Mellitus
Renal Ablation
Dietary Factor

GLOMERULAR HYPERTENSION

ENDOTHELIAL INJURY MESANGIAL INJURY

EPITHELIAL INJURY
Release of vasoactive factors Accumulation of macromolecules
Vascular lipid deposition Matrix production Proteinuria
Intracapillary throbosis Cell proliteration Permeability to water

GLOMERULAR SCLEROSIS
Brenner B M
 THE MECHANISM OF PROGRESSION OF
CHRONIC KIDNEY DISEASE

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 = LEVEL 1
= LEVEL 2
9. SMOKING
= LEVEL 3
10. NSAID
11. ANEMIA
Hebert LA, et al : Kidney Int 2001; 59 : 804
 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.
 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
Aims of Dietary protein restriction :

• To slow the progression of kidney disease

• Minimize accumulation of uremic toxins
• Preserve protein nutritional status
• CKD stages 1-3 (GFR > 30 mL/min) :
- Protein 0.75 g/kg/d
• CKD stages 4-5 (GFR < 30 mL/min) :
- Protein 0.6 g/kg/d
 Chronic Kidney Disease : A Clinical Action Plan

Stage Description GFR Action

(mL/min/1.73m2)
At increased risk ≥ 90 (with CKD Screening, CKD risk
risk factors) reduction
1 Kidney damage with normal ≥ 90 Diagnosis and
treatment, treatment
or ↓ GFR
of comorbid
conditions, slowing
progression, CVD risk
reduction
2 Kidney damage with mild ↓ 60-89 Estimating
GFR progression
3 Moderate ↓ GFR 30-59 Evaluating and
treating complications
4 Severe ↓ GFR 15-29 Preparation for kidney
replacement therapy
5 Kidney failure < 15 Replacement
(or dialysis) (if uremia present)
Shaded area identifies patients who have CKD; unshaded area designates individuals
who are at increased risk for developing CKD Am J Kidney Dis 2002 ; 39 (suppl 1) : S19.
 Components of Optimal Care by NKF Stages of CKD

Stage 1 Stage 2 Stage 3 Stage 4 Stage 5

Components of (GFR ≥ 90 Mild CKD Moderate Severe CKD Kidney
ml/min/1. (GFR 60-89 CKD (GFR 30- (GFR 15-29 Failure
CKD Care 73 m2) ml/min/1.73 59 ml/min/1.7 (GFR <15
m2) ml/min/1.73 3 m2) ml/min/1.
m2) 73 m2)

Diagnosis and treatment Yes Yes Yes Yes Yes

Treatment of cormobid conditions Yes Yes Yes Yes Yes
Slowing progression Yes Yes Yes Yes -
CVD risk reduction Yes Yes Yes Yes Yes
Estimating progression - Yes Yes Yes Yes
Evaluating and treating - - Yes Yes Yes
complications
Preparation for kidney - - - Yes -
replacement therapy
Kidney replacement therapy - - - - Yes
(if uremia present)
 Impact of CVD on Survival of Patients with
End-Stage Renal Disease on Hemodialysis

1 CVD -
CVD +
0.8

Survival
0.6
probability

0.4

0.2

0
12 24 36 48 60
Months
CVD=cardiovascular disease.
Hirschl MM et al. Am J Kidney Dis. 1992;10:564-568.
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