Chronic Kidney Disease

dr. Tjatur Winarsanto SpPD

 Chronic Kidney Disease
Definition
Chronic, irreversible loss of kidney function attributable
to loss of functional nephron mass pathophysiologic
processes for more than 3 months.
 Pathophysiology of CKD
Final Common Pathway is loss of nephron mass

Diabetes
Hypertension Mediated by vasoactive
Loss of Structural/ Functional
Chronic GN molecules, cytokines
Nephron Mass Hypertrophy of remnant nephrons and growth factors,
Cystic Disease
Tubulointerstitial disease renin angiotensin axis

Sclerosis
of remnant
nephrons
 Estimation of GFR
Modification of Diet in Renal Disease (MDRD)
Formula
Estimated GFR = 1.86 (Serum Creat) -1.154 X (age) -0.203
Multiply by 0.742 for women
Multiply by 1.21 for African Americans

Cockroft Gault Formula

(140 age) X Body Weight (Kg)
72 X Serum Creatinine (mg/dL)
Multiply by 0.85 for women
 Staging of Chronic Kidney
Disease
Stage Description GFR (ml/min/1.73 m2)

At increased risk 90 (with CKD risk factors)

1 Kidney damage with normal or increased 90

GFR
2 Mildly decreased GFR 60-89

3 Moderately decreased GFR 30-59

4 Severely decreased GFR 15-29

5 Renal Failure <15 (or dialysis)

 Who is at Risk for CKD?
Family history of heritable renal disease
Diabetes
Hypertension
Auto-immune disease
Old age
Prior episode of ARF
Current evidence of renal damage, even with
normal or increased GFR
 Etiology and Epidemiology
6% of the US population has CKD (Stage 1 and 2)
Additional 4-5% have Stage 3 and 4 CKD
Diabetic nephropathy
Hypertension chronic ischemic nephropathy
Very high CV disease burden
 Monitoring of CKD
Serial measurements of
Creatinine
GFR
Albumin
Albumin-creatinine ratio in the 1 st morning sample
Electrolytes including HCO3, Ca, Phos; alkaline
phosphatase, iron studies, intact PTH
Renal sonogram
Renal biopsy
 Symptoms of CKD
Stage 1 and 2
Asymptomatic, hypertension
Stage 3 and 4
Anemia loss of energy
Decreasing appetite; poor nutrition
Abnormalities in Calcium, Phosphorus metabolism
Sodium, water, potassium and acid base abnormalities

Stage 5
All of the above accentuated; eventually overt uremia
 Common Causes and
Presentation

Cause Clinical Presentation

Diabetic kidney History of diabetes, proteinuria and retinopathy

disease
Hypertension Elevated BP, normal UA, family history

Non diabetic Nephritic or nephrotic presentations

glomerular disease
Cystic kidney Urinary symptoms, abnormal sediment, radiologic findings
disease
Tubulointerstitial UTI, reflux, chronic med use, drugs, imaging abnormalities,
disease urine concentrating defects
Clinical Features of Diabetic CKD
Clinical Features of Non-Diabetic
CKD
 Pathophysiology of Uremia
Azotemia refers to the retention of nitrogenous
waste products. Uremia advanced stages of
azotemia with end organ dysfunction
Accumulation of products of protein metabolism
Urea anorexia, malaise, vomiting and headaches
Loss of other renal functions
Erythropoietin deficiency anemia
Metabolic bone disease; endocrine abnormalities
Fluid, electrolyte and acid base disorders
 Symptoms of Uremia
Organ System Symptoms Signs

General Fatigue, weakness Sallow-appearing, chronically ill

Skin Pruritus, easy bruisability Pallor, ecchymoses,
excoriations, edema, xerosis
ENT Metallic taste in mouth, epistaxis Urinous breath / fetor
Eye Pale conjunctiva
Pulmonary Shortness of breath Rales, pleural effusion
Cardiovascular Dyspnea on exertion, retrosternal pain on Hypertension, cardiomegaly,
inspiration (pericarditis) friction rub
Gastrointestinal Anorexia, nausea, vomiting, hiccups
Genitourinary Nocturia, impotence Isosthenuria
Neuromuscular Restless legs, numbness and cramps in
legs
Neurologic Generalized irritability and inability to Stupor, asterixis, myoclonus,
concentrate, decreased libido peripheral neuropathy
 Mineral Metabolism
Calciphylaxis
Calcemic uremic arteriopathy
Extraosseous/metastatic
calcification of soft tissues and
blood vessels
Devastating complication
Treatment: controversial
Sodium thiosulfate
Parathyroidectomy
Cardiovascular Abnormalities
Leading cause of
morbidity and mortality in
patients with CKD at all
stages
Ischemic CAD
Hypertension and LVH
Congestive heart failure
Uremic pericarditis
 Hematological Abnormalities
Anemia
Chronic blood loss, hemolysis, marrow suppression by uremic
factors, and reduced renal production of EPO
Normocytic, normochromic
Rx: Iron and Epo as needed
Coagulopathy
Mainly platelet dysfunction decreased activity of platelet factor
III, abnormal platelet aggregation and adhesiveness and
impaired thrombin consumption
Increased propensity to bleed post surgical, GI Tract,
pericardial sac, intracranial
Increased thrombotic tendency nephrotic syndrome
 Other Abnormalities
Neuromuscular
Central, peripheral and autonomic neuropathy
Peripheral Sensory/Motor Neuropathy
Stage 4 for more than 6 months
Restless leg syndrome
Gastrointestinal
Uremic fetor
Gastritis, peptic disease, mucosal ulcerations, AVMs
Endocrine
Glucose metabolism
Estrogen levels amenorrhea, frequent abortions
Male: oligospermia, germinal cell dysplasia, delayed sexual maturation
Dermatologic
Pallor, ecchymoses, hematomas, calciphylaxis, pruritus, uremic frost
 Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
 Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
 Therapeutics in CKD
Non Pharmacologic
Risk Factor Modification
Pharmacologic
Treatment of complications
Sodium and water Imbalance
Glomerulotubular feedback is
disrupted sodium retention,
contributes to hypertension;
hyponatremia is unusual.
Higher than usual doses for
diuretics. In situations with
volume depletion can be
severe, because of inadequate
sodium retention.
Treatment: Salt restriction; high
doses of diuretics
 Potassium Imbalance
Potassium
GI excretion is augmented
Constipation, dietary intake, protein catabolism,
hemolysis, hemorrhage, transfusion of stored blood,
metabolic acidosis,
Drugs: ACE inhibitors, ARBs, B blockers, K sparing
diuretics and NSAIDs
Hyporeninemic hypoaldosteronism: Diabetes, sickle
cell disease
 Acid Base Imbalance
Damaged kidneys are unable to excrete the 1 mEq/kg/d
of acid generated by metabolism of dietary proteins.
NH3 production is limited because of loss of nephron mass
Decreased filtration of titrable acids sulfates, phosphates
Decreased proximal tubular bicarb reabsorption, decreased
positive H ion secretion
Arterial pH: 7.33 - 7.37; serum HCO3 rarely below 15
buffering offered by bone calcium carbonate and
phosphate
Should be maintained over 21
Treatment: Sodium bicarbonate, calcium carbonate,
sodium citrate
Bone Disease
 Treatment of Secondary
Hyperparathyroidism
Phosphorus control in diet
Phosphate binders
Calcium acetate (Phoslo), calcium carbonate (TUMS),
sevelamer (Renagel) , lanthanum (Fosrenol)
Oral Vitamin D
Calcimemetic agent: Cinacalcet (Sensipar)