Chronic Kidney Disease

Sumit Kumar, MD, MPH Presbyterian Hospital, Dallas, TX

The Story of Mr. George Lopez

45 yr HM with Diabetes for 10 yrs, reasonably well controlled PMH:

Hypertension for 7 yrs..well controlled BMI of 30 Dyslipidemia

Fam Hx: Diabetes; Soc Hx: Sedentary; non smoker; Comedian Exam

139/85 Mild Obesity, rest fairly normal BUN 28, Creatinine 1.8, Urine protein (dipstick) 2+

Labs

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 Chronic GN Cystic Disease Tubulointerstitial disease

Loss of Structural/ Functional Nephron Mass Hypertrophy of remnant nephrons

Mediated by vasoactive molecules, cytokines and growth factors, 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 At increased risk 1 2 3 4 5 Kidney damage with normal or increased GFR Mildly decreased GFR Moderately decreased GFR Severely decreased GFR Renal Failure GFR (ml/min/1.73 m2) 90 (with CKD risk factors) 90 60-89 30-59 15-29 <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

MDRD GFR for Mr Lopez

Diabetic, Hypertension, Metabolic Syndrome X Stage 3 CKD GFR = 44 ml/min/1.73 m2

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 1st 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

Estimates of Subgroups at Increased Risk for CKD

Subgroup Age > 70 yrs (8.8%) Hypertensive Patient (20%) Ethnicity (14.6%) Family History of ESRD Estimated Numbers 24 Million 50 Million ? 38 Million ? 2 Million

1992-93

1997-98

Steady Rise in the Rate of CKD in Medicare population over the last decade

2002-03

Common Causes and Presentation

Cause Clinical Presentation

Diabetic kidney disease

Hypertension

History of diabetes, proteinuria and retinopathy

Elevated BP, normal UA, family history

Non diabetic Nephritic or nephrotic presentations glomerular disease Cystic kidney disease Tubulointerstitial disease Urinary symptoms, abnormal sediment, radiologic findings UTI, reflux, chronic med use, drugs, imaging abnormalities, urine concentrating defects

Genetic Considerations
Autosomal dominant PKD Alports hereditary nephritis Familial FSGS Nephronopthisis Medullary cystic kidney disease Fabrys disease

Natural History of CKD

Most CKD has a logarithmic progression and is predictable

Mr. Lopez Progressive Decline

1.6 1.4 1.2

1/Cr Function

1 0.8 0.6 0.4 0.2 0 1998 1999 2000 2001 2002 2003 2004

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 Skin ENT Eye Pulmonary Cardiovascular Gastrointestinal Genitourinary Neuromuscular Neurologic

Fatigue, weakness Pruritus, easy bruisability Metallic taste in mouth, epistaxis Shortness of breath Dyspnea on exertion, retrosternal pain on inspiration (pericarditis) Anorexia, nausea, vomiting, hiccups Nocturia, impotence Restless legs, numbness and cramps in legs Generalized irritability and inability to concentrate, decreased libido

Sallow-appearing, chronically ill Pallor, ecchymoses, excoriations, edema, xerosis Urinous breath / fetor Pale conjunctiva Rales, pleural effusion Hypertension, cardiomegaly, friction rub Isosthenuria

Stupor, asterixis, myoclonus, peripheral neuropathy

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)

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

Trends in the interactions of diabetes, congestive heart failure, & CKD: 20022003

LVH and dilated CM are the most ominous risk factors for excess mortality and morbidity

High cardiac output Extracellular fluid overloa AV shunt Anemia

Medicare: general Medicare CKD patients continuously enrolled in Medicare Parts A & B for two consecutive years (numbers estimated from 5 percent sample)

Cardiac Complications

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
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

Coagulopathy

Other Abnormalities

Neuromuscular

Central, peripheral and autonomic neuropathy Peripheral Sensory/Motor Neuropathy Stage 4 for more than 6 months Restless leg syndrome
Uremic fetor Gastritis, peptic disease, mucosal ulcerations, AVMs Glucose metabolism Estrogen levels amenorrhea, frequent abortions Male: oligospermia, germinal cell dysplasia, delayed sexual maturation Pallor, ecchymoses, hematomas, calciphylaxis, pruritus, uremic frost

Gastrointestinal

Endocrine

Dermatologic

Uremic 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

Therapeutics in CKD

Non Pharmacologic

Risk Factor Modification

Pharmacologic Treatment of complications