Chronic Kidney DiseaseRafael Joseph C. Villarica

Chronic Kidney Disease• abnormal kidney function • progressive decline in glomerular filtration rate

Classification of CKDStage GFR, mL/min per

1.73 m2

0 >901 >/=902 60-893 30-594 15-295 <15

Pathophysiology of CKD• Mechanisms of Damage• Initiating mechanisms specific to the underlying etiology • Set of progressive mechanisms (hyperfiltration and hypertrophy)

Risk Factors• Hypertension • Diabetes mellitus• Autoimmune disease• Older age• African ancestry• Family history of renal disease• Previous episode of acute kidney injury• Presence of proteinuria• Abnormal urinary sediment• Structural abnormalities of the urinary tract

Estimation of GFR

Estimation of GFR• GFR peaks during the 3rd decade of life (120 mL/min per 1.73 m2) • Annual mean decline in GFR is 1mL/min per year• At age 70, GFR mean value becomes 70mL/min • Mean GFR is lower in women than in men

Estimation of GFR• Albuminuria• 24-hour urine collection – standard • Spot first morning urine

• Males - >17mg of albumin per gram of creatinine• Females - >25mg of albumin per gram of creatinine

Stages 1 and 2• Not associated with any symptoms due to a decrease in GFR

Stages 3 and 4• Complications become more prominent• Anemia – easy fatigability• Decreasing appetite• Abnormalities in calcium, phosphorous and mineral regulating

hormones• Abnormalities in Na, K, water and acid-base homeostasis

Stage 5• Uremic syndrome• Renal replacement therapy is needed

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

Sodium and Water Homeostasis• Total-body content of sodium and water is modestly increased• Dietary intake of sodium > urinary excretion• Sodium retention and attendant ECFV expansion

Potassium Homeostasis• Hyperkalemia• Increased dietary potassium intake• Protein catabolism• Hemolysis• Hemorrhage• Transfusion of stored red blood cells• Metabolic acidosis• ACE, ARBS and spironolactone

Metabolic Acidosis• Less ammonia is produced• Less protons is excreted

Treatment: Fluid, Electrolyte, and Acid-Base Disorders• Adjustments in the dietary intake of salt • Loop diuretics• Renal replacement therapy• Avoidance of K in diet• Avoidance of K supplements and K-retaining medications• Kaliuretic diuretics• Sodium bicarbonate

Bone Manifestations of CKD• The pathophysiology of secondary hyperparathyroidism and the

consequent high-turnover bone disease is related to abnormal mineral metabolism • (1) declining GFR leads to phosphate retention• (2) the retained phosphate stimulates increased synthesis of PTH and growth

of parathyroid gland mass• (3) decreased levels of ionized calcium also stimulate PTH production.

Bone Manifestations of CKD• Hyperparathyroidism stimulates bone turnover - osteitis fibrosa

cystica• include bone pain and fragility• brown tumors• compression syndromes• Tumors• erythropoietin resistance

Other Complications of Abnormal Mineral Metabolism• Calciphylaxis – heralded by livido reticularis → patches of ischemic

necrosis

Treatment: Disorders of Calcium and Phosphate Metabolism• Low phosphate diet• Phosphate-binding agents (calcium acetate, calcium carbonate)• Calcitriol

Cardiovascular Abnormalities• Leading cause of morbidity and mortality• Ischemic Vascular Disease• Heart failure• Hypertension and LVH

Treatment: Cardiovascular Abnormalities• Management of Hypertension• to slow the progression of the kidney disease itself• to prevent the extrarenal complications of high blood pressure

• Salt restriction – first line of therapy• ACE inhibitors • ARBs

Treatment: Cardiovascular Abnormalities• Management of Cardiovascular Disease• Lifestyle change• Statins

Anemia

Treatment: Anemia• Recombinant human EPO • Modified EPO products• Blood transfusion• Iron supplementation

Abnormal Hemostasis• Prolonged bleeding time• Decreased activity of platelet factor III• Abnormal platelet aggregation and adhesiveness• Impaired prothrombin consumption

Treatment: Abnormal Hemostasis• Desmopressin• Cryoprecipitate• Blood transfusion• EPO therapy

Neuromuscular Abnormalities• Central nervous system (CNS), peripheral, and autonomic neuropathy• Abnormalities in muscle structure and function • Early manifestations

• Memory and concentration• Sleep disturbance

• Late manifestations• Neuromuscular irritability

• Advanced• Asterixis• Myoclonus, seizures• Coma

Gastrointestinal and Nutritional Abnormalities• Uremic fetor• Dysguesa• Gastritis, PUD and mucosal ulcerations• Constipation• Anorexia, nausea, vomiting

Endocrine-Metabolic Disturbances• Glucose metabolism is impaired• Plasma levels of insulin are slightly to moderately elevated• Menstrual abdnormalities• Spontaneous abortion

Dermatologic Abnormalities• Pruritus• Pigmentation• Nephrogenic fibrosing dermopathy

Laboratory Investigation• CBC• Urinalysis• Serum albumin levels• Lipid profile

Evidence of Renal-Bone Disease • Serum phosphate• 25-hydroxyvitamin D• Alkaline phosphatase• Intact PTH levels

Others• Serum and urine protein electrophoresis• ANA, anti DS DNA• Complement levels• C-ANCA, P-ANCA• Anti-GBM• Hepatitis B and C• HIV• VDRL

Imaging• Renal ultrasonography• Retrograde pyelography• CT scan• MRI• Renal radionuclide scanning

• Biopsy