Chronic Kidney Disease

Chronic Kidney Disease SERVICE 6

Chronic Kidney Disease • Stages 4-5 (GFR <30 mL/min): disturbances in water/electrolyte balance or endocrine/metabolic derangements • Interventions that have been proven to be effective include: • Strict glucose control in diabetes • Strict blood pressure control • ACE inhibition or angiotensin-2 receptor blockade

Chronic Kidney Disease • Interventions that have been studied, but the results of which are inconclusive, include: • Dietary protein restriction • Lipid-lowering therapy • Partial correction of anemia

Anemia K/DOQI 2006 • Definition of anemia: <13.5 g/dL for males, <12.0 g/dL for females • Target hemoglobin = 11.0-12.0 g/dL • Adequate iron status: serum ferritin = 100 (non-HD) to 200 (HD) μg/L and transferrin saturation ≥20%

Anemia • In general, oral iron will be sufficient to attain and maintain these targets in those not yet requiring dialysis and those on PD. • Ferrous sulfate • Used as a building block for hemoglobin synthesis • Dose: 325 mg PO qd-tid

Anemia • In contrast, many HD patients will require intravenous iron to replenish iron stores in individuals on erythropoietin therapy. • Iron dextran • Iron sucrose • Ferric gluconate

Anemia • Erythropoiesis-stimulating agents (ESA) • Non-HD: Subcutaneous • HD: Intravenous • Objective:  Hb levels by 1-2 g/dL per month

Anemia • Epoetinα • Stimulates division and differentiation of committed erythroid progenitor cells • Induces release of reticulocytes from bone marrow into bloodstream • Dose: 50-150 U/kg IV/SC 3 times/wk • Darbepoetin • Longer half-life • Dose: 0.45 mcg/kg IV/SC qwk

Calcium-Phosphate Metabolism • Phosphorus • Stages 3-4: ≥2.7 mg/dL (0.87 mmol/L) and ≤4.6 mg/dL (1.49 mmol/L) • Stage 5: 3.5-5.5 mg/dL (1.13-1.78 mmol/L) • Calcium • Target: 8.4-9.5 mg/dL (2.10-2.37 mmol/L) • The total dose of elemental calcium provided by the calcium-based phosphate binders should not exceed 1,500mg/day and the total intake of elemental calcium should not exceed 2,000 mg/day.

Calcium-Phosphate Metabolism • Calcium carbonate • For treatment of hyperphosphatemia or as a calcium supplement • Combines with dietary phosphate to form insoluble calcium phosphate • Dose: 1-2 g PO divided bid-qid (with meals as a phosphorus binder, between meals as a calcium supplement)

Calcium-Phosphate Metabolism

Calcium-Phosphate Metabolism • Calcitriol • Used to suppress parathyroid production and secretion in 2° hyperparathyroidism • For treatment of hypocalcemia [serum levels of corrected total calcium <9.5 mg/dL (2.37 mmol/L) and serum phosphorus <4.6 mg/dL (1.49 mmol/L)] by increasing intestinal calcium absorption • Dose: 0.25 mcg PO qd-qod ( at 4- to 8-wk intervals by 0.25 mcg/d to achieve target PTH level and to maintain serum calcium levels at 9-10 mg/dL)

Calcium-Phosphate Metabolism • Calcium-phosphorus product • Target: <55 mg2/dL2(normal value = 40 mg2/dL2) • Although the serum calcium level drops, the serum phosphorus level rises, leading to an abnormal increase in the calcium-phosphorus product, [Ca] × [Pi]. • Experimentally, even small increases in [Ca] × [Pi] may increase soft tissue calcification, including vascular tissues. • Increased [Ca] × [Pi] is associated with greater mortality in patients undergoing HD as well as with a higher increased coronary artery calcification score in such patients. • Best achieved by controlling serum levels of phosphorus within the target range

Calcium-Phosphate Metabolism • Cinacalcet • Directly lowers iPTH levels by increasing the sensitivity of calcium sensing receptors on the chief cells of the parathyroid gland to extracellular calcium • Results in concomitant serum calcium decrease • Dose: 30 mg PO qd initially (titrate upward slowly by 30 mg increments to target iPTH of 150-300 pg/mL

Calcium-Phosphate Metabolism • Sevelamer • Binds dietary phosphate in the intestine, thus inhibiting its absorption • Decreases the frequency of hypercalcemic episodes • Dose: 800-1600 mg PO tid with meals (/ by 400-800 mg per meal every 2 wks to maintain serum phosphorus ≤6 mg/dL)

Metabolic Acidosis • Serum levels of total CO2 should be maintained at >22 mEq/L (22 mmol/L). • Sodium bicarbonate Gr X tab = 7 mEq/tab • Dose: 2-4 g/d or 25-50 mEq/d

Hyperuricemia • Reduction in the efficiency of urate excretion • Hyperuricemia is of no clinical importance with respect to CKD until serum urate levels exceed at least 13 mg/dL (773 µmol/L) in men, and 10 mg/dL (595 µmol/L) in women. • Allopurinol therapy significantly decreases serum uric acid levels in hyperuricemic patients with mild to moderate CKD. • Helps preserve kidney function during 12 months of therapy compared with controls

Dyslipidemia

Hypertension

Evaluation of the patient with CKD Does the Pt have diabetic kidney disease? OR Does the Pt have nondiabetic kidney disease with spot urine total protein-to-creatinine ratio ≥200 mg/g? YES NO Periodically re-evaluate Can an ACEI or ARB be introduced or increased? Is BP <130/80 mmHg? NO YES YES NO Introduce or increase ACEI or ARB Introduce or increase diuretic or other agent Monitor response, including proteinuria, and manage side effects

Nutrition • Serum albumin is a valid and clinically useful measure of protein-energy nutritional status in maintenance dialysis patients. • The recommended daily energy intake is 35 kcal/kg/d for those who are less than 60 years of age and 30-35 kcal/kg/d for individuals 60 years or older.

Nutrition • The recommended DPI for clinically stable HD patients is 1.2 g/kg/d. At least 50% of the dietary protein should be of high biological value. • For individuals who are not undergoing maintenance dialysis, the institution of a planned low-protein diet providing 0.60 g protein/kg/d (up to 0.75 g protein/kg/d) should be considered.

Renal Replacement Therapy • Severe metabolic acidosis • Hyperkalemia • Pericarditis • Encephalopathy • Intractable volume overload • Failure to thrive and malnutrition • Peripheral neuropathy • Intractable gastrointestinal symptoms • GFR <10 mL/min

Chronic Kidney Disease