1. Chronic Kidney Disease SERVICE 6

2. Chronic Kidney Disease Stages 4-5 (GFR <30 mL/min): disturbances in water/electrolyte balance or endocrine/metabolic derangements 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: 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

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

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

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

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

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

8. Anemia Epoetin α Epoetin α – 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 Darbepoetin – Longer half-life – Dose: 0.45 mcg/kg IV/SC qwk

9. Calcium-Phosphate Metabolism Phosphorus 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 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.

10. Calcium-Phosphate Metabolism Calcium carbonate 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)

11. Calcium-Phosphate Metabolism

12. Calcitriol 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)

13. Calcium-Phosphate Metabolism

14. Calcium-phosphorus product Calcium-phosphorus product – Target: <55 mg 2 /dL 2 (normal value = 40 mg 2 /dL 2 ) – 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

15. Calcium-Phosphate Metabolism Cinacalcet 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

16. Calcium-Phosphate Metabolism Sevelamer 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)

17. Metabolic Acidosis Serum levels of total CO2 should be maintained at >22 mEq/L (22 mmol/L). 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

18. Hyperuricemia Reduction in the efficiency of urate excretion 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. 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. 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 Helps preserve kidney function during 12 months of therapy compared with controls

19. Dyslipidemia

20. Dyslipidemia

21. Hypertension

22. Hypertension

23. 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? Can an ACEI or ARB be introduced or increased? Is BP <130/80 mmHg? Introduce or increase diuretic or other agent Introduce or increase ACEI or ARB Monitor response, including proteinuria, and manage side effects Periodically re- evaluate YES NO YES NO YES

24. Nutrition Serum albumin is a valid and clinically useful measure of protein-energy nutritional status in maintenance dialysis patients. 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. 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.

25. 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. 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. 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.

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

28. Calcium-Phosphate Metabolism