Management of chronic kidney disease

Management of chronic kidney disease

1. MANAGEMENT OF CHRONIC KIDNEY DISEASE GUIDE: DR Y. JAMRA CANDIDATE: DR NARESH PATEL

2. Definition: CKD is defined as abnormalities of kidney structure or function, present for >3 months Criteria for CKD (either of the following present for >3 months) Markers of kidney damage (one or more) Albuminuria (AER >30 mg/24 hours; ACR >30 mg/g [>3 mg/ mmol ]) Urine sediment abnormalities Electrolyte and other abnormalities due to tubular disorders Abnormalities detected by histology Structural abnormalities detected by imaging History of kidney transplantation Decreased GFR GFR <60 ml/min/1.73 m2 (GFR categories G3a–G5)

3. CKD is classified based on cause, GFR category, and albuminuria category (CGA).

4. Screening Tools: eGFR Considered the best overall index of kidney function. Normal GFR varies according to age, sex, and body size, and declines with age. The NKF(National kidney foundation) recommends using the CKD-EPI Creatinine Equation (2009) to estimate GFR. Other useful calculators related to kidney disease include MDRD and Cockroft Gault.

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6. Cockcroft-Gault Formula : Creatinine clearance = [{(140-age)* weight}/ (72*serum creatinine)] *0.85 (if female) GFR calculators are available online at www.kidney.org/GFR

7. Small changes make a big difference Lee A Hebert et al. Kidney International (2001) 59 , 1211–1226 A GFR loss of > 1 mL/min/year beginning at age 25 can result in end-stage renal disease within a normal lifespan.

8. Screening Tools: ACR Urinary albumin-to-creatinine ratio (ACR) is calculated by dividing albumin concentration in milligrams by creatinine concentration in grams. Spot urine albumin-to-creatinine ratio for quantification of proteinuria First morning void preferable 24hr urine test rarely necessary

9. Etiology of Chronic Kidney Disease

10. CKD -Clinical Manifestations Abnormal Sodium-Water metabolism Edema, Hypertension Abnormal Acid-base abnormalities Metabolic Acidosis Abnormal hematopoiesis Anemia of CKD Cardiovascular Abnormalities LVH, CAD Abnormal Calcium-Phosphorus metabolism Hyperphosphatemia, hypocalcemia Hyperparathyroidism

11. Fluid and Electrolyte disorder Patients with CKD, the tubular reabsorption of filtered sodium and water is adjusted ,so that urinary excretion matches intake. Many form of kidney disease disrupt this balance leading to sodium retention and extracellular fluid volume(ECFV) Dietary salt restriction and use of loop diuretics, occasionally in combination with metalozone maintain euvolemia In contrast overzealous salt restriction or diuretic use can lead to ECFV depletion and precipitate further decline in GFR.

12. Hyperkalemia Decline in GFR doesn’t necessarily parallel decline in urinary potassium excretion Hyperkalemia may precipitate due to increased dietary potassium intake, protein catabolism, hemolysis, blood transfusion and metabolic acidosis RAS inhibitor and potassium sparing diuretics also cause hyperkalemia. In diabetic nephropathy and renal disease involving distal nephron such as obstructive uropathy and sickle cell nephropathy are associated with earlier and more severe disruption of potassium secreting mechanism in distal nephron out of proportion to decline in GFR.

13. Hyperkalemia Treatment: Respond to reduce dietary potassium Stop potassium sparing diuretics (spironolactone) Stop or reduce beta blockers, ACE inhibitor/ARBs Hypokalemia is not common in CKD.

14. Hyperkalemia Treatment continue… Large amounts of potassium are found in: • certain fruits and vegetables (like bananas, melons, oranges, potatoes, tomatoes, dried fruits, nuts, deep- colored and leafy green vegetables, and some juices) • milk and yogurt • dried beans and peas • most salt substitutes • protein-rich foods, such as meat, poultry, pork, and fish

15. Metabolic acidosis Mild degree of non-anion gap metabolic acidosis (PH < 7.35)often present in CKD stage 1-3 With the worsening renal function non-anion gap metabolic acidosis complicated by anion gap metabolic acidosis Respond to alkali supplementation, typically with sodium bicarbonate if serum bicarbonate concentration falls below 20-23 mmol /L Correction of metabolic acidosis may slow CKD progression and improve patients functional status by attenuating catabolic state.

16. Hypertension Effective reduction in BP with antihypertensive medication can decrease the urinary excretion of albumin and slow the rate of progression of CKD Dual blockade of the renin-angiotensin system with an ACE inhibitor and angiotensin receptor blocker has been shown to have an additive effect in reducing albumin excretion. Avoid ACE inhibitor and ARB in combination because Risk of impaired kidney function and hyperkalemia

17. Blood pressure control Single most important measure to slow the progress of CKD Individualize targets and agents according to age, coexistent CVD, and other comorbidities ACE or ARB Diuretics enhance the antihypertensive and antiproteinuric effects of other agents.

18. ACEi and ARB: Slowing CKD Progression ACE inhibitor and ARBs appear to slow the decline of renal function in a manner beyond reduction in systemic blood pressure Check labs after initiation If less than 25% SCr increase, continue and monitor If more than 25% SCr increase, stop ACEi Better proteinuria suppression with low Na diet and diuretics

19. Clinical Practice Guidelines for Management of Hypertension in CKD Type of Kidney Disease Blood Pressure Target (mm Hg) Preferred Agents for CKD, with or without Hypertension Other Agents to Reduce CVD Risk and Reach Blood Pressure Target Diabetic Kidney Disease <140/90 ACE inhibitor or ARB Diuretic preferred, then BB or CCB Nondiabetic Kidney Disease with Urinary albumin-to-creatinine ratio (ACR) 3 0 mg/g <130/80 Nondiabetic Kidney Disease with Urinary albumin-to-creatinine ratio (ACR) <30 mg/g None preferred Diuretic preferred, then ACE inhibitor, ARB, BB or CCB Kidney Disease in Kidney Transplant Recipient CCB, diuretic, BB, ACE inhibitor, ARB

20. Diabetes and Glycemic Control in CKD Target HbA1c ~7.0% Improved glycemic control reduces the rate at which microalbuminuria appears and progresses Risk of hypoglycemia increases as kidney function becomes impaired Declining kidney function may necessitate changes to diabetes medications and renally -cleared drugs

21. Modification of Other CVD Risk Factors in CKD Smoking cessation Alcohol restriction For those who drink alcohol, consume </=2 drink/day in men and </= 1 drink in women Exercise 30 -60 minutes of moderate intensity dynamic exercise 4-7 days/ week. Weight reduction target BMI 18.5 – 24.9 kg/m2 and waist circumference in men <102 cm and female < 88 cm.

22. Modification of Other CVD Risk Factors in CKD Lipid lowering therapy In adults >50 yrs : statin when eGFR ≥ 60 ml/min/1.73m 2 ; :statin or statin/ezetimibe combination when eGFR < 60 ml/min/1.73m 2 In adults < 50 yrs , statin if history of known CAD, MI, DM, stroke Aspirin is indicated for secondary but not primary prevention Dietary salt restriction less than 5-6 gm daily

23. Anemia in CKD Normocytic normochromic anemia is observed as early as stage 3 CKD and is almost universal by stage 4. Diagnose anemia in adults and children >15 years with CKD when the Hb concentration is <13.0 g/l in males and <12.0 g/dl in females. Anaemia in CKD should include assessment of secondary causes including iron deficiency.

24. Anaemia continue…. Iron replacement is often effective in anaemia of CKD as initial therapy. ESA (erythropoiesis stimulating agents): Start ESA if Hb <10 g/dl, and maintain Hb <11.5 g/dl. E nsure adequate Fe stores. Before initiation of ESA therapy iron saturation should be maintained at 30 -50 % and serum ferritin at 200-500 ng/ml. In addition to iron adeqaute supply of vitamin B12 and folic acid should be assured.

25. CKD-MBD (Mineral and Bone Disorder) Serum calcium , phosphate and PTH should be measured for adults with stage 4-5 CKD and for with stage 3 CKD with progressive decline in renal functions. Serum phosphate and serum calcium level should be maintained within the normal range. Target PTH levels in CKD is 150-300 pg /ml.

26. Pathophysiology of Secondary Hyperparathyroidism Decline GFR Phosphate retention : hyperphosphatemia Increase PTH hyperparathyroidism Increase synthesis of FGF-23 by osteocytes Suppression of calcitriol production by kidney Decrease level of ionised Calcium

27. FGF-23 maintain normal serum phosphate level by Increase serum phosphate excretion Stimulation of PTH , which increase phosphate excretion Suppression of calcitriol leading to diminished phosphorus absorption from GI tract. FGF-23 is also an independent risk factor for LVH and mortality in CKD, dialysis and renal transplant patients.

28. Bone Manifestations Osteitis fibrosa cystica - due to secondary hyperparathyroidism Adynamic bone disease and osteomalcia - low or normal PTH Occasionally calcium will precipitate in soft tissue in large concentration termed “TUMORAL CALCINOSIS”

29. Calciphylaxis Calcific uremic arteriolopathy is a devasting condition seen almost in patients with advanced CKD and heralded by livedo reticularis and ischemic necrosis patches, especially in legs, thigh, abdomen and breast. Pathologically, vascular and extensive soft tissue calcification.

30. CKD-MBD :Prevention Restriction of dietary phosphate: Large amounts of phosphorus are found in: •dairy products such as milk, cheese, yogurt, ice cream, and pudding •nuts and peanut butter •dried beans and peas, such as kidney beans, split peas, and lentils •beverages such as cocoa, beer, and dark cola drinks •bran breads and bran cereals •processed, convenience, and fast foods, including some meats

31. CKD-MBD : Prevention continue… Use of calcium based phosphate binders- calcium carbonate and calcium acetate and non-calcium based phosphate binders sevalamer and lanthanum. Calcium based phosphate binder have risk of developing hypercalcemia. Prescribe vitamin D analogue if serum level of intact PTH > 53 pg /ml

32. Renal replacement therapy Indication: Uremic symptoms: anorexia and nausea, impaired nutritional status, increased sleepiness, and decreased energy level, attentiveness, and cognitive tasking Presence of Hyperkalaemia unresponsive to conservative measure Severe metabolic acidosis refractory to medical therapy Uremic pericarditis Encephalopathy Persistent extracellular volume expansion despite of diuretic therapy Asymptomatic patients with eGFR 5-9 ml/min/1.73 m2

33. Treatment Options for Renal Replacement Therapy There are essentially two options to a patient facing ESRD: 1- Dialysis 2- Transplantation, which has been clearly shown to be the best treatment option

34. Dialysis Options They have to choose between hemodialysis and peritoneal dialysis Hemodialysis can be done at home with a machine that is smaller than the traditional in-hospital/outpatient clinic machine. Peritoneal dialysis can either be done with a cycler or manually

35. Immunizations CDC recommend following immunization in patients with CKD on dialysis Influenza vaccine annually for all CKD patients Pneumococcal vaccine for patients with ESRD O, 2 months Booster at 5 year Hepatitis B vaccine O, 1,2, 6 month (2 ml)

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