MANAGEMENT OF DM IN CKD DIFFFERS AS THE OHA SHOULD BE USED CAUTIOUSLY AND ALSO INSULIN..

1. MANAGEMENT OF DIABETES MELLITUS IN CKD by Dr.SridharDM (nephrology)

2. Diabetes:TheMost Common Cause of ESRD Diabetes Hypertension 50.1% 27% Primary Diagnosis for Patients Who Start Dialysis Glomerulonephritis Other No. of patients 13% 10% 700 Projection 95% CI 600 500 400 No. of dialysis patients (thousands) 520,240 300 281,355 200 243,524 100 r2=99.8% 0 1984 1988 1992 1996 2004 2000 2008

3. Comorbidities %Stroke/TIA %Heart Failure %ASHD %Amputation/PVD

4. Causes of renal disease in diabetes Diabetic nephropathy Renal artery stenosis Myeloma, outflow obstruction, polycystic renal disease, glomerulonephritis, etc Drugs NSAIDS/Cox 2 inhibitors Fibrates ACEI, ARBs

5. Diabetic Nephropathy 30% of all end-stage renal disease Increased co-morbidity and mortality – retinopathy, cardiovascular disease, stroke, peripheral vascular disease May be prevented/delayed by early screening and treatment

10. Factors affecting progression of nephropathy Blood pressure Urinary protein excretion (glycaemic control)

11. Minimum screening for renal disease in Diabetes Annual EMU for ACR. Repeat within a month if positive, in absence of UTI/renal stones/other renal disease Annual serum creatinine Creatinine eGFR(preferred MDRD equation)

12. microalbuminuriaand proteinuria Diagnosis of microalbuminuria based on 2 out of 3 positive first passed morning urine samples in absence of urinary tract infection

13. Initial assessment of patient with diabetes and renal impairment Is this likely to be diabetic nephropathy? Presence of retinopathy Microalbuminuria/proteinuria Is this likely to be renal artery stenosis? Family history, Drug history, GU history etc AIP, myeloma screen, PSA Ultrasound

14. Metformin Metformin has been used in low doses in patients with glomerular filtration rate (GFR) as low as 30 to 60 ml/min. It should not be used at a GFR below 30 ml/min -- risk for lactic acidosis. As renal function can deteriorate abruptly, better to avoid metformin once serum creatinineconcentration rises above 1.5 mg/dl (132 μmo/l) in men 1.3 mg/dl (117 μmol/l) in women ORAL HYPOGLYCEMICS

17. insulin Insulin regimens are the most commonly used to control glycemiain CKD increasing half-life of insulin as CKD progresses, the risk for hypoglycemia increases. Insulin requirements decrease further in HD patients, particularly in those with residual diuresis (<500 ml/day), Insulin requirement often decreases by 30% In peritoneal dialysis (PD) patients, intraperitonealinsulin is more physiologic than subcutaneous, as portal absorption of insulin may better mimic the endogenous insulin effect. Insulin requirements typically increase by 200% to 300% in this situation

18. Insulin in pt. on hemodialysis Insulin inhibitors – dialyzable Insulin resistance diminishes after the start of dialysis. half-life of insulin is prolonged. the potential for hypoglycemia with both oral agents and insulin increases in the presence of CKD (with the exception of gliquidoneand glimepiride). Self-monitoring of blood glucose concentration is imperative. Insulin requirement often decreases by ~30% Glargine has been shown to reduce hypoglycemia in hemodialysis patients

20. BLOOD PRESSURE CONTROL BP reduction in type 1 & type 2 DM patients reduces rate of CKD progression At any given level of GFR, blood pressure tends to be higher in diabetic than in nondiabeticpatients with CKD recommended blood pressure target 125/75 mm Hg Ideally – (typically takes three or four drugs to accomplish) start with an ACEinhibitor or ARB Add diuretic Add calcium channel blocker, β-blocker, or renin inhibitors

21. If Blood Pressure >125/75 mm Hg in Diabetes or Chronic Kidney Disease with Any Level of Albuminuria (if systolic BP >20 mmHg above goal) START with ACEI or ARB/thiazide diuretic*) (if systolic BP< 20 mmHg above goal) Start ARB or ACE Inhibitor titrate upwards Recheck within 2-3 weeks If BP Still Not at Goal (125/705mm Hg) Add Long Acting Thiazide Diuretic* Add CCB or b blocker** (titrate dose upward) Recheck within 2-3 weeks If BP Still Not at Goal (125/75 mm Hg) Consider low dose aldosterone antagonists# or If used CCB, Add Other Subgroup of CCB(ie, amlodipine-like agent if verapamil or diltiazem already being used and the converse) OR if b blocker used add CCB Recheck within 4 weeks If BP Still Not at Goal (125/75 mm Hg) Add Vasodilator (hydralazine, minoxidil)

24. begin at a low dose;

25. increase dose at 4-week intervals to reduce microalbuminuria

26. antiproteinuric effects not necessarily attained at antihypertensive doses

27. increase dose until proteinuria reduced by 30 to 50%

28. Titrate to maximal suppression of urinary albumin excretion for DM patients with persistent microalbuminuria despite intensive insulin therapy even without HTN

29. titration limited by adverse effects:an acute increase in serum creatinine of 50% or more; renal artery stenosis; hypovolemia; congestive heart failure hyperkalemia resistant to corrective maneuvers ARB : consider for subjects with documented aldosterone escape

30. Impact of diabetes on dialysis Blood pressure management Autonomic Insufficiency BP drops and very labile Medial Calcificaton Wide pulse pressure Hypertensive Cardiomyopathy Preload Cardiac function After load

31. Lipid control Heart Protection Study Patients with DM and CKD who received statins had a 23% decrease in cardiovascular risk with an absolute event reduction of 80% In HD patients with type 2 DM, the addition of 20 mg of atorvastatin 40% decrease in lowdensitylipoprotein cholesterol levels & significant decrease in cardiac events

32. Dosages of statins In ckd IN PT.S ON HEMODIALYSIS AND PERITONEAL DIALYSIS Atorvastatin - up to 80 mg/day Fluvastatin– up to 80 mg/day. Pravastatin- limited to 10 mg, as active metabolites can accumulate, Pravastatin Pooling Project - of up to 40 mg were safely (GFR of 30 ml/min per 1.73 m2) Simvastatin – upto 20 mg/day (40-mg/day in stage 3 CKD (Heart Protection Study)) Rosuvastatin - not more than 10 mg/day when GFR falls below 30 ml/min per 1.73 m2. Ezetimibe - safely used (effects absorption mainly bile acid sequestrants) Fenofibrate - reduced by one third in CKD stage 2, reduced by two thirds in CKD stages 3 and 4 avoided in CKD stage 5. Gemfibrozil - safely used, although in PD, elevated CPK levels have been reported Niacin(Sustained-release)- should be decreased by 50% at CKD stage 5

33. DIET IN CKD PT.S WITH DM Diabetic patients with renal failure are often severely catabolic and tend to develop malnutrition Reduction of dietary protein intake to 0.8 g/kg body weight for CKD Stages 1–4 is recommended Increase protien intake >1.2g/kg in HD >2.0g/kg in PD ANEMIA Anemia occurs at an earlier stage of CKD in DM patients and is often more severe Erythropoietin - Anemia associated with CKD In DM - higher dosages compared with nonDMpt.s

34. Diabetic patients with CKD develop secondary hyperparathyroidism at a slower rate than nondiabetics predisposed to low-turnover (adynamic) bone disease - risk factor for cardiovascular calcification care should be taken to avoid calcium loading. Accumulate aluminum more readily and are more susceptible to aluminum-induced bone disease. Aluminum containing phosphate binders should always be avoided in the diabetic patient with advanced CKD Target serum phosphorus goal < 5.5 mg/dl in patients with Stage 5 CKD < 4.6 mg/dl in Stage 3–4 CKD. if the i-PTH is abnormal - evaluate for vitamin D deficiency measurement of 25-hydroxy vitamin D.

35. Diabetic Management in ckd Parameter Lower BP……………………… Block RAAS…………………… Improve glycemia ……………. Lower LDL cholesterol……….. Anemia management ………... Endothelial protection………… Smoking……………………….. Target < 125/75 mmHg ACEi or ARB to max tolerated A1c < 6.5% (Insulin/TZD) < 100 (70) mg/dl statin + other Hb 11-12 g/dl (Epo + iron) Aspirin daily Cessation

36. RENAL replacement therapy in ckd with dm Start dialysis at eGFR - 15 ml/min per 1.73 m2 (normally - eGFR <7-8) they tend to tolerate uremia poorly and frequently have sodium retention and fluid overload. Peritoneal dialysis–associated glucose loading Replace glucose solutions in part by amino acid solutions and polyglucose. Loss of solute and water transport often limits long-term use of peritoneal dialysis to 3 to 5 years. Switching to hemodialysis should be considered before volume overload or uremic symptoms occur Pt.s on PD, Glucose meters based on GLUCOSE OXIDASE TEST should be used maltose and polyglucose present in PD solution, affect glucose dehydrogenase–based glucose meters

37. Transplants Type 1 DM - pancreas transplant Can induce regression of moderate Diabetic Nephropathy lesions in native kidneys but only during a period of 10 years after transplantation. Pancreas transplantation at the time of renal transplantation Prevents / slows the development of Diabetic Nephropathy in the transplanted kidney.

39. Thank you