Diabetic nephropathy is the leading cause of end-stage renal disease. About 20-30% of patients with type 1 or type 2 diabetes develop nephropathy, which involves stages of hyperfiltration, microalbuminuria, proteinuria, and finally end-stage renal disease. Risk factors include age, race, ethnicity, history of microalbuminuria, hypertension, poor glycemic control, and smoking. Treatment aims to control blood pressure and block the renin-angiotensin system using ACE inhibitors, angiotensin receptor blockers, or calcium channel blockers to slow the progression of kidney damage.

1. DIABETIC NEPHROPATHY Upendra Reddy. K 2010H146037H 4/2/2011 1

3. Accounts for over one-third of all patients who are on dialysis.

4. About 20–30% of patients with type 1 or type 2 diabetes develop evidence of nephropathy. 4/2/2011 2

6. 80 - 90% with micro albuminuria will progress to overt diabetic nephropathy in 5 - 10 years

7. nearly 100% with gross proteinuria will progress to ESRD in 7 - 10 yrs4/2/2011 3

9. 10-20% with micro albuminuria will progress to overt nephropathy.

10. Minority populations have a 2 to 20-fold higher incidence of diabetic nephropathy.4/2/2011 4

12. Hypertension

13. Poor glycemic control

14. Smoking

15. Family history of nephropathy.4/2/2011 5

17. Stage II - Glomerular lesions without clinically evident disease

18. Stage III - Incipient nephropathy withmicro albuminuria - alb/cr ratio .03 - .3 or albumin 20-200 mcg/min on timed specimen 4/2/2011 6

19. Stages of Diabetic Nephropathy II III I IV V 4/2/2011 7

20. Stage IV - Overt diabetic nephropathy with proteinuria >500 mg/24 hrcreatinineclearance <70 ml/min Stage V – End stage renal disease (ESRD) - creatinine clearance <15 ml/min - creatinine = 6mg/dl 4/2/2011 8

21. Signs & symptoms: Fatigue Protein in urine Foamy appearance/excessive frothing of urine Frequent hiccups Swelling of the legs Unintentional weight gain(from fluid build up) 4/2/2011 9

22. Diabetic nephropathy :Diagnosis & treatment

23. Screening for micro albuminuria: Measurement of the albumin-to-creatinine ratio in a random spot collection; 24-h collection with creatinine, allowing the simultaneous measurement of creatinine clearance; Timed (e.g., 4-h or overnight) collection. 4/2/2011 11

24. SCREENING FOR NEPHROPATHY WHEN: Type 1 - annually after puberty and 5 years of DM Type 2 - at diagnosis and then annually WHAT: random urine ACR; and random urine dipstick Suspicion of nondiabetic renal disease? Yes Workup or referral for nondiabetic renal disease No Normal < 2.0 mg/mmol men < 2.8 mg/mmol women Rescreen in 1 year Macroalbuminuria > 20 mg/mmol men > 28 mg/mmol women Diabetic nephropathy diagnosed Check ACR results Microalbuminuria 2.0 - 20 mg/mmol men 2.8 - 28 mg/mmol women Any 2 abnormal out of 3 ACRs: Diabetic nephropathy diagnosed Up to 2 repeat random urine ACRs performed 1 week to 2 months apart Only 1 abnormal ACR: Repeat screen in 1 year 4/2/2011 12

25. Treatment of Diabetic Nephropathy Hypertension Control -Goal: lower blood pressure to <130/80 mmHg ACE inhibitors: captopril, enalapril, lisinopril, benazepril, fosinopril, ramipril, quinapril, perindopril, trandolapril, moexipril Angiotensin receptor blockers(ARB) candesartan cilexetil, irbesartan, losartan potassium, telmisartan, valsartan, esprosartan 4/2/2011 13

27. Patients who develop mild to moderate hyperkalemia should receive nutritional counseling regarding a potassium-sparing diet and consideration should be given to the use of non-potassium-sparing diuretics.4/2/2011 14

29. Ongoing clinical trials: 4/2/2011 17

31. American Diabetes Association (2004). Nephropathy in diabetes. Clinical Practice Recommendations 2004. Diabetes Care. 27(Suppl 1): S79–S83

32. DeFronzo RA: Diabetic nephropathy: etiologic and therapeutic considerations. Diabetes Reviews 3:510-547, 1995

33. www.clinicaltrials.gov.in4/2/2011 18