Diagnosis and Treatment of Diabetic Nephropathy SFM Didactics January 14, 2003 Carol Cordy, MD

1. Diagnosis and Treatment of Diabetic NephropathySFM DidacticsJanuary 14, 2003Carol Cordy, MD

2. 1.Why should you screen for diabetic nephropathy?2. How should you screen for diabetic nephropathy?3. What should you do with the results of your screening tests?

3. Why screen? Why treat? Prevention and treatment of diabetic nephropathy can reduce the incidence of end stage renal disease and death

4. Diabetic Nephropathy and ESRD • Diabetic nephropathy is the leading cause of end stage renal disease in the United States accounting for over 40% of dialysis patients • The 5-year mortality rate for a dialysis patient is 93% • Dialysis for one patient costs over $50,000 annually

5. Epidemiology Type 1 Diabetic • 25 - 45% will develop diabetic nephropathy • 80 - 90% with microalbuminuria will progress to overt diabetic nephropathy in 5 - 10 years • nearly 100% with gross proteinuria will progress to ESRD in 7 - 10 yrs

6. Epidemiology Type 2 Diabetic • 50% will have microalbuminuria at the time of presentation probably secondary to HTN • 10-20% with microalbuminuria will progress to overt nephropathy • minority populations have a 2 to 20-fold higher incidence of diabetic nephropathy

7. Risk Factors for Diabetic Nephropathy • Age, Race, Ethnicity • History of microalbuminuria • Hypertension • Poor glycemic control • Smoking • Family history of nephropathy • genetic abnormalities of ACE gene

8. Stages of Diabetic Nephropathy • Stage I – Hyperfiltration - increased blood flow through the kidney, early renal hypertrophy • Stage II - Glomerular lesions without clinically evident disease • Stage III - Incipient nephropathy withmicroalbuminuria - alb/cr ratio .03 - .3 or albumin 20-200 mcg/min on timed specimen

9. Stages of Diabetic Nephropathy II III I IV V

10. Stages of Diabetic Nephropathy • Stage IV - Overt diabetic nephropathy with proteinuria >500 mg/24 hr - creatinine clearance <70 ml/min • Stage V – End stage renal disease (ESRD) - creatinine clearance <15 ml/min - creatinine = 6mg/dl

11. Stages of Diabetic Nephropathy II III I IV V

12. Primary care physicians have the most frequent contact with diabetic patients and therefore have the greatest potential to favorably affect their health

13. How are we doing? Studies show that primary care physicians screen only 20% oftheir diabetic patients for diabetic nephropathy

14. How are we doing? Once screened many physicians are not sure what to do with the results

15. Diabetic Nephropathy Algorithm • Evidence-based approach • Goal – The use of the algorithm will improve renal function screening in the diabetic population and encourage the initiation of appropriate therapy in patients with all stages of renal disease

16. Using the Algorithm

18. UA (Urine Dipstick) • Use as an initial screen for all patients • Negative to trace proteinuria requires further testing for microalbuminuria • 1+ or greater proteinuria requires further testing to quantitate proteinuria • Once a patient has microalbuminuria, UA (urine dipstick) testing for gross proteinuria may be adequate although yearly testing for albuminuria may have become standard of care

19. Microalbuminuria • Spot AM urine: Alb/Cr ratio .03-.3* • Timed urine collection: 20-200µg albumin/min • 24 hour urine collection: 30-300 mg albumin in 24 hours *This is the most practical test

20. Microalbumin Testing Factors that Cause False Positive Test • poorly controlled diabetes • morbid obesity • acute illness, fever, UTI • pregnancy, menstruation • high protein diet • CHF • hematuria, major stress: surgery or anesthesia

21. Incipient Nephropathy Type 1 Diabetes • 2 out of 3 urine tests + for microalbuminuria (start screening 5 years after the initial diagnosis) • presence of proliferative diabetic retinopathy • 80-90% of type 1 patients with microalbuminuria will progress to DN

22. Incipient Nephropathy Type 2 Diabetes • 2 out of 3 urine tests + for microalbuminuria (start screening at the time of diagnosis of diabetes) • presence of diabetic retinopathy • 20-30% may have diabetic nephropathy but not diabetic retinopathy • 25% may have a diagnosis of nephropathy other than diabetic nephropathy

23. Macroalbuminuria • Spot AM urine: Alb/Cr ratio greater than .3 • Timed urine collection: greater than 200µg albumin/min • 24 hour urine collection: greater than 300 mg albumin in 24 hours • If macroalbuminuria is present then test for gross proteinuria

24. Gross Proteinuria • Defined as urine protein >500mg/24 hr. • Gold standard test is • 24 hour urine collection for total protein and creatinine clearance • Can also test protein/creatinine ratio • measures total mg protein/mg creatinine • correlates 1:1 with a 24 hr urine in grams/24 hr • less accurate in ARF, intersitial nephritis, high degrees of proteinuria

25. Overt Diabetic Nephropathy • Gold Standard is biopsy • Diagnosis can be made by clinical history and exclusion of other renal disease • Workup includes • Renal ultrasound for size, shape, abnormalities • 24 hour urine for total protein and creatinine clearance

26. Treatment • Lifestyle changes • Lose weight • Stop smoking • Low salt diet for BP control • Low protein diet? • Glycemic Control • Benefit in both Type 1 and Type 2 patients • Recommended: HbA1C <7.0% (some say <6.5%)

27. Blood Pressure Control • Current ADA recommendations are for blood pressure <130/80-85 (if nephropathy <125/75) • Several randomized controlled trials indicate that improved blood pressure control decreases the rate of progression of renal disease in both type 1 and type 2 patients

28. ACE’s and ARB’s • Angiotensin converting enzyme inhibitors and angiotensin receptor blocking agents have been shown in animal models and in randomized controlled trials to improve diabetic nephropathy • Mechanism of action - ACE-inhibitors limit angiotensin II production by blocking angiotensin converting enzyme, ARB-agents block angiotensin II receptors

29. Questions for future studies • Will higher doses of ACE’s and ARB’s improve outcome and decrease microalbuminuria? • Will patients without microalbuminuria benefit from the use of ACE’s and ARB’s? • What about other BP medications for patients who cannot tolerate ACE’s and ARB’s? • Which of the newer oral agents for glucose control are also renal protective? • Is there a place for low protein diets for diabetics before renal disease develops?

30. Case #1 Your first patient is a 25 year old young man with a 5 year history of type 1 diabetes. His urine dipstick is negative for protein. You check a spot AM urine alb/cr ratio which is .019. His blood pressure is 112/66. His HbA1C is 6.9.

31. Which is (are) true? • The patient has early or incipient diabetic nephropathy. • The patient should maintain a HbA1C of less than 7 to help protect his kidneys. • You should start the patient on an ACE inhibitor to protect his kidneys. • All of the above are true.

32. Patient #2 Your next patient is a 43 year old woman with a six year history of type 2 diabetes. A urine dip shows trace protein and a spot AM urine alb/cr ratio is .039. Her blood pressure is 135/80 and her HbA1C is 6.7.

33. Which is (are) not true? • You should check the patient’s serum creatinine and potassium. • You should start the patient on an ACE inhibitor if her K+ and Cr are okay. • You should check a 24 hour urine for total protein and creatinine clearance. • The patient has overt diabetic nephropathy and should be referred to a nephrologist.

34. Case #3 Your last patient is a 60 year old with HTN, dyslipidemia and newly diagnosed type 2 diabetes. A urine dip shows 2+ protein. He has a fever and his HbA1C is 10.3. His blood pressure is 140/88. He is taking HCTZ and glipizide.

35. Which is (are) true? • You should get the patient’s diabetes under better control before rechecking his urine. • A fever will not cause proteinuria. • The patient’s blood pressure is under good control. • You should check the patient’s potassium and creatinine.

36. Case #3 Three months later with exercise, metformin and enalapril your patient’s HbA1C is now 7.5 and his blood pressure is 135/85. A urine dip now shows 1+ protein.

37. Which is (are) true? • You should check a 24 hour urine for total protein and cr. cl. • A spot AM urine albumin/creatinine ratio correlates well with a 24 hour urine for total protein • The patient likely already has diabetic nephropathy and should be referred to a nephrologist.

38. Use the Algorithm! • Check all your diabetic patients annually for renal disease . • Help your diabetic patients’ protect their kidneys by helping them keep their diabetes under control. • Help your diabetic patients protect their kidneys by helping them keep their blood pressure under control.