Diabetic Nephropathy 2009

• 1.Diabetic Nephropathy
  • Joel Michels Topf, MD Clinical Nephrologist

2.

• Year Capacity

• 192684,401

• 85,753

• 97,239

• 101,001

• 1991102,501

• 107,501

• 107,501

• 2006 107,501

• 2009 106,201

Incident ESRD 0 0 0 0 56,103 87,179 91,275 110,854117,632 3. 4. 5. Etiologies of ESRD 6. 7. 8. Diabetes, diabetic nephropathy and the epidemic raging in the U.S. 9.

• Diabetics on Dialysis: 183,706

USRDS Atlas 2005 http://diabetes.niddk.nih.gov/dm/pubs/statistics/index.htm#7 Total no of Diabetics: 23,600,000 0.78% 10. ESRD CV Mortality 11. Finne, P. JAMA 2005; 294:1782-87. 12. Diabetic nephropathy

• Progressive renal damage as a result of diabetis mellitus type I or II

• Initially, patients have increased GFR (2x normal)

• Followed by proteinuria

• Followed by progressively deteriorating GFR

13. Diabetic nephropathy

• Progressive renal damage as a result of diabetis mellitus type I or II

• Initially, patients have increased GFR (2x normal)

• Followed by proteinuria

• Followed by progressively deteriorating GFR

14. 5-10 years 15-20 years 20 years 15. Ritz E, et al. N Engl J Med 1999;341 :1127-33. 16. 220 g 240 g Size Matters Normal kidney weight is 150 g

• Diseases with large kidneys:

• Multiple Myeloma Hydronephrosis

• Amyloidosis Renal Cell Cancer

• ADPKD/ARPKD Not HIVAN

17. nodular glomerulosclerosis Kimmelstiel-Wilson lesions 18.

• One in five diabetic patients on dialysis do not have this classic pathology.

• They have ischemic nephropathy, with non-specific vascular and interstitial lesions

Ritz E, Orth SR. N Eng J Med 1999; 341:1127-33. 19. Type I Diabetes Type II Diabetes No difference in glycemic control between people who get nephropathy and those who dont Ritz E, et al. N Engl J Med 1999;341 :1127-33. Incidence of proteinuria at 25 years after diagnosis 20. Genetics

• Familial clustering

• • Diabetic family members of patients with diabetic nephropathy have an OR of 4.0

• Race

• • ESRD is 5 times more likely in African Americans with family members on dialysis from DN

• • Pima indians have very high rates of diabetic nephropathy

21. Transforming Growth Factor Beta Angiotensin II Hyperglycemia Extracellular matrix Fibrosis Scientific studies on TGF and renal disease Huang Y, Et al. Kidney International 2006; 69: 1713-4. TGF 22. Hyperfiltration

• Early finding

• Renal vasodilation

• • Causes early increases in GFR

• Later

• • Nephron loss results in compensatory hyperfiltration

• • No increase in GFR

23. Pathology 24. 25. A B C 0 years 5 years 10 years 26.

• What is microalbuminuria?

• Any albumin in the urine

• Trace protein on dipstick in afirst morning specimen

• 20-200 g/min on a timedspecimen

• 30-300 mg albumin/g creatinine

• 30-300 mg/L

• What is macroalbuminuria?

• 1+ protein on a dipstick in afirst morning specimen

• 1+ protein on a dipstick at any time

• >250 mg in 24 hours

• >3.5 g per 24 hours

Diagnosis Hyperfiltration Microalbuminuria Macroalbuminuria Renal failure Diabetes 27. Diagnosis Hyperfiltration Microalbuminuria Macroalbuminuria Renal failure Diabetes Microalbuminuria Dipstick negative Macroalbuminuria Dipstick positive 30 300 mg/d 0 MI, CVA, CV Death All-cause mortality CHF hospitalization Gerstein, H. C. et al. JAMA 2001;286:421-426. Albuminuria (mg/d) 28. Perkins BA, Et al. N Engl J Med 2003;348:2285-93. Cholesterol < 198 Triglycerides < 145 Glycemic control (hgb a1c