Nephrology Question 29 Instructor

What are the stages of diabetic nephropathy? (GFR/clinical)

Name 2 trials that show the benefit of angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) in delaying the progression of diabetic kidney disease.

Stage I: onset of diabetes, functional changes – increased GFR, increased kidney size, reversible albuminuria

Stage II: structural changes – increased GBM thickness, mesangial expansion

Stage III: early nephropathy – microalbuminuria, rising BP

Stage IV: onset of proteinuria, rising serum creatinine

Stage V: end stage renal disease (ESRD)

ACE inhibitor:
Examined the effect of the administration of placebo or captopril to patients with type 1 diabetes with overt proteinuria and a plasma creatinine concentration equal to or greater than 1.5 mg/dL (132 µmol/L). The likelihood of a doubling of the plasma creatinine concentration was reduced by more than 50 percent in the captopril group.


In the Irbesartan Diabetic Nephropathy Trial (IDNT), 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan (300 mg/day), amlodipine(10 mg/day), or placebo.

At 2.6 years, irbesartan was associated with a risk of the combined end point (doubling of the plasma creatinine, development of end-stage renal disease, or death from any cause) that was 23 and 20 percent lower than with amlodipine and placebo, respectively, and the values were 37 and 30 percent lower for doubling of the plasma creatinine. These benefits were independent of the differences in the magnitude of blood pressure reduction among the groups.

In the RENAAL trial, 1513 patients with type 2 diabetes and nephropathy were randomly assigned to losartan(50 titrating up to 100 mg once daily) or placebo, both in addition to conventional antihypertensive therapy (but not ACE inhibitors).

Compared to placebo, losartan reduced the incidence of a doubling of the plasma creatinine by 25 percent and end-stage renal disease by 28 percent; the mean follow-up was 3.4 years. These benefits were again not associated with differences in blood pressure levels between the groups.


Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med. 1993;329:1456-1462.

Lewis EJ et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001 Sep 20;345(12):851-60.

Brenner BM et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001 Sep 20;345(12):861-9.

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