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Can We Prevent Diabetic Nephropathy in Type 2 Diabetes Patients?

Losartan prescribed to Pima Indians in the U.S. may help prevent diabetic nephropathy progression…. 

About 346 million individuals worldwide have diabetes. The increased prevalence of diabetes results in an increased prevalence of diabetic nephropathy. Diabetic nephropathy leads to kidney failure and premature cardiovascular mortality. Pima Indians tend to have an even higher rate of diabetic nephropathy than other ethnicities with their fasting hyperglycemia and HbA1c being reliable predictors of albuminuria.

In a recent study that included type 2 diabetic Pima Indians, a randomized, double-blinded, placebo-controlled trial of 169 participants was treated with either losartan or a placebo. The participants had had type 2 diabetes for at least 5 years and either normoalbuminuria or microalbuminuria. The primary outcome was a reduction in GFR ≤60 ml/min or ½ baseline with GFR <120 ml/min. A secondary outcome was the difference in structural changes to examine glomerular volume, filtration surface area density, fractional interstitial area, glomerular basement membrane width, and number of endothelial cells, mesangial cells.

Strengths of this study included high-risk individuals, renal-function was measured with high-performance liquid and extensive analyses were conducted. Weakness of the study was a number of participants did not reach the primary outcome. The results of this study supported previous observations in type 1 diabetes where RAS blockage with losartan did not prevent development of microalbuminuria nor did it increased mesangial fractional volume. But with the blockade of RAS, it did prevent the progression of microalbuminuria to macroalbuminuria. It also reduces the risk of GFR decline.

Results showed no difference in glomerular volume or filtration surface area density between the controlled and placebo groups. Since the participants have a high incidence of nondiabetic glomerular lesions, it is difficult to conclude that these lesions have any impact on diabetic nephropathy progression. Other questions arise such as if RAS blockade in hypertensive normoalbuminuric Pima Indians may alter disease progression. In Pima Indians, hypertension in both parents and prediabetic hypertension in an offspring can play a role in developing diabetic nephropathy.

Practice Pearls:

  • Pima Indians have high rates of diabetic nephropathy.
  • Macroalbuminuria and worsen eGFR strongly predicts ESRD and death.
  • Blockade of RAS prevents macroalbuminuria

Diabetes Care, October 2013.