Does Losartan Prevent Progression of Early Diabetic Nephropathy in American Indians With Type 2 Diabetes?

  1. Sudha K. Iyengar2
  1. 1Divisions of Nephrology and Endocrinology, Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California
  2. 2Departments of Genetics and Ophthalmology, Case Western Reserve University, Cleveland, Ohio.
  1. Corresponding author: Susanne B. Nicholas, sunicholas{at}

Approximately 346 million individuals worldwide and 25.8 million individuals in the U.S. have diabetes (1,2). The high prevalence of diabetes results in a persistently increased prevalence of diabetic nephropathy, which is the leading cause of kidney failure and premature cardiovascular mortality (3). In the U.S., diabetic nephropathy is represented disproportionately in several minority populations including American Indians (4). Of the American Indian tribes in which type 2 diabetes develops at an alarming rate in children as a result of childhood obesity, the Pima Indians tend to have even higher rates of diabetic nephropathy (up to 65%; age-group 45–74 years) and concomitant end stage renal disease (ESRD; as high as 3.5 times) compared with white Americans (57). Fasting hyperglycemia and hemoglobin A1C are strong predictors of albuminuria in Pima Indians. Research has established that strict control of plasma glucose in the prediabetic stage can preempt a diagnosis of diabetes in some indigenous peoples (8). Further, in Pima Indians, the combination of macroalbuminuria and worsening estimated glomerular filtration rate (eGFR) strongly predict ESRD and death (9). Several large, well-designed clinical trials in diabetic cohorts have shown that blockade of the renin angiotensin system (RAS) prevents the progression of microalbuminuria to macroalbuminuria as well as the progression of macroalbuminuria to overt proteinuria and subsequent ESRD (1012). Despite the fact that RAS blockade has shown no effect on primary prevention of diabetic nephropathy in mainly white, normotensive, normoalbuminuric, type 1 diabetic individuals, the importance of defining the renal outcome of RAS blockade in high-risk Pima Indians in particular cannot be overstated.

Indeed, primary prevention of diabetic nephropathy in Pima Indians could potentially …

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