Path to Kidney Disease in NIDDM Patients Revealed

National Institute of Diabetes, and Digestive and Kidney DiseasesEMBARGOED FOR RELEASE, Wednesday, Nov. 27, 1996, 5:00 PM Eastern Time, Sharon Ricks, Jane DeMouy

Excretion of protein in the urine is the best predictor of progressive kidney failure in people with noninsulin-dependent diabetes mellitus, or Type 2 diabetes, according to an NIH study published in the November 28 New England Journal of Medicine.

The kidney filters the body's blood, retaining most of the proteins and essential nutrients but allowing the waste-products to pass into the urine. Scientists know that in people with insulin-dependent, or Type 1 diabetes, kidney function, including the amount of blood the kidney filters, (the glomerular filtration rate or GFR), rises sharply. In some instances, albumin, a normal blood protein, appears in the urine in quantities ranging from small (microalbuminuria) to large (proteinuria). Based on some experimental animal studies, increased GFR "overworks" the kidney and sets in motion a series of self-destructive processes leading to kidney failure. Other models suggest that additional, currently undefined, types of injury cause proteinuria. Thus, proteinuria rather than elevated GFR, would be the true herald of deteriorating kidney function.

"We wanted to know whether a rise in GFR occurs in Type 2 diabetes and if it is this rise or the presence of albumin in the urine that best predicts progressive kidney failure," says Robert Nelson, M.D., an expert in the Diabetic Renal Disease Study Group at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the NIH.

The study found that the GFR rises substantially and appears to remain elevated for years in people with Type 2 diabetes. However, it is the amount of albumin that passes across the kidney's glomerular blood vessels and is excreted in the urine which predicts progressive kidney failure. The study also found that the course of kidney disease in Type 2 diabetes mimics that of Type 1.

"Clinicians will be very interested in these data," says Dr. James Balow, Clinical Director at NIDDK. "A third of the patients with end-stage renal disease have diabetes, and most of them have Type 2. This study gives us a better understanding of the natural history and predictors of progressive kidney disease in these patients."

The four-year study involved 194 Pima Indians in Arizona's Gila River Indian Community, because Pima Indians have the world's highest prevalence of Type 2 diabetes and 20 times more end-stage renal disease than the general U.S. population. Researchers measured blood flow to the kidney, the GFR, urinary albumin excretion and blood pressure in people without diabetes and in people with well-defined stages of Type 2 diabetes and kidney disease.

The GFR increased at the earliest stages of Type 2 diabetes and remained high both in those who didn't develop kidney damage as well as those who began to excrete small amounts of albumin in the urine. Deterioration of kidney function ensued only when large amounts of albumin began to be excreted in the urine. High blood pressure in patients with microalbuminuria seemed to predispose to the development of proteinuria, and presumably kidney failure.

"Prior to proteinuria, kidney structure is mostly unchanged, but in patients with heavy proteinuria, there's substantial kidney damage and a rapid decline in function," explains Nelson.

Scientists do not know what causes albumin to be excreted in the urine, but previous studies indicate that people with small amounts of albumin in the urine are at much greater risk of progressing to proteinuria and finally, to kidney failure.

Currently, the American Diabetes Association recommends that all patients with Type 1 or Type 2 diabetes be screened regularly for microalbuminuria. Early detection makes it possible to improve metabolic control and regulate blood pressure, which may effectively slow the progress of kidney disease.