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Risk of Failure

Markers predict diabetes-linked loss of kidney function

Photo credit: Dr. Mark J. Winter/Photo Researchers, Inc. An accurate predictor of renal failure risk in patients with type 1 and type 2 diabetes has been discovered by HMS researchers at Joslin Diabetes Center. The predictive elements: elevated levels in the bloodstream of tumor necrosis factor receptors 1 and 2 (TNFR-1 and TNFR-2).

In two studies published March 1 in the Journal of the American Society of Nephrology, the Joslin researchers report that high concentrations of TNFR-1 and TNFR-2 can accurately predict this risk ten years in advance. Currently available clinical tests cannot identify people at risk with that level of accuracy.

Says lead author Monika A. Niewczas, an HMS instructor in medicine, “High levels of these markers multiply the risk of developing kidney complications by three to five times.” Niewczas is also a research associate in the laboratory of senior author Andrzej Krolewski, an HMS associate professor of medicine and head of Joslin’s Section on Genetics and Epidemiology.

Tumor necrosis factors are proteins involved in inflammation, and a growing body of evidence indicates that certain inflammatory mechanisms together with high blood sugar contribute to renal injury in diabetes. This study showed that elevated levels of TNFR-1 and TNFR-2 led to renal disease in diabetic patients, regardless of the presence or absence of other clinical characteristics, such as blood pressure, albuminuria (a leak of large amounts of albumin into urine), and glycated hemoglobin, that are considered important risk factors for diabetic nephropathy.

Renal complications, also known as diabetic nephropathy, are one of the most life-threatening complications of diabetes. Over time, this damage frequently leads to end-stage renal disease, when the kidneys can no longer work at the level needed to support everyday life. About a half million people in the United States have end-stage renal disease, and nearly 44 percent of these cases result from diabetes.


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