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Smad1 as a Biomarker for Diabetic Nephropathy

From the Division of Nephrology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York

Corresponding author: Katalin Susztak, MD, PhD, Division of Nephrology, Albert Einstein College of Medicine, Ullmann Bldg. 613, Bronx, NY 10461. E-mail: ksusztak@aecom.yu.edu

The first 20% of the full text of this article appears below.

Diabetic nephropathy is one of the most devastating complications of diabetes and develops in about one-third of diabetic patients. Exposure to a hyperglycemic environment with coexisting obesity, metabolic syndrome, hyperfiltration, hypertension, and hyperlipidemia plays a critical role in the development of diabetic nephropathy (1,2). Clinical trials demonstrated that improving glycemic control delays and, in some cases, may prevent the subsequent development of diabetic nephropathy. The concept that selected individuals with diabetes (at similar glycemic control) are at different risk for developing nephropathy was developed about 20 years ago after finding familial aggregation of kidney disease (3,4). Detailed phenotyping studies indicate that diabetic nephropathy progression and patients’ responses to treatment also varies significantly between individuals.

To identify patients at increased risk for the development of diabetic nephropathy, considerable scientific effort has been dedicated to developing new screening and prognostic markers (5). The hope is that these new biomarkers will predict the development of the disease earlier than the currently used disease marker, albuminuria. The problem with albuminuria as a disease marker is twofold. Low-grade albuminuria (microalbuminuria) is a poor predictor of diabetic nephropathy (6); high-grade albuminuria, which is a strong predictor of disease progression, only develops at advanced diabetic nephropathy, a stage when less can be done to prevent the development of end-stage kidney failure.

How can we identify biomarkers? Traditionally, biomarker identification has mostly been a one-at-a-time approach. Many well-known tests have been identified based on clear biological insight from physiology or biochemistry. One example of this path . . . [Full Text of this Article]

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