Diabetes Dateline

NIDDK Researchers Seek Model for Reversing Kidney Damage

The 1990s saw significant advances in the understanding and treatment of chronic renal failure in general and diabetic nephropathy in particular. At the beginning of the decade, scientists knew that antihypertensive drugs could slow the progressive decline of renal function caused by diabetic nephropathy. In 1993, the Collaborative Study Group, funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), found that captopril, a member of the class of antihypertensives known as angiotensin-converting enzyme (ACE) inhibitors, protected renal function in patients with type 1 diabetes better than other medicines that provided the same level of blood pressure control. Subsequent studies have shown that the protection conferred by ACE inhibitors extends to patients with other types of renal disease, although it has not been determined in large populations whether the protection of renal function goes beyond that attributable to lowering blood pressure. Still, in all of these studies, treatment merely slows the progression of the disease; it does not reverse or stop it.

More recently, NIDDK-funded researchers have been exploring possible ways to actually reverse the damage done by diabetic and other nephropathies. In July 1998, one group of researchers reported observing the reversal of the lesions of diabetic nephropathy after a pancreas transplant. While the study is based on only eight cases and improvement was not observed until 10 years after transplantation, the study provides hope of reversing renal disease in patients with type 1 diabetes.

The researchers explain that diabetic nephropathy results from a buildup of extracellular material in the mesangium and membranes of the kidney filters that decreases filtration surface. In people who do not have diabetes or hyperglycemia, the volume of this extracellular material stays constant throughout their adult lives, reflecting a balance between the production of extracellular material and its removal. In some people with diabetes, hyperglycemia causes this extracellular material to build up until diabetic nephropathy results. However, since many people with diabetes do not develop nephropathy, the researchers theorize that some genetic mechanism is responsible for the different renal reactions to hyperglycemia.

In patients who achieved 10 years of good glycemic control after receiving a pancreas transplant, the volume of extracellular material had decreased, indicating a shift in the balance between the buildup and removal of this substance in and around the glomeruli.

The researchers point out that neither the mechanism that reverses extracellular buildup after a pancreas transplant nor the genetic mechanism that protects some people with diabetes from nephropathy is well understood. They assert that further research in this area will result in a greater understanding of the mechanisms that protect and restore renal function and in powerful tools for treating a range of renal diseases.

For information on upcoming diabetes-related meetings, workshops, programs, and events, check the National Diabetes Education Program's 2000 Diabetes Calendar at ndep.nih.gov/new/nltr/nltr_index.htm on the Internet.

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