Reversal of diabetic nephropathy: lessons from pancreas transplantation.

Pancreas transplantation is the only therapeutic intervention able to achieve and maintain long-term euglycemia, without risks of hypoglycemia; this makes it possible to test the impact of normoglycemia in the different stages of diabetic nephropathy. Pancreas and islet transplantation in animal models prevent the development of diabetic nephropathy lesions and ameliorate or reverse established glomerular lesions. In type 1 diabetic patients, pancreas transplantation, performed simultaneously or after kidney transplantation, has been shown to prevent the recurrence of diabetic glomerulopathy lesions. The established lesions of diabetic nephropathy have been considered to be irreversible; pancreas transplantation alone allows us to test whether this is true. To this end, we studied renal structure before and 5 and 10 years after pancreas transplantation in 8 nonuremic type 1 diabetic patients. These patients, with a long diabetes duration, had established diabetic nephropathy lesions at the time of transplantation. We report that diabetic glomerulopathy lesions, unchanged at 5 years post pancreas transplantation, significantly improved after 10 years, with complete normalization of glomerular structure in most patients. Thus this study demonstrates that the lesions of diabetic nephropathy are reversed by long-term normoglycemia and that the human kidney has the potential in humans to obtain a substantial architectural remodeling of the glomerular and tubular structures toward healing.