Is diabetic nephropathy reversible?

The lesions of diabetic nephropathy have been considered to be irreversible. Pancreas transplantation is the only available treatment able to restore long-term normoglycemia without exposing the patients to the risks of severe hypoglycemia; thus allowing testing the effects of very long-term euglycemia in preventing, halting and reversing diabetic nephropathy. Pancreas transplantation, performed simultaneously or shortly after kidney transplantation in patients with type 1 diabetes prevents the recurrence of diabetic glomerulopathy lesions. To test whether diabetic nephropathy lesions are reversible in humans, we studied renal structure before and 5 and 10 years after pancreas transplantation alone in eight non-uremic patients with long-term type 1 diabetes, who had mild to advanced diabetic nephropathy lesions at the time of transplantation. We observed that, despite prolonged normoglycemia, diabetic glomerular lesions were not significantly changed at 5 years post pancreas transplantation. In contrast, glomerular lesions were markedly improved after 10 years; indeed in most patients glomerular structure was normal at 10-year follow-up. We reported similar findings also for tubular and interstitial lesions. Thus this study demonstrated, for the first time in humans, that the lesions of diabetic nephropathy are reversible and that the kidney can undergo substantial architectural remodeling upon long-term normalization of the diabetic milieu.