Nephropathy

The lesions of diabetic nephropathy (DN) are usually considered to be irreversible. Pancreas transplantation is the only available treatment able to consistently restore long-term normoglycemia without exposing the patients to the risks of severe hypo- and hyperglycemia; thus allowing testing the effects of very long-term euglycemia in preventing, halting, and reversing DN. Pancreas and islet transplantation in animal models have been shown to prevent, ameliorate, or reverse the development of DN lesions. Pancreas transplantation, performed simultaneously or shortly after kidney transplantation in patients with type 1 diabetes, prevents the recurrence of diabetic glomerulopathy lesions. To determine if DN lesions are reversible in humans, the renal structure was examined in several studies before and 5 and 10 years after pancreas transplantation alone (PTA) in non-uremic patients with long-term type 1 diabetes and mild-to-advanced DN lesions at the time of transplantation. Despite prolonged normoglycemia, diabetic glomerular lesions were not significantly changed at 5 years after PTA. In contrast, glomerular lesions were markedly improved after 10 years: in most patients, the glomerular structure was normal at 10-year follow-up despite the continued administration of calcineurin inhibitors. Similar findings were observed for tubular and interstitial lesions. These studies in PTA recipients demonstrate that the lesions of DN are reversible after successful pancreas transplantation. Moreover, the kidney can undergo substantial architectural remodeling upon long-term normalization of the diabetic milieu. Clinical outcome results have shown that both simultaneous pancreas and kidney transplantation (SPK) and pancreas after kidney transplantation (PAK) compared with kidney transplantation alone in diabetic recipients significantly improve long-term kidney allograft and patient survival long term by establishing normoglycemia and metabolic control.