The Role of Kidney-Pancreas Transplantation in Diabetic Kidney Disease

Abstract

For patients with type 1 diabetes, innovations in insulin formulations and delivery have improved the ability to achieve excellent blood glucose control. However, it is uncommon to achieve euglycemia, particularly while avoiding complications arising from hypoglycemia. Pancreas transplantation remains the only broadly applied treatment strategy that can result in normalization of blood glucose, but this must be weighed against the risks of a surgical procedure and subsequent immunosuppression. To improve this risk/benefit ratio, pancreas transplantation is typically performed in patients with kidney failure who are to undergo kidney transplantation and immunosuppression (simultaneous pancreas-kidney transplant) or who have undergone kidney transplant and are obligated to the use of immunosuppressive medications (pancreas after kidney transplant). The purpose of this review is to clarify the benefit of an added pancreas transplant in these clinical settings and formulate an approach to the patient with type 1 diabetes as they approach kidney failure.

Kidney, Pancreas and Islet Transplant Options for Patients with Diabetic Nephropathy

“…Age should not be considered as an absolute contraindication for KT [32], but most transplant centers do not accept diabetic patients older than 45-50 years for SPK or PAK [11]. This is mainly due to an increased rate of surgical complications and lower graft survival rates [8][9][10], although some other studies did not confirm these results [33].…”

“…However, recent progress in immunosuppression has reduced rejection rates below 25% or even lower depending on the applied protocols in each center. Induction therapies with monoclonal or polyclonal antibodies have also reduced the incidence and the severity of the rejection episodes [6][7][8][9][10][11]. Most transplant centers have been using T cell depleting antibodies (thymoglobulin or alemtuzumab), whereas interleukin-2 receptor antibodies (basiliximab and daclizumab) have shown higher rejection rates and their use is declining (<10%) [11].…”

“…Although there is no consensus about the optimal immunosuppressive protocol in pancreas or kidney-pancreas transplantation, most authorities suggest induction therapy with depleting antibodies and maintenance therapies based on tacrolimus, sirolimus or MMF, with early or late steroid withdrawal [6][7][8][9][10][11].…”

“…This is mainly due to the higher rates of surgical complications during SPK, but this advantage starts to become less clear after 5-6 years, when the results favour the SPK procedure [71,72]. Based on a thorough review of all the available data, Wiseman [9] has recently concluded that LDKT is without doubt superior to DDKT and probably to SPK, if we consider that about 10-15% of the SPK patients may lose the pancreas allograft during the first year. However, for the remaining 85% of the SPK recipients, SPK is superior to LDKT.…”

“…However, pancreas transplantation was not fostered so easily by the transplant community due to increased rates of surgical complications and rejections of the pancreatic allografts. Gradual progress in surgical techniques and the advent of more powerful immunosuppressive agents has improved significantly the initial outcomes [5][6][7][8][9][10] and by the end of 2010 more than 35000 pancreas transplantations have been totally reported to the International Pancreas Transplant Registry (IPTR) with the vast majority (24000) performed in the US [11].…”