Steroid-free immunosuppression in kidney-islet transplantation: a long-term follow-up

Islet transplantation has until recently been hampered by the use of glucocorticoids for immunosuppression which aggravates the metabolic demand in insulin-resistant patients. We consequently applied our success with steroid-free immunosuppression in kidney transplantation (1) to our combined kidney-islet transplantation protocol, and published in 1995 our initial results in this field using a pioneering steroid-free approach, thymoglobulin induction, and cyclosporine + mycophenolate mofetil maintenance therapy (2). Last year Shapiro et al. (3) published a series on seven patients using a similar protocol with a glucocorticoid-free immunosuppressive regimen consisting of sirolimus, tacrolimus, and daclizumab, and obtaining insulin independence in all, with a follow-up on 4.4 to 14.9 months. This series was recently expanded to 12, with a follow-up on median 10.2 months; however, only a few are observed more than 1 year (the longest was 20 months) (4). Because islet transplantation is still experimental, we find it may be of interest to report a 6-year follow-up on our first patient who had a simultaneous kidney-islet transplantation (and a second islet transplantation after 1 week). He received 9360 islet-equivalents per kg and obtained insulin-independence for more than 1 year (Fig. 1). The immunosuppressive protocol included a 10-day thymoglobulin induction together with sandimmune neoral and the patient has since been maintained on cyclosporine supplemented with mycophenolate mofetil when this drug was available 10 months after the transplantation. He had never received steroids. After 15 months he had to receive a small insulin dose. After more than 6 years of excellent kidney function (SE-creatinine 162 μmol/liter), he still has a fasting C-peptide level on 207 pmol/liter, and receives today 24 IU of insulin (40 IU before transplantation) with the same level of HbA1C as before transplantation (8.8–9.3%). He has a good quality of life and is working full time. Our patient was then one of the few who obtained sustained insulin independence. Insulin had later to be reinstituted; however, the islets are still functioning after more than 6 years with a reduced insulin requirement and well-being for the patient compared with the pretransplant situation. We did not have access to mycophenolate mofetil from the time of transplantation, which could be the reason for the declining islet function. We still think that steroid-free protocols with a combination of other immunosuppressive drugs are the way ahead; however, this long-term observation raises concerns that current conclusions about the success of such protocols in achieving long-term insulin independence may be premature.