Immunosuppression minimization in kidney transplantation

Kidney transplantation is considered the best treatment for patients with end-stage renal failure, even in extreme age-groups. Immunosuppression for “life” is, however, mandatory. This chronic, somewhat unselected, inhibition of the host immune system may induce complications, such as cancer and infection, that could counterbalance the benefits achieved by the transplant. In addition, all currently used immunosuppressors have several side-effects, impeding their long-term use. Consequently, drug associations are frequently tested by different centres according to their own practices, resulting in different survival and tolerance profiles. Corticosteroids and calcineurin inhibitors are the cornerstones of current immunosuppressive regimens. However, they are also the main culprits of adverse-events and side-effects encountered after transplantation. Lowering the doses of each drug, or even eliminating them from the immunosuppressive menu, has been evaluated by many groups over the last two decades. This review summarises a huge number of studies dealing with corticosteroid and calcineurin inhibitor minimization, including withdrawal and avoidance trials. It is hard today to propose any practical guidelines on such a controversial topic. Good results are achieved by some groups and bad results by others. The lack of long-term follow-up in randomized studies contributes to this debate. Nevertheless, it seems possible and safe to avoid corticosteroids and/or calcineurin inhibitors in many patients. The application of protocol biopsies as well as new immunological tests to determine the degree of immunosuppression will certainly help transplant physicians to provide more personalized treatment strategies

Posttransplant Donor-Specific Anti-HLA Antibodies Negatively Impact Pancreas Transplantation Outcome

During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreaskidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donorspecific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p < 0.05) or to negative patients (p <0.001). Contrastingwith the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failureswere significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p < 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients