Kidney transplantation in sensitized patients

Sensitization is defi ned as the presence of preformed alloantibodies in the
serum prior to transplantation. Highly sensitized patients present limited
access to organs and increased risk of acute humoral rejection. Aspects of
immunosuppression of highly sensitized kidney transplant patients include
desensitization therapy prior to transplantation, induction therapy with transplantation, maintenance therapy after transplantation and rescue therapy of acute humoral rejection. The aim of this multicenter, randomized study was to determine efficacious and safe immunosuppressive regimen in renal transplant recipients. Sixty two (30 males) sensitized cadaveric renal transplant recipients, aged 15-55 years, were included in the study and followed-up for 36 months. High immunologic risk was defined as retransplantation (2[sup]nd[/sup] [n=34] or 3[sup]rd[/sup][n=l graft) in pts with history of immunologic complications or PRA >25%. PRA range was 0-24% (n=28), 25-36% (n=23), and >36% (n=11). HLA mismatches (MM) in class I (A + B) were 16.1, 26, 35.5, 11.4, and 4.8%, for 4, 3, 2, 1 and 0 MM, respectively and in class II (DR) were 14.5, 5, and 26% for 2, 1 and 0 MM, respectively. Pts were randomized to receive ATG (3 mg/kg; 4 doses) + Steroids + Tacrolimus (Tac) and either mycophenolate mofetil (MMF) (n=40) or Sirolimus (Sir) (n=22). 1-year graft and patient survival were estimated with Kaplan-Meier method. Renal function (expressed as estimated GFR [eGFR calculated by MDRD formula] was monitored for 24 months. Renal function was stable in both MMF and Sir groups, with eGFR slope significantly more positive in MMF group over 2 years after transplantation (p<0.045). Delayed graft function was observed in 35.5% pts. In 39% pts biopsy-proven acute rejection episodes were diagnosed (early [up to month 3] in 17%, late in 20%), in 32.5% pts on MMF, and in 45.5% on Sir. Significantly higher cholesterol and trigliceryde levels, and lower hemoglobin and hematocrit were observed in Sir group. 8 kidney grafts were lost during follow-up 5 and 3 in MMF and Sir groups, respectively. 4 patients were converted from Rapa to MMF due to thrombotic microangiopathy, 2 patients from MMF to Sir due to neoplasia. Serious complications were comparable in both groups (1 pts died [brain abscess], 1 nephrectomy [renal cell carcinoma], l pulmonary aspergillosis). MMF-based immunosuppressive regimen proved more safe and efficacious than sirolimus-based therapy in high immunologic risk kidney transplantation, resulting in better graft function and lower incidence of adverse effects. Kaplan-Meier estimates of l-year patient and graft survival showed a trend in benefit of MMF.

Keywords: Kidney Transplantation