Induction Therapies in Live Donor Kidney Transplantation on Tacrolimus and Mycophenolate With or Without Steroid Maintenance.

Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first line agent in living donor renal transplantation (LRT). However, use of IL2-RA remains controversial in LRT with tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. The Organ Procurement and Transplantation Network registry was studied for patients receiving LRT from 2000 to 2012 maintained on TAC/MPA at discharge (n=36,153) to compare effectiveness of IL2-RA to other induction options. The cohort was initially divided into two groups based on use of maintenance steroid at time of hospital discharge: steroid (n=25,996) versus no-steroid (n=10,157). Each group was further stratified into three categories according to commonly used antibody induction approach: IL2-RA, rabbit anti-thymocyte globulin (r-ATG), and no-induction in the steroid group versus IL2-RA, r-ATG and alemtuzumab in the no-steroid group. The main outcomes were the risk of acute rejection at 1 year and overall allograft failure (graft failure or death) post-transplantation through the end of follow-up. Propensity score-weighted regression analysis was used to minimize selection bias due to non-random assignment of induction therapies. Multivariable logistic and Cox analysis adjusted for propensity score showed that outcomes in the steroid group were similar between no-induction (odds ratio [OR], 0.96; 95% confidence interval [95% CI], 0.86 to 1.08 for acute rejection; and hazard ratio [HR], 0.99; 95% CI, 0.90 to 1.08 for overall allograft failure) and IL2-RA categories. In the no-steroid group, odds of acute rejection with r-ATG (OR, 0.73; 95% CI, 0.59 to 0.90) and alemtuzumab (OR, 0.53; 95% CI, 0.42 to 0.67) were lower; however, overall allograft failure risk was higher with alemtuzumab (HR, 1.27; 95% CI, 1.03 to 1.56) but not with r-ATG (HR, 1.19; 95% CI, 0.97 to 1.45), compared with IL2-RA induction. Compared with no-induction therapy, IL2-RA induction was not associated with better outcomes when TAC/MPA/steroids were used in LRT recipients. r-ATG appears to be an acceptable and possibly the preferred induction alternative for IL2-RA in steroid-avoidance protocols.

Tanriover B ，Zhang S ，MacConmara M ，Gao A ，Sandikci B ，Ayvaci MU ，Mete M ，Tsapepas D ，Rajora N ，Mohan P ，Lakhia R ，Lu CY ，Vazquez M ... -  《-》

Acute Rejection Rates and Graft Outcomes According to Induction Regimen among Recipients of Kidneys from Deceased Donors Treated with Tacrolimus and Mycophenolate.

IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent for induction therapy in renal transplantation. However, this remains controversial in deceased donor renal transplantation (DDRT) maintained on tacrolimus (TAC)/mycophenolic acid (MPA) with or without steroids. We studied the United Network for Organ Sharing Registry for patients receiving DDRT from 2000 to 2012 maintained on TAC/MPA at transplantation hospital discharge (n=74,627) to compare outcomes of IL2-RA and other induction agents. We initially divided the cohort into two groups on the basis of steroid use at the time of discharge: steroid (n=59,010) versus no steroid (n=15,617). Each group was stratified into induction categories: IL2-RA, rabbit antithymocyte globulin (r-ATG), alemtuzumab, and no induction. The main outcomes were incidence of acute rejection within the first year and overall graft failure (defined as graft failure and/or death) post-transplantation. Propensity score (PS), specifically inverse probability of treatment weight, analysis was used to minimize selection bias caused by nonrandom assignment of induction therapies. Median (25th, 75th percentiles) follow-up times were 3.9 (1.1, 5.9) and 3.2 (1.1, 4.9) years for steroid and no steroid groups, respectively. Acute rejection within the first year and overall graft failure within 5 years of transplantation were more common in the no induction category (13.3%; P<0.001 and 28%; P=0.01, respectively) in the steroid group and the IL2-RA category (11.1%; P=0.16 and 27.4%; P<0.001, respectively) in the no steroid group. Compared with IL2-RA, PS-weighted and covariate-adjusted multivariable logistic and Cox analyses showed that outcomes in the steroid group were similar among induction categories, except that acute rejection was significantly lower with r-ATG (odds ratio [OR], 0.68; 95% confidence interval [95% CI], 0.62 to 0.74). In the no steroid group, compared with IL2-RA, odds of acute rejection with r-ATG (OR, 0.80; 95% CI, 0.60 to 1.00) and alemtuzumab (OR, 0.68; 95% CI, 0.53 to 0.88) were lower, and r-ATG was associated with better graft survival (hazard ratio, 0.86; 95% CI, 0.75 to 0.99). In DDRT, compared with IL2-RA induction, no induction was associated with similar outcomes when TAC/MPA/steroids were used. r-ATG seems to offer better graft survival over IL2-RA in steroid avoidance protocols.

Tanriover B ，Jaikaransingh V ，MacConmara MP ，Parekh JR ，Levea SL ，Ariyamuthu VK ，Zhang S ，Gao A ，Ayvaci MUS ，Sandikci B ，Rajora N ，Ahmed V ，Lu CY ，Mohan S ，Vazquez MA ... -  《-》

Influence of induction modality on the outcome of deceased donor kidney transplant recipients discharged on steroid-free maintenance immunosuppression.

Sureshkumar KK ，Thai NL ，Hussain SM ，Ko TY ，Marcus RJ ... -  《-》

Polyclonal and monoclonal antibodies for induction therapy in kidney transplant recipients.

Hill P ，Cross NB ，Barnett AN ，Palmer SC ，Webster AC ... -  《Cochrane Database of Systematic Reviews》

Influence of maintenance steroids on the outcomes in deceased-donor kidney transplant recipients exposed to prolonged pretransplantation dialysis.

Pre-transplant dialysis duration exerts a graded negative influence on outcomes after kidney transplantation. Higher immune reactivity associated with prolonged dialysis with consequent increased acute rejection could be contributory. Using the Organ Procurement and Transplant Network/United Network of Organ Sharing database, we identified patients ≥ 18 years of age who received deceased-donor kidney (DDK) transplants from 2000 to 2008 after being on maintenance dialysis for ≥ 4 years. Patients received induction therapy with rabbit antithymocyte globulin (r-ATG), alemtuzumab, or an interleukin-2 receptor blocker (IL-2B) and were discharged on calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)-based immunosuppression with or without steroid. Unadjusted and adjusted graft/patient survivals were compared in steroid versus no-steroid groups by induction type. A total of 14,459 patients were identified, of which 7,684 received r-ATG (steroid, 6,098; no-steroid, 1,586), 1,292 alemtuzumab (steroid, 362; no-steroid, 930), and 5,483 an IL-2B agent (steroid, 5,107; no-steroid, 376). Adjusted graft survivals were similar for steroid versus no-steroid groups in r-ATG (hazard ratio [HR] 1.10, 95% confidence interval (CI) 0.96-1.26, P = .16), alemtuzumab (HR 0.88, 95% CI 0.65-1.19; P = .40), and IL-2B (HR 0.91, 95% CI 0.73-1.13; P = .38) groups. Adjusted patient survival for steroid versus no-steroid groups was inferior in r-ATG (HR 1.41, 95% CI 1.17-1.71; P < .001) but similar in alemtuzumab (HR 1.05, 95% CI 0.70-1.59; P = .80) and IL-2B (HR 1.17, 95% CI 0.86-1.58; P = .32) groups. Our analysis failed to show a graft survival benefit for the addition of steroid to a CNI/MMF-based immunosuppression after induction with r-ATG, alemtuzumab, or an IL-2B agent in DDK recipients exposed to prolonged pretransplantation dialysis.

Sureshkumar KK ，Hussain SM ，Thai NL ，Marcus RJ ... -  《-》