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

Abstract

Background and objectives 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.Design, setting, participants, & measurements 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.Results 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).Conclusions 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.

Effect of Interleukin-2 Receptor Antibody Induction Therapy on Survival in Renal Transplant Patients Receiving Tacrolimus

“…The results of our study agreed with the results of other large registry data studies in the United States and Australia that tried to assess same questions. Using organ procurement and transplantation network data, Tanriover et al [11,12] found no significant difference between the IL2-RA induction and the no-induction group in terms of patient or graft survival among renal transplant recipients from live and deceased transplant donors. Both studies included a large sample size and had adequate follow-up time up to 5 years post-transplant.…”

“…The study population were restricted to standard risk patients who were maintained on tacrolimus-based immunotherapy. Standard risk transplants were defined as patients with < 2DR mismatch, calculated reaction frequency (CRF) < 20%, live donors or donors after brain death and patients with no previous renal transplantation [8,[10][11][12][13]. CRF is an indication of the level of sensitization and reflects the percentage of blood group identical, HLA incompatible donors [14].…”

Identification of expanded T-cell clones by spectratyping in nonfunctioning kidney transplants

“…The introduction of new immunosuppressant drugs has greatly decreased the number and impact of acute rejections, which however is still a critical complication 3,4. Unfortunately, several pathological changes due to immunological and nonimmunological components for organ loss lead to a progressive loss of graft function, and this condition does not seem to have received consistent benefits from the new pharmacological treatments 5,6.…”

Very early acute rejection in an Australian and New Zealand kidney transplant population

“…Acute rejection remains an important and common complication of this treatment despite a decrease in incidence from 60% in the early 1980s to as low as 10% in present day due to advances in medical, surgical and immunological management (1). Quoted rates vary with immunosuppression regime and the alloimmune risk of studied populations (2)(3)(4).…”

“…Consequences of acute rejection include graft dysfunction and late graft loss (5)(6)(7). Although acute rejection has been identified as a strong predictor of graft loss, the worldwide attrition in acute rejection rate is no longer mirrored to the same extent by changes in graft survival (4,8).…”