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.

Keywords: Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Follow-Up Studies; Graft Survival; Humans; Immunosuppression; Immunosuppressive Agents; Mycophenolic Acid; Tissue Donors; kidney transplantation; rejection; tacrolimus.

Figure 1.

Number of kidney transplants performed in the United States on the basis of induction type and transplant year among deceased donor renal transplantation recipients maintained on tacrolimus/mycophenolic acid at transplantation hospital discharge. IL2-RA, IL-2 receptor antagonist; r-ATG, rabbit antithymocyte globulin.

Figure 2.

Incidence of acute rejection at 1 year (percentage) among deceased donor renal transplantation recipients maintained on tacrolimus/mycophenolic acid at transplantation hospital discharge on the basis of induction type and transplant year in the United States. IL2-RA, IL-2 receptor antagonist; r-ATG, rabbit antithymocyte globulin.

Figure 3.

Unweighted Kaplan–Meier overall graft survival estimates in deceased donor renal transplantation (DDRT) recipients maintained on tacrolimus (TAC)/mycophenolic acid (MPA)/steroids by induction types. (A) Steroid group. (B) No-steroid group. IL2-RA, IL-2 receptor antagonist; r-ATG, rabbit antithymocyte globulin.

Figure 4.

Comparison of the estimated association of induction treatments on acute rejection within one-year and overall graft failure (IL-2 receptor antagonist [IL2-RA] is the referent category in all models). (A) Acute rejection within one-year using propensity score (PS) weighted multivariable logistic regression models in the steroid group. (B) Overall graft failure using PS weighted multivariable Cox regression models in the steroid group. (C) Acute rejection within one-year using PS weighted multivariable logistic regression models in the no-steroid group. (D) overall graft failure using PS weighted multivariable Cox regression models in the no-steroid group. 95% CI, 95% confidence interval; AA, black; CIT, cold ischemia time; OR, odds ratio; KDPI, kidney donor profile index; PRA, panel reactive antibody; r-ATG, rabbit antithymocyte globulin; Re-Txp, re-transplant.

Figure 4.

Comparison of the estimated association of induction treatments on acute rejection within one-year and overall graft failure (IL-2 receptor antagonist [IL2-RA] is the referent category in all models). (A) Acute rejection within one-year using propensity score (PS) weighted multivariable logistic regression models in the steroid group. (B) Overall graft failure using PS weighted multivariable Cox regression models in the steroid group. (C) Acute rejection within one-year using PS weighted multivariable logistic regression models in the no-steroid group. (D) overall graft failure using PS weighted multivariable Cox regression models in the no-steroid group. 95% CI, 95% confidence interval; AA, black; CIT, cold ischemia time; OR, odds ratio; KDPI, kidney donor profile index; PRA, panel reactive antibody; r-ATG, rabbit antithymocyte globulin; Re-Txp, re-transplant.

Figure 4.

Comparison of the estimated association of induction treatments on acute rejection within one-year and overall graft failure (IL-2 receptor antagonist [IL2-RA] is the referent category in all models). (A) Acute rejection within one-year using propensity score (PS) weighted multivariable logistic regression models in the steroid group. (B) Overall graft failure using PS weighted multivariable Cox regression models in the steroid group. (C) Acute rejection within one-year using PS weighted multivariable logistic regression models in the no-steroid group. (D) overall graft failure using PS weighted multivariable Cox regression models in the no-steroid group. 95% CI, 95% confidence interval; AA, black; CIT, cold ischemia time; OR, odds ratio; KDPI, kidney donor profile index; PRA, panel reactive antibody; r-ATG, rabbit antithymocyte globulin; Re-Txp, re-transplant.