TY - JOUR
T1 - Acute rejection rates and graft outcomes according to induction regimen among recipients of kidneys from deceased donors treated with tacrolimus and mycophenolate
AU - Tanriover, Bekir
AU - Jaikaransingh, Vishal
AU - MacConmara, Malcolm P.
AU - Parekh, Justin R.
AU - Levea, Swee Ling
AU - Ariyamuthu, Venkatesh K.
AU - Zhang, Song
AU - Gao, Ang
AU - Ayvaci, Mehmet U.S.
AU - Sandikci, Burhaneddin
AU - Rajora, Nilum
AU - Ahmed, Vaqar
AU - Lu, Christopher Y.
AU - Mohan, Sumit
AU - Vazquez, Miguel A.
N1 - Publisher Copyright:
© 2016 by the American Society of Nephrology.
PY - 2016
Y1 - 2016
N2 - 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. ResultsMedian (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 transplantationweremore 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.
AB - 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. ResultsMedian (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 transplantationweremore 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.
KW - Antibodies, Monoclonal, Humanized
KW - Antilymphocyte Serum
KW - Follow-Up Studies
KW - Graft Survival
KW - Humans
KW - Immunosuppression
KW - Immunosuppressive Agents
KW - Kidney transplantation
KW - Mycophenolic Acid
KW - Rejection
KW - Tacrolimus
KW - Tissue Donors
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U2 - 10.2215/CJN.13171215
DO - 10.2215/CJN.13171215
M3 - Article
C2 - 27364616
AN - SCOPUS:85012953560
SN - 1555-9041
VL - 11
SP - 1650
EP - 1661
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 9
ER -