Acute rejection rates and graft outcomes according to induction regimen among recipients of kidneys from deceased donors treated with tacrolimus and mycophenolate

Bekir Tanriover*, Vishal Jaikaransingh, Malcolm P. MacConmara, Justin R. Parekh, Swee Ling Levea, Venkatesh K. Ariyamuthu, Song Zhang, Ang Gao, Mehmet U.S. Ayvaci, Burhaneddin Sandikci, Nilum Rajora, Vaqar Ahmed, Christopher Y. Lu, Sumit Mohan, Miguel A. Vazquez

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

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. 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.

Original languageEnglish
Pages (from-to)1650-1661
Number of pages12
JournalClinical journal of the American Society of Nephrology : CJASN
Volume11
Issue number9
DOIs
Publication statusPublished - 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 by the American Society of Nephrology.

Funding

On the basis of the Organ Procurement and Transplantation Network data as of September 30, 2013, this workwas supported, in part, by Health Resources and Services Administration contract 234-2005-370011C. This research is partly supported by University of Texas Southwestern O’Brien Kidney Research Core Center grant P30DK079328. The content is the responsibility of the authors alone and does not necessarily reflect the views or policies of the Department of Health and Human Services, and the mention of trade names, commercial products, or organizations does not imply endorsement by the US Government.

FundersFunder number
University of Texas Southwestern O’Brien Kidney Research Core Center
U.S. Department of Health and Human Services
National Institute of Diabetes and Digestive and Kidney DiseasesP30DK079328
Health Resources and Services Administration234-2005-370011C
Government of South Australia

    Keywords

    • Antibodies, Monoclonal, Humanized
    • Antilymphocyte Serum
    • Follow-Up Studies
    • Graft Survival
    • Humans
    • Immunosuppression
    • Immunosuppressive Agents
    • Kidney transplantation
    • Mycophenolic Acid
    • Rejection
    • Tacrolimus
    • Tissue Donors

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