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

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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 (US)
Pages (from-to)1650-1661
Number of pages12
JournalClinical Journal of the American Society of Nephrology
Volume11
Issue number9
DOIs
StatePublished - 2016

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Graft Rejection
Tacrolimus
Steroids
Tissue Donors
Kidney
Interleukin-2
Antilymphocyte Serum
Mycophenolic Acid
Kidney Transplantation
Rabbits
Confidence Intervals
Propensity Score
Odds Ratio
Graft Survival
Transplants
Transplantation
Selection Bias
Interleukin-2 Receptors
Registries
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

Cite this

@article{fc6e23584e114999bffc5f3e62edf381,
title = "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. 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.",
keywords = "Antibodies, Monoclonal, Humanized, Antilymphocyte Serum, Follow-Up Studies, Graft Survival, Humans, Immunosuppression, Immunosuppressive Agents, Kidney transplantation, Mycophenolic Acid, Rejection, Tacrolimus, Tissue Donors",
author = "Bekir Tanriover and Vishal Jaikaransingh and MacConmara, {Malcolm P.} and Parekh, {Justin R.} and Levea, {Swee Ling} and Ariyamuthu, {Venkatesh K.} and Song Zhang and Ang Gao and Ayvaci, {Mehmet U.S.} and Burhaneddin Sandikci and Nilum Rajora and Vaqar Ahmed and Lu, {Christopher Y.} and Sumit Mohan and Vazquez, {Miguel A.}",
year = "2016",
doi = "10.2215/CJN.13171215",
language = "English (US)",
volume = "11",
pages = "1650--1661",
journal = "Clinical Journal of the American Society of Nephrology",
issn = "1555-9041",
publisher = "American Society of Nephrology",
number = "9",

}

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.

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

VL - 11

SP - 1650

EP - 1661

JO - Clinical Journal of the American Society of Nephrology

JF - Clinical Journal of the American Society of Nephrology

SN - 1555-9041

IS - 9

ER -