Long-term outcomes after acute rejection in kidney transplant recipients: An ANZDATA analysis

Philip A Clayton, Stephen P McDonald, Graeme R Russ, Steven J Chadban

Research output: Contribution to journalArticle

Abstract

Background Declining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients. Methods To understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics. Results AR occurred in 2906 recipients (21.4%) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95% CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95% CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95% CI, 1.11 to 1.53) and cancer (HR, 1.35; 95% CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results. Conclusions AR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.

LanguageEnglish
Pages1697-1707
Number of pages11
JournalJournal of the American Society of Nephrology
Volume30
Issue number9
Early online date15 Jul 2019
DOIs
Publication statusPublished - 1 Sep 2019

ASJC Scopus subject areas

  • Nephrology

Cite this

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title = "Long-term outcomes after acute rejection in kidney transplant recipients: An ANZDATA analysis",
abstract = "Background Declining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients. Methods To understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics. Results AR occurred in 2906 recipients (21.4{\%}) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95{\%} confidence interval [95{\%} CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95{\%} CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95{\%} CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95{\%} CI, 1.11 to 1.53) and cancer (HR, 1.35; 95{\%} CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results. Conclusions AR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.",
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Long-term outcomes after acute rejection in kidney transplant recipients : An ANZDATA analysis. / Clayton, Philip A; McDonald, Stephen P; Russ, Graeme R; Chadban, Steven J.

In: Journal of the American Society of Nephrology, Vol. 30, No. 9, 01.09.2019, p. 1697-1707.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Long-term outcomes after acute rejection in kidney transplant recipients

T2 - Journal of the American Society of Nephrology

AU - Clayton, Philip A

AU - McDonald, Stephen P

AU - Russ, Graeme R

AU - Chadban, Steven J

N1 - Copyright © 2019 by the American Society of Nephrology.

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Background Declining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients. Methods To understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics. Results AR occurred in 2906 recipients (21.4%) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95% CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95% CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95% CI, 1.11 to 1.53) and cancer (HR, 1.35; 95% CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results. Conclusions AR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.

AB - Background Declining rates of acute rejection (AR) and the high rate of 1-year graft survival among patients with AR have prompted re-examination of AR as an outcome in the clinic and in trials. Yet AR and its treatment may directly or indirectly affect longer-term outcomes for kidney transplant recipients. Methods To understand the long-term effect of AR on outcomes, we analyzed data from the Australia and New Zealand Dialysis and Transplant Registry, including 13,614 recipients of a primary kidney-only transplant between 1997 and 2017 with at least 6 months of graft function. The associations between AR within 6 months post-transplant and subsequent cause-specific graft loss and death were determined using Cox models adjusted for baseline donor, recipient, and transplant characteristics. Results AR occurred in 2906 recipients (21.4%) and was associated with graft loss attributed to chronic allograft nephropathy (hazard ratio [HR], 1.39; 95% confidence interval [95% CI], 1.23 to 1.56) and recurrent AR beyond month 6 (HR, 1.85; 95% CI, 1.39 to 2.46). Early AR was also associated with death with a functioning graft (HR, 1.22; 95% CI, 1.08 to 1.36), and with death due to cardiovascular disease (HR, 1.30; 95% CI, 1.11 to 1.53) and cancer (HR, 1.35; 95% CI, 1.12 to 1.64). Sensitivity analyses restricted to subgroups with either biopsy-proven, antibody-mediated, or vascular rejection, or stratified by treatment response produced similar results. Conclusions AR is associated with increased risks of longer-term graft failure and death, particularly death from cardiovascular disease and cancer. The results suggest AR remains an important short-term outcome to monitor in kidney transplantation and clinical trials.

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U2 - 10.1681/ASN.2018111101

DO - 10.1681/ASN.2018111101

M3 - Article

VL - 30

SP - 1697

EP - 1707

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 9

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