Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies: a systematic review

Ankit Sharma, Joshua R. Lewis, Wai H. Lim, Suetonia Palmer, Giovanni Strippoli, Jeremy R. Chapman, Stephen I. Alexander, Jonathan C. Craig, Germaine Wong

Research output: Contribution to journalReview article

5 Citations (Scopus)

Abstract

Background. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain.

Methods. We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available.

Results. Thirty-six studies involving 10 535 transplant recipients were eligible. There was moderate quality evidence that transplant recipients who developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR) [relative risk (RR) 9.66; 95% confidence interval (CI) 6.79-13.73, 16 studies, n = 4174]. For all other outcomes, the evidence was low to very low due to moderate-high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95% CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and transplant glomerulopathy RR 6.78; 95% CI 4.31-10.66, 3 studies, n = 1617, very low-quality evidence; and graft loss RR 4.95; 95% CI 3.81-6.43, 19 studies, n = 5473, low-quality evidence). Meta-regression indicated that deceased kidney donation (R-2 = 1.00, P <0.001) and region of study conduction (R-2 = 0.50, P = 0.005) modified associations between dnDSAs and outcomes.

Conclusions. dnDSAs are associated with increased risks of adverse graft and patient outcomes after kidney transplantation, but estimation uncertainty of the augmented risks exist due to limitations such as heterogeneity within the existing literature. Therapeutic interventions targeted to eliminate or prevent these antibodies evaluated in randomized controlled trials are needed to establish whether dnDSAs are causal to transplantation outcomes.

Original languageEnglish
Pages (from-to)1472-1480
Number of pages10
JournalNephrology Dialysis Transplantation
Volume33
Issue number8
DOIs
Publication statusPublished - Aug 2018

Cite this

Sharma, Ankit ; Lewis, Joshua R. ; Lim, Wai H. ; Palmer, Suetonia ; Strippoli, Giovanni ; Chapman, Jeremy R. ; Alexander, Stephen I. ; Craig, Jonathan C. ; Wong, Germaine. / Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies : a systematic review. In: Nephrology Dialysis Transplantation. 2018 ; Vol. 33, No. 8. pp. 1472-1480.
@article{bd2d1ff0e332404a998ef6c2b62b417b,
title = "Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies: a systematic review",
abstract = "Background. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain.Methods. We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available.Results. Thirty-six studies involving 10 535 transplant recipients were eligible. There was moderate quality evidence that transplant recipients who developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR) [relative risk (RR) 9.66; 95{\%} confidence interval (CI) 6.79-13.73, 16 studies, n = 4174]. For all other outcomes, the evidence was low to very low due to moderate-high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95{\%} CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and transplant glomerulopathy RR 6.78; 95{\%} CI 4.31-10.66, 3 studies, n = 1617, very low-quality evidence; and graft loss RR 4.95; 95{\%} CI 3.81-6.43, 19 studies, n = 5473, low-quality evidence). Meta-regression indicated that deceased kidney donation (R-2 = 1.00, P <0.001) and region of study conduction (R-2 = 0.50, P = 0.005) modified associations between dnDSAs and outcomes.Conclusions. dnDSAs are associated with increased risks of adverse graft and patient outcomes after kidney transplantation, but estimation uncertainty of the augmented risks exist due to limitations such as heterogeneity within the existing literature. Therapeutic interventions targeted to eliminate or prevent these antibodies evaluated in randomized controlled trials are needed to establish whether dnDSAs are causal to transplantation outcomes.",
keywords = "antibody-mediated rejection, donor-specific antibodies, graft outcomes, meta-analysis, systematic review, KIDNEY ALLOGRAFT RECIPIENTS, HLA ANTIBODIES, MEDIATED REJECTION, IMPROVE OUTCOMES, METAANALYSIS, EPITOPES, STRATEGY, THERAPY, FAILURE, RISK",
author = "Ankit Sharma and Lewis, {Joshua R.} and Lim, {Wai H.} and Suetonia Palmer and Giovanni Strippoli and Chapman, {Jeremy R.} and Alexander, {Stephen I.} and Craig, {Jonathan C.} and Germaine Wong",
year = "2018",
month = "8",
doi = "10.1093/ndt/gfy077",
language = "English",
volume = "33",
pages = "1472--1480",
journal = "Nephrology, Dialysis, Transplantation",
issn = "0931-0509",
publisher = "OXFORD UNIV PRESS UNITED KINGDOM",
number = "8",

}

Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies : a systematic review. / Sharma, Ankit; Lewis, Joshua R.; Lim, Wai H.; Palmer, Suetonia; Strippoli, Giovanni; Chapman, Jeremy R.; Alexander, Stephen I.; Craig, Jonathan C.; Wong, Germaine.

In: Nephrology Dialysis Transplantation, Vol. 33, No. 8, 08.2018, p. 1472-1480.

Research output: Contribution to journalReview article

TY - JOUR

T1 - Renal transplant outcomes and de novo donor-specific anti-human leukocyte antigen antibodies

T2 - a systematic review

AU - Sharma, Ankit

AU - Lewis, Joshua R.

AU - Lim, Wai H.

AU - Palmer, Suetonia

AU - Strippoli, Giovanni

AU - Chapman, Jeremy R.

AU - Alexander, Stephen I.

AU - Craig, Jonathan C.

AU - Wong, Germaine

PY - 2018/8

Y1 - 2018/8

N2 - Background. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain.Methods. We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available.Results. Thirty-six studies involving 10 535 transplant recipients were eligible. There was moderate quality evidence that transplant recipients who developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR) [relative risk (RR) 9.66; 95% confidence interval (CI) 6.79-13.73, 16 studies, n = 4174]. For all other outcomes, the evidence was low to very low due to moderate-high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95% CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and transplant glomerulopathy RR 6.78; 95% CI 4.31-10.66, 3 studies, n = 1617, very low-quality evidence; and graft loss RR 4.95; 95% CI 3.81-6.43, 19 studies, n = 5473, low-quality evidence). Meta-regression indicated that deceased kidney donation (R-2 = 1.00, P <0.001) and region of study conduction (R-2 = 0.50, P = 0.005) modified associations between dnDSAs and outcomes.Conclusions. dnDSAs are associated with increased risks of adverse graft and patient outcomes after kidney transplantation, but estimation uncertainty of the augmented risks exist due to limitations such as heterogeneity within the existing literature. Therapeutic interventions targeted to eliminate or prevent these antibodies evaluated in randomized controlled trials are needed to establish whether dnDSAs are causal to transplantation outcomes.

AB - Background. Pre-transplant donor-specific anti-human leukocyte antigen antibodies (DSAs) are known risk factors for acute rejection and reduced graft survival after kidney transplantation. DSAs may also develop de novo DSAs (dnDSAs) after transplantation but the clinical implications of these antibodies remain uncertain.Methods. We undertook a systematic review of observational studies that examined the association between dnDSAs and graft and patient outcomes (through August 2017) with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system of reporting used to assess the quality of evidence available.Results. Thirty-six studies involving 10 535 transplant recipients were eligible. There was moderate quality evidence that transplant recipients who developed dnDSAs had increased risks of acute antibody-mediated rejection (AMR) [relative risk (RR) 9.66; 95% confidence interval (CI) 6.79-13.73, 16 studies, n = 4174]. For all other outcomes, the evidence was low to very low due to moderate-high heterogeneity and low study quality (acute cellular rejection, RR 2.92; 95% CI 2.16-3.94, 22 studies, n = 4991, low-quality evidence; chronic AMR and transplant glomerulopathy RR 6.78; 95% CI 4.31-10.66, 3 studies, n = 1617, very low-quality evidence; and graft loss RR 4.95; 95% CI 3.81-6.43, 19 studies, n = 5473, low-quality evidence). Meta-regression indicated that deceased kidney donation (R-2 = 1.00, P <0.001) and region of study conduction (R-2 = 0.50, P = 0.005) modified associations between dnDSAs and outcomes.Conclusions. dnDSAs are associated with increased risks of adverse graft and patient outcomes after kidney transplantation, but estimation uncertainty of the augmented risks exist due to limitations such as heterogeneity within the existing literature. Therapeutic interventions targeted to eliminate or prevent these antibodies evaluated in randomized controlled trials are needed to establish whether dnDSAs are causal to transplantation outcomes.

KW - antibody-mediated rejection

KW - donor-specific antibodies

KW - graft outcomes

KW - meta-analysis

KW - systematic review

KW - KIDNEY ALLOGRAFT RECIPIENTS

KW - HLA ANTIBODIES

KW - MEDIATED REJECTION

KW - IMPROVE OUTCOMES

KW - METAANALYSIS

KW - EPITOPES

KW - STRATEGY

KW - THERAPY

KW - FAILURE

KW - RISK

U2 - 10.1093/ndt/gfy077

DO - 10.1093/ndt/gfy077

M3 - Review article

VL - 33

SP - 1472

EP - 1480

JO - Nephrology, Dialysis, Transplantation

JF - Nephrology, Dialysis, Transplantation

SN - 0931-0509

IS - 8

ER -