TY - JOUR
T1 - Seeking Standardized Definitions for HLA-incompatible Kidney Transplants
T2 - A Systematic Review
AU - Jatana, Sukhdeep S.
AU - Zhao, Hedi
AU - Bow, Laurine M.
AU - Cozzi, Emanuele
AU - Batal, Ibrahim
AU - Horak, Tillie
AU - Amar-Zifkin, Alexandre
AU - Schinstock, Carrie
AU - Askar, Medhat
AU - Dadhania, Darshana M.
AU - Cooper, Matthew
AU - Naesens, Maarten
AU - Kraus, Edward S.
AU - Sapir-Pichhadze, Ruth
N1 - Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background. There is no standard definition for "HLA incompatible" transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes. Methods. We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility. Results. Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains. Conclusions. Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
AB - Background. There is no standard definition for "HLA incompatible" transplants. For the first time, we systematically assessed how HLA incompatibility was defined in contemporary peer-reviewed publications and its prognostic implication to transplant outcomes. Methods. We combined 2 independent searches of MEDLINE, EMBASE, and the Cochrane Library from 2015 to 2019. Content-expert reviewers screened for original research on outcomes of HLA-incompatible transplants (defined as allele or molecular mismatch and solid-phase or cell-based assays). We ascertained the completeness of reporting on a predefined set of variables assessing HLA incompatibility, therapies, and outcomes. Given significant heterogeneity, we conducted narrative synthesis and assessed risk of bias in studies examining the association between death-censored graft failure and HLA incompatibility. Results. Of 6656 screened articles, 163 evaluated transplant outcomes by HLA incompatibility. Most articles reported on cytotoxic/flow T-cell crossmatches (n = 98). Molecular genotypes were reported for selected loci at the allele-group level. Sixteen articles reported on epitope compatibility. Pretransplant donor-specific HLA antibodies were often considered (n = 143); yet there was heterogeneity in sample handling, assay procedure, and incomplete reporting on donor-specific HLA antibodies assignment. Induction (n = 129) and maintenance immunosuppression (n = 140) were frequently mentioned but less so rejection treatment (n = 72) and desensitization (n = 70). Studies assessing death-censored graft failure risk by HLA incompatibility were vulnerable to bias in the participant, predictor, and analysis domains. Conclusions. Optimization of transplant outcomes and personalized care depends on accurate HLA compatibility assessment. Reporting on a standard set of variables will help assess generalizability of research, allow knowledge synthesis, and facilitate international collaboration in clinical trials.
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U2 - 10.1097/TP.0000000000004262
DO - 10.1097/TP.0000000000004262
M3 - Article
C2 - 35915547
AN - SCOPUS:85144094028
SN - 0041-1337
VL - 107
SP - 231
EP - 253
JO - Transplantation
JF - Transplantation
IS - 1
ER -