Introduction
Transplant results are less successful when donors and recipients are HLA incompatible. Histocompatibility labs evaluate immunological risk primarily through serologic and cell-based testing. HLA-incompatible transplants have been defined in several ways in the transplantation literature. It is crucial to evaluate the prognostic significance of HLA incompatibility to kidney transplant outcomes in order to compare immunological risk across molecular, serologic, and cell-based approaches. HLA incompatibility-based transplant results depend on demographic traits, the clinical environment, and the immune-modulatory treatments used during the entire posttransplant course. When planning investigations and conducting data analysis, it’s crucial to take their modifying impacts into account. This systematic review aimed to determine the extent to which a predefined set of HLA incompatibility-related characteristics were mentioned in recent peer-reviewed literature. Additionally, we identified variables that might account for variations between included studies, evaluated the quality of the evidence, and did a narrative synthesis to summarise the direction and amount of the estimated effects of each definition of HLA incompatibility on 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. The Preferred Reporting Items for Systematic reviews and Meta-Analyses diagram outlining the article selection process is provided in Figure 1.
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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