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Objective: Angiotensin II type-1 receptor antibodies (AT1R-Ab) and endothelin-1 type-A receptor antibodies (ETAR-Ab) are non-human leukocyte antigen (HLA) antibodies that can elicit adverse effects on kidney transplantation (KT) outcomes. We investigated the correlation between levels of AT1R-Ab and ETAR-Ab and postoperative outcomes in KT recipients. Methods: Pre-KT and post-KT serum from 79 patients was collected. Post-KT serum was collected within 1 year after KT or simultaneously as the biopsy. Levels of AT1R-Ab and ETAR-Ab were measured using enzyme-linked immunosorbent assay kits. AT1R-Ab >17.0 U/mL and ETAR-Ab >10.0 U/mL was considered to denote positivity according to manufacturer recommendations. We measured donor-specific antibodies against human leukocyte antigens (HLA-DSA) levels using LABScreen™ single-antigen kits. Results: Seventy-nine (54 men, 25 women) formed the study cohort. Seven (8.7%) patients were positive for AT1R-Ab, 25 (31.6%) patients were positive for both AT1R-Ab and ETAR-Ab, and 47 (59.5%) were negative for both antibodies at all time points. No patients died during the study period. Patients with both AT1R-Ab and ETAR-Ab were associated with a higher prevalence of antibody-mediated rejection (AMR) and lower estimated glomerular filtration rate, but not allograft loss or delayed graft function. AT1R-Ab were associated with T-cell-mediated rejection, but the association was not significant. HLA-DSA were associated significantly with a higher creatinine level in serum at 12 months and 24 months in patients with AT1R-Ab and/or ETAR-Ab. Conclusions: AT1R-Ab, ETAR-Ab, and HLA-DSA were associated with a higher prevalence of AMR and decline in graft function. Measurement of levels of AT1R-Ab and ETAR-Ab in KT patients may be useful for stratification of immunological risk and identification of patients at a high risk of adverse graft outcome. [ABSTRACT FROM AUTHOR]

Background Complement-binding donor-specific human leukocyte antigen (HLA) antibodies in kidney recipients have been associated with a higher risk of allograft rejection and loss. The objective of this meta-analysis was to investigate the correlation between C1q-binding donor-specific antibodies (DSAs) and clinical outcomes in kidney transplantation (KT) recipients. Methods We conducted systematic searches in the PubMed, EMBASE, and the Cochrane Library databases to identify all studies since inception to August 2021 that compared clinical outcomes between C1q + DSA and C1q-DSA patients who underwent KT. Data were independently extracted by two reviewers who assessed the risk of bias. Data were summarized with fixed effects or random effects models according to heterogeneity. We assessed clinical outcomes including graft loss, rejection, delayed graft function (DGF), and all-cause patient death. Results Twenty-six studies with a total of 1337 patients were included: 485 with C1q-binding DSAs, and 850 without C1q-binding DSAs. Compared with the C1q-DSA group, the C1q + DSA group had significant increases in antibody-mediated rejection (AMR) (relative risk [RR] = 2.09, 95% confidence interval [CI], 1.53–2.86; P < 0.00001), graft loss (RR = 2.40, 95% CI, 1.66–3.47; P < 0.00001), and death (RR = 3.13, 95% CI, 1.06–9.23; P = 0.04). The C1q + DSA and C1q-DSA groups did not show significant differences in T-cell-mediated rejection, acute rejection, acute cellular rejection, mixed rejection, or DGF. Conclusion The findings of this systematic review suggest that C1q + DSA KT have a higher risk of AMR, graft loss, and death compared with C1q-DSA patients. Monitoring C1q-binding DSAs allows risk stratification of recipients and guides physician management. [ABSTRACT FROM AUTHOR]