HLA-DR/DQ eplet mismatch predicts de novo donor-specific antibody development in multi-ethnic Southeast Asian kidney transplant recipients on different immunosuppression regimens.

Eplet mismatch has been recognized as a more precise strategy for determining HLA compatibility by analyzing donor-recipient HLA differences at the molecular level. However, predicting post-transplant alloimmunity using single-molecule eplet mismatch categories has not been validated in Asian cohorts. We examined a cohort of Southeast Asian kidney transplant recipients (n = 234) to evaluate HLA-DR/DQ eplet mismatch as a predictor of de novo donor-specific antibody (dnDSA) development. HLA-DR/DQ single-molecule eplet mismatch was quantified using HLA Matchmaker, and we utilized previously published HLA-DR/DQ eplet mismatch thresholds to categorize recipients into alloimmune risk groups and evaluate their association with dnDSA development. Recognizing that the predominance of cyclosporine use (71%) may alter published eplet mismatch thresholds derived from a largely tacrolimus-based (87%) cohort, we evaluated cohort-specific thresholds for HLA-DR/DQ single-molecule eplet mismatch categories. Recipient ethnicities included Chinese (65%), Malays (17%), Indians (14%), and others (4%). HLA-DR/DQ dnDSA developed in 29/234 (12%) recipients after a median follow-up of 5.4 years, including against isolated HLA-DR (n = 7), isolated HLA-DQ (n = 11), or both (n = 11). HLA-DR/DQ single-molecule eplet mismatch risk categories correlated with dnDSA-free survival (p = 0.001) with low-risk recipients having a dnDSA prevalence of 1% over 5 years. The cohort-specific alloimmune risk categories improved correlation with HLA-DR/DQ dnDSA-free survival and remained significant after adjusting for calcineurin inhibitor and anti-metabolite immunosuppression (p < 0.001). We validated the performance of single-molecule eplet mismatch categories as a prognostic biomarker for HLA-DR/DQ dnDSA development in a cohort of predominantly Asian kidney transplant recipients after adjusting for different immunosuppression regimens.

Analyzing COVID-19 Vaccine Responses in Transplant Recipients.

COVID-19 vaccination has significantly impacted the global pandemic by reducing the severity of infection, lowering rates of hospitalization, and reducing morbidity/mortality in healthy individuals. However, the degree of vaccine-induced protection afforded to renal transplant recipients who receive forms of maintenance immunosuppression remains poorly defined. This is particularly important when we factor in the emergence of SARS-CoV-2 variants of concern (VOCs) that have defined mutations that reduce the effectiveness of Ab responses targeting the Spike Ags from the ancestral Wuhan-Hu-1 variants employed in the most widely used vaccine formats. In this study, we describe a qualitative, longitudinal analysis of neutralizing Ab responses against multiple SARS-CoV-2 VOCs in 129 renal transplant recipients who have received three doses of the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Our results reveal a qualitative and quantitative reduction in the vaccine-induced serological response in transplant recipients versus healthy controls where only 51.9% (67 of 129) made a measurable vaccine-induced IgG response and 41.1% (53 of 129) exhibited a significant neutralizing Ab titer (based on a pseudovirus neutralization test value >50%). Analysis on the VOCs revealed strongest binding toward the wild-type Wuhan-Hu-1 and Delta variants but none with both of the Omicron variants tested (BA1 and BA2). Moreover, older transplant recipients and those who are on mycophenolic acid as part of their maintenance therapy exhibited a profound reduction in all of the analyzed vaccine-induced immune correlates. These data have important implications for how we monitor and manage transplant patients in the future as COVID-19 becomes endemic in our populations.

Clinical characteristics, outcomes, and management of COVID-19 in kidney transplant recipients across Asia: an ASTREGO report.

Background: Asia is the global epicenter of the coronavirus disease 2019 (COVID-19) pandemic; however, COVID-19-related mortality in Asia remains lower than in other parts of the world. It is uncertain whether the mortality of COVID-19-infected kidney transplant recipients (KTXs) from Asia follows the lower mortality trends of the younger Asian population. Methods: Specific transplant centers from countries in the Asian Society of Transplantation were invited to participate in a study to examine the epidemiology, clinical features, natural history, and outcomes of COVID-19 infections in KTXs. Data were analyzed and compared with those of large cohort studies from other countries. Results: The study population was 87 KTXs from nine hospitals in seven Asian countries. Within the study population, 9% were aged 60 years and older, and 79% had at least one comorbidity. The majority of patients (69%) presented with mild-to-moderate COVID-19 severity. Disease progression was more frequently encountered among those with moderate or severe infection (23%) and non-survivors (55%). The mortality rate was 23% (n=20) and differed according to the level of care 12% (n=1/8), 15% (n=10/67), and 100% (n=9/9) of patients managed as outpatients, in the general ward, and in the intensive care unit, respectively. Disease severity at the time of presentation was an independent predictor of mortality. Compared with the mortality rates in other studies worldwide, mortality rates in the current study were comparable. Conclusions: Mortality in Asian KTXs who were infected with COVID-19 remains high and could be related to comorbidity burden and the constraints of the general healthcare system when the COVID-19 caseload is high.

Comparison of cardiovascular mortality in hemodialysis versus peritoneal dialysis.

PURPOSE: Cardiovascular disease is a significant cause of morbidity and mortality in dialysis patients. With the increasing prevalence of dialysis patients, there is a need to systematically identify the epidemiology of cardiovascular disease in hemodialysis and peritoneal dialysis patients. METHODS: A meta-analysis was conducted in reference to the MOOSE and PRISMA guidelines. Database searches were conducted on Medline and Embase on 17 March 2020. Meta-analysis of proportions was used to summarize the overall prevalence of events. Pairwise comparisons were used to compare between hemodialysis and peritoneal dialysis, and meta-regression was applied to identify the factors influencing disease. RESULTS: A total of 28 studies were included in the review and prevalence of cardiovascular disease events including coronary artery disease, coronary artery complications, congestive heart failure, peripheral arterial disease, atrial fibrillation, and cardiovascular mortality were summarized. Atrial fibrillation (RR 1.287 CI 1.154-1.436, p < 0.001), congestive heart failure (RR 1.229 CI 1.074-1.407, p = 0.003), and peripheral arterial disease (RR 1.132 CI 1.021-1.255, p = 0.019) were more common in hemodialysis patients, but cardiovascular mortality was lower in hemodialysis relative to peritoneal dialysis patients. (RR 0.892 CI 0.828-0.960, p = 0.002). CONCLUSION: The authors have found fewer cardiovascular events but higher cardiovascular mortality in patients on PD as compared to those on HD. Future research is required to establish the causality between dialysis modality and the cardiovascular outcomes described.