Unrepresented human leucocyte antigen alleles in single-antigen bead assays: A single-centre cohort study.

Human leucocyte antigen (HLA) alleles may generate antibodies that are undetectable by routine single-antigen beads (SABs) assays if their unique epitopes are unrepresented. We aimed to describe the prevalence and explore the potential impact of unrepresented HLA alleles in standard SAB kits in our cohort. All individuals who had undergone two-field HLA typing (HLA-A/B/C/DRB1/DQA1/-DQB1/-DPA1/-DPB1) from February 2021 to July 2023 were included. Two-field HLA-DRB3/4/5 typing was imputed. Each unrepresented allele was compared with the most similar represented allele in the standard LABScreen, LABScreen ExPlex (One Lambda) and the LIFECODES (Immucor) SAB kits. Differences in eplet expression (HLA Eplet Registry) were identified. Differences in three-dimensional molecular structures were visualized using generated models (SWISS-MODEL). Two-field HLA typing was performed for 116 individuals. Overall, 16.7% of all HLA alleles, found in 36.2% of individuals, were unrepresented by all SAB test kits. Four eplets, found in 12.9% of individuals, were unrepresented in at least 1 SAB kit. Non-Chinese individuals were more likely to have unrepresented HLA alleles and eplets than Chinese individuals. There were differences in HLA allele and eplet representation amongst the different SAB test kits. Use of supplementary SAB test kits may improve HLA allele and eplet representation. Although some HLA alleles were unrepresented, most epitopes were represented in current SAB kits. However, some unrepresented alleles may contain epitopes which may generate undetectable antibodies. Further studies may be needed to investigate the potential clinical impact of these unrepresented alleles and eplets, especially in certain ethnic populations or at-risk individuals.

Diagnostic threshold and performance of anion gap in screening for high anion gap metabolic acidosis.

INTRODUCTION: The anion gap (AG) is commonly used to screen for acid-base disorders. It was proposed that the cut-off for high anion gap metabolic acidosis (HAGMA) may be lower with current laboratory techniques, although modern laboratory equipment are still calibrated to familiar reference ranges established with earlier techniques. The appropriate cut-off for HAGMA is unclear. This study aimed to assess the performance of AG as a screening test for HAGMA and to determine the optimal diagnostic threshold of AG for HAGMA. METHODS: This was a retrospective analysis of a large, anonymised dataset extracted by computerised protocol from 2017 to 2019. All inpatients with blood samples taken for organic acids (lactate, ketone or salicylate) paired with a metabolic panel were included. The target condition was HAGMA secondary to elevated blood lactate, ketone and/or salicylate. Sensitivity for HAGMA was explored at various AG cut-off levels. RESULTS: Of 16,475 patients, 2,621 had organic acidosis. Median age was 65 years, and median estimated glomerular filtration rate was 70 mL/min/1.73 m2. With organic acidosis, the median AG was 23 (interquartile range [IQR] 20-29) mEq/L, while without organic acidosis, the median AG was 16 (IQR 14-19) mEq/L. The area under the curve-receiver operating characteristic of AG for HAGMA was 0.873. Desired sensitivity for HAGMA was set at ≥95%, and this was found with an AG threshold of ≥15 mEq/L (sensitivity 98.1%, specificity 34.0%). CONCLUSION: The recommended AG threshold value is ≥15 mEq/L with a high sensitivity for HAGMA. The AG should always be interpreted with the clinical context, and it should be repeated as the clinical picture evolves.

Safely navigating kidney transplantation during the COVID-19 pandemic: the Singapore General Hospital's experience.

Background: The coronavirus disease 2019 (COVID-19) pandemic curtailed transplant activities worldwide, driven by concerns about increased COVID-19-related mortality among kidney transplant recipients (KTRs), infections originating from donors, and decreased availability of surgical and intensive care resources as healthcare resources are reallocated for pandemic response. We examined the outcomes of KTRs at our center before and during the COVID-19 pandemic. Methods: We conducted a retrospective single-center cohort study examining the characteristics and outcomes of patients undergoing kidney transplantation during two periods January 1, 2017 to December 31, 2019 (pre-COVID-19 era) and January 1, 2020 to June 30, 2022 (COVID-19 era). We reviewed perioperative and COVID-19 infection-related outcomes in both groups. Results: A total of 114 transplants were performed during the pre-COVID-19 era, while 74 transplants were conducted during the COVID-19 era. No differences in baseline demographics were observed. Additionally, there were no significant differences in perioperative outcomes, except for a longer cold ischemia time during the COVID-19 era. However, this did not result in an increased incidence of delayed graft function. Among the KTRs infected with COVID-19 during the pandemic era, no severe complications such as pneumonia, acute kidney injury, or death were reported. Conclusions: With the global transition to an endemic phase of COVID-19, it is imperative to revitalize organ transplant activities. Effective containment workflow, good vaccination uptake, and prompt COVID-19 treatment are essential to ensure that transplants can proceed safely.