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.

An outpatient model of care for COVID-19 infected kidney transplant patients - The hospital-at-home.

BACKGROUND: The COVID-19 pandemic is protracted and episodic surges from viral variants continue to place significant strain on healthcare systems. COVID-19 vaccines, antiviral therapy and monoclonal antibodies have significantly reduced COVID-19 associated morbidity and mortality. Concurrently, telemedicine has gained acceptance as a model of care and a tool for remote monitoring. These advances allow us to safely transit our inpatient-based care for COVID-19 infected kidney transplant recipients (KTRs) to a hospital-at-home (HaH) model of care. METHODS: KTRs with PCR-proven COVID-19 infection were triaged by teleconsult and laboratory tests. Suitable patients were enrolled into the HaH. Remote monitoring via teleconsults were conducted daily until patients were de-isolated based on a time-based criterion. Monoclonal antibodies were administered in a dedicated clinic where indicated. RESULTS: Eighty-one KTRs with COVID-19 were enrolled into the HaH between February and June 2022, 70 (86.4%) completed HaH recovery without complications. Eleven (13.6%) patients required inpatient hospitalization for medical issues (n = 8) and weekend monoclonal antibody infusion (n = 3). Patients requiring inpatient hospitalization had longer transplant vintage (15 years vs. 10 years, p = .03), anaemia (haemoglobin 11.6 g/dL vs. 13.1 g/dL, p = .01), lower eGFR (39.8 vs. 62.9 mL/min/1.73 m2 , p < .05) and lower RBD levels (<50 AU/mL vs. 1435 AU/mL, p = .02). HaH saved 753 inpatient patient-days with no deaths observed. Hospital admission rates from the HaH programme was 13.6%. Patients who required inpatient care had direct access admission without utilization of emergency department resources. CONCLUSION: Selected KTRs with COVID-19 infection can be safely managed in a HaH programme; alleviating strain on inpatient and emergency healthcare resources.

Regional citrate anticoagulation vs systemic heparin anticoagulation for double-filtration plasmapheresis.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) has been utilized for immunomodulation in kidney transplantation. Anticoagulation is important to maintain circuit patency during DFPP. We aimed to compare the efficacy and safety of regional citrate anticoagulation (RCA) with systemic heparin anticoagulation during DFPP in kidney transplant recipients. METHODS: A retrospective cohort study was conducted to compare the efficacy and safety of RCA (RCA-DFPP) to systemic heparin anticoagulation (Hep-DFPP) for DFPP among kidney transplant recipients in a single tertiary center. RESULTS: A total of 112 sessions of DFPP were performed for 23 subjects, of which 62 sessions were RCA-DFPP and 50 sessions were Hep-DFPP. There were 13 sessions (11.6%) of premature circuit clotting, 10 sessions (16.1%) for RCA-DFPP and 3 sessions (6.0%) for Hep-DFPP (P = .10). All premature circuit clotting episodes occurred in subjects who underwent DFPP through a vascular catheter. Premature circuit clotting was associated with the use of a vascular catheter (odds ratio [OR] 14.2, 95% confidence interval [CI] 2.7-73.7; P < .01) and high postfilter ionized calcium (OR 12.7, 95% CI 1.4-112.5; P < .01). There was no major bleeding event. Hep-DFPP was associated with higher occurrence of hypocalcemia (OR 1.1, 95% CI 1.0-1.2; P < .01) and metabolic acidosis (OR 1.4, 95% CI 1.2-2.0; P = .04), while hypomagnesemia was more common for RCA-DFPP (OR 2.9, 95% CI 1.1-7.4; P = .03). CONCLUSION: Amongst kidney transplant patients who receive DFPP therapy, RCA-DFPP may be comparable to Hep-DFPP for the maintenance of circuit patency. Functioning vascular access is vital in avoiding premature clotting of the circuit. Close monitoring of electrolyte imbalances and coagulopathy related to DFPP is recommended.

Regional Citrate Anticoagulation during Double-Filtration Plasmapheresis in Kidney Transplant Recipients: A Single-Center Retrospective Cohort Study.

INTRODUCTION: Double-filtration plasmapheresis (DFPP) may be used for immunomodulation in kidney transplant (KTx). While DFPP reduces plasma product exposure, risk of circuit clotting merits adequate anticoagulation. Regional citrate anticoagulation (RCA) avoids the risks of systemic anticoagulation, but a protocol for RCA-DFPP is not previously widely described. METHODS: We conducted a single-center retrospective cohort study involving adult (≥21 years old) KTx recipients who underwent RCA-DFPP from 2018 to 2020 to investigate efficacy and safety for an RCA protocol during DFPP in KTx recipients. RESULTS: Fifty-one (85%) of 60 RCA-DFPP sessions in 17 patients completed without circuit clotting. Circuit clotting was associated with high post-filter ionized calcium (28 vs. 3.7%, odds ratio 10.1, 95% CI 1.1-89.4, p = 0.037). Hypo- and hypercalcemia developed in 5 (8.3%) and 8 (13.3%) sessions, respectively, but no adverse effects were noted despite severe hypocalcemia in one. There was no significant change in pre- and post-RCA-DFPP sodium, bicarbonate, albumin, and platelet levels. With regards DFPP procedure, prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) was observed following 38 (64.4%) and 12 (20.3%) sessions, respectively. Severely prolonged (>1.5 × upper limit normal) PT and aPTT were recorded in 2 sessions each. Expectedly, hypofibrinogenemia developed after 31 (51.7%) sessions: including 4 (6.7%) severe hypofibrinogenemia (<0.5 g/L). Two patients developed bleeding requiring blood product transfusion. The median total volume of fluids administered per session was 1.495 (1.373-1.612) L; post-RCA-DFPP significant weight gain of 0.5 (0-1.25) kg was noted. Diuretic was commenced or dose increased following 20 (33.3%) sessions for fluid balance management. DISCUSSION/CONCLUSION: Protocol-based RCA for DFPP is feasible and safe in KTx recipients. However, DFPP-related coagulopathy can develop consequent to treatment; caution should be exercised for patients with bleeding risk. Close monitoring and management of the patients' electrolytes, especially hypocalcemia and hypomagnesemia, and fluid status is recommended.

Psychological distress and associated factors among kidney transplant recipients and living kidney donors during COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant psychological distress globally. Our study assessed the prevalence of psychological distress and associated factors during COVID-19 pandemic among kidney transplant recipients and kidney donors. METHODS: A cross-sectional survey of 497 participants (325 recipients and 172 donors) was conducted from 1st May to 30th June 2020 in Singapore. The survey questionnaire assessed knowledge levels of COVID-19, socio-demographic data, health status, psychosocial impact of COVID-19, and precautionary behaviors during the pandemic. Psychological distress was defined as having anxiety, depression, or stress measured by the validated Depression, Anxiety and Stress Scale-21. Linear regression analyses were used to assess factors associated with higher psychological distress. RESULTS: The prevalence of psychological distress was 14.3% (95% confidence interval: 11.5-17.6%) in the overall population; it was 12.8% (9.79-16.6%) in recipients and 13.4% (9.08-19.6%) in donors with no significant difference (P = 0.67). Younger age (21-49 vs. ≥50 years), unmarried status, non-Singapore citizen, worse health conditions, and worrying about physical and mental health were associated with higher psychological distress. Malays (versus Chinese), taking precautionary measures (hand sanitization), and receiving enough information about COVID-19 were associated with lower psychological distress. No interactions were observed between recipients and donors. CONCLUSIONS: At least one in ten recipients and donors suffer from psychological distress during COVID-19 pandemic. Focused health education to younger adults, unmarried individuals, non-Singapore citizens, and those with poor health status could potentially prevent psychological distress in recipients and donors.

Aviremic organ transplant dengue virus transmission - A case report.

Dengue virus (DENV), a mosquito-borne pathogen, causes systemic infections. There are no clear guidelines regarding the screening of donor blood is used in endemic countries to prevent blood transfusion or transplant-associated dengue. DENV has been shown to be detected in urine samples even when DENV viremia is undetectable. We describe an incident of transplant-associated dengue where the donor tested negative for DENV viremia but positive for DENV viuria resulting in the transmission of DENV to our two kidney recipients. Both recipients resolved DENV infection uneventfully, with no adverse impact on the renal graft. Our findings raise the consideration for revised screening recommendations in endemic countries to include DENV RT-PCR in the urine.

Hepatitis C virus antigen detection is an appropriate test for screening and early diagnosis of hepatitis C virus infection in at-risk populations and immunocompromised hosts.

Early diagnosis remains key for effective prevention and treatment. Unfortunately, current screening with anti-hepatitis C virus antibody (anti-HCV Ab) test may have limited utility in the diagnosis of HCV infection and reinfection. This is of special concern to at-risk population, such as immunocompromised hosts and end-stage renal failure patients on hemodialysis. HCV antigen (Ag) could be useful in identifying the ongoing infection in such clinical scenarios. Hence, we aimed to study the utility of HCV Ag testing for the diagnosis of acute and chronic hepatitis C. Of 89 samples studied, 19 were from acute hepatitis C patients who were immunocompromised or were on hemodialysis, 43 were from active chronic hepatitis C patients and 27 were from patients treated for chronic hepatitis C. All samples were tested for HCV Ag using the Abbott ARCHITECT HCV Ag assay. HCV Ag was reactive in 19/19 samples from acute hepatitis C patients and 42/43 samples from active chronic hepatitis C patients. It was nonreactive in all samples from treated patients. The test showed a sensitivity and specificity of 98.4% and 100.0%, respectively. The positive and negative predictive values were 100.0% and 96.4%, respectively. The HCV antigen test has high clinical sensitivity and specificity and is useful for the diagnosis of acute and chronic hepatitis C infection in at-risk and immunocompromised patients. Its short turnaround time and relatively low cost are advantageous for use in patients on hemodialysis and other at-risk patients who require monitoring of HCV infection and reinfection.

Cytomegalovirus-associated pseudomembranous colitis in a kidney transplant recipient.

Pseudomembranous colitis (PMC) is classically associated with Clostridium difficile infection. We report a rare case of cytomegalovirus (CMV)-associated PMC in a 52-year-old female patient who had undergone kidney transplantation more than 20 years ago and was on low dose prednisolone and ciclosporin. She presented with an acute history of fever, lethargy, vomiting and diarrhoea on admission. Computed tomography of the abdomen showed extensive colitis, and colonoscopy revealed extensive pseudomembrane formation. Multiple tests for Clostridium difficile and other common microbiological causes of colitis were negative. CMV DNAemia and colonic biopsies confirmed the diagnosis of CMV colitis. The patient responded to prompt CMV treatment, as demonstrated by clinical, endoscopic, and histological response. While CMV is a common pathogen in the solid organ transplant population that is familiar to most transplant physicians, it may present atypically as PMC. Here, we review the literature on CMV-associated PMC and its relevance to solid organ transplant recipients. To our knowledge, this is the first reported case of CMV-associated PMC in a kidney transplant recipient.

Coronavirus disease 2019 in kidney transplant recipients: a systematic review and meta-analysis.

Introduction: The clinical presentation and outcomes of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs) have not been well studied. Methods: We performed a meta-analysis to examine the presenting features, outcomes and the effect of treatment on outcomes of KTRs with COVID-19. Database search was performed up to 5 September 2020 through PubMed, Embase, Web of Science, Scopus and CENTRAL. Results: Overall, 23 studies (1,373 patients) were included in the review and meta-analysis. The most common presenting symptoms included fever (74.0%, 95% confidence interval [CI] 65.3-81.1), cough (63.3%, 95% CI 56.5-69.6) and dyspnoea (47.5%, 95% CI 39.6-55.6). Pooled rates of mortality and critical illness were 21.1% (95% CI 15.3-28.4) and 27.7% (95% CI 21.5-34.8), respectively. Acute kidney injury occurred in 38.9% (95% CI 30.6-48.1) and dialysis was required in 12.4% (95% CI 8.3-18.0) of the cases. Conclusion: Kidney transplant recipients with COVID-19 have a similar clinical presentation as the general population, but they have higher morbidity and mortality. It is uncertain whether high-dose corticosteroid or hydroxychloroquine reduces the risks of mortality in KTRs with COVID-19.

COVID-19 vaccine acceptance among kidney transplant recipients in Singapore.

Introduction: A successful vaccination programme forms the cornerstone of controlling coronavirus disease 2019 (COVID-19). The unprecedented speed of COVID-19 vaccine development and lack of long-term data have raised fears regarding its safety and efficacy. Vaccine hesitancy can undermine the uptake, and hence success of the vaccination programme. Given the high complication rates of COVID-19 infections in kidney transplant recipients, it is particularly important to identify and address vaccine hesitancy in this population. Methods: We conducted a cross-sectional survey among kidney transplant recipients attending transplant clinic between 5 April and 5 May 2021. The survey assessed attitudes towards COVID-19, willingness/hesitancy towards COVID-19 vaccination, vaccination concerns and prompts to vaccination. This was scored on a Likert scale with scores ranging from 'strongly disagree' - 1 point to 'strongly agree' - 5 points. Results: One hundred and one completed responses were captured. Of these, 86% respondents reported to agree or strongly agree to vaccination. This was despite significant concerns of allograft rejection (mean score 4.12, standard deviation [SD] 0.97) and decreased immunosuppressant efficacy (mean score 4.14, SD 0.96) with vaccination. Multivariable model showed a positive association with transplant vintage of ≥ 5 years (median 2.41), lower educational levels of secondary school or less (median 5.82) and healthcare provider advocacy (median 1.88) in predicting vaccine acceptance. Conclusions: Vaccine acceptance rate was high among kidney transplant recipients. Vaccine hesitancy remains a concern in those with a transplant vintage of less than 5 years and those with tertiary educational level. Healthcare provider advocacy is important in improving vaccine acceptance rates.