The effectiveness of nirmatrelvir/ritonavir regimen in hospitalized renal transplant patients with prolonged COVID-19 infection: a multicenter clinical experience.

OBJECTIVES: Effectiveness of nirmatrelvir/ritonavir (NR) in kidney transplant recipients (KTRs) infected COVID-19 for more than 5 days has not been evaluated. METHODS: In this multicenter retrospective study, 85 KTRs with COVID-19 were enrolled, including 50 moderate, 21 severe, and 14 critical patients. RESULTS: The median time from onset to starting NR treatment was 14 (IQR, 11-19) days. Before NR treatment, 96.5% patients reduced use of antimetabolites. They also stopped using calcineurin inhibitors (CNI) 12-24 hours before NR treatment, with CNI concentrations well-controlled during NR treatment. The use of intravenous corticosteroids increased with COVID-19 severity. The median time to reach viral negative conversion was 5 (IQR, 4-8) days for all patients. For moderate and severe COVID-19 patients, they had a low rate of ICU admission (1.4%), exacerbation requiring upgraded oxygen therapy (5.6%), and dialysis (2.8%); no intubation and mechanical ventilation, and no deaths were observed. Patients with critical COVID-19 had a low mortality rate (7.1%). CONCLUSIONS: A regimen including NR for clearing SARS-CoV-2 along with reducing immunosuppressants and using intravenous corticosteroids is associated with lower rates of exacerbation and mortality in KTRs who have moderate to critical SARS-CoV-2 infection and the virus still present after 5 days.

Interferon-gamma FlowSpot assay for the measurement of the T-cell response to cytomegalovirus.

Objectives: We describe a new method, FlowSpot, to assess CMV-specific T-cell response by quantification of interferon-gamma (IFN-γ). CMV-specific, T-cell-released IFN-γ was captured by flow beads and measured via flow cytometry. In the present study, we used FlowSpot to assess CMV-specific T-cell response in healthy individuals. The FlowSpot results were compared with those of serological analysis and enzyme-linked immunospot (ELISpot) assay. Methods: Experimental results and parameter analysis were investigated by using serological, ELISpot, and FlowSpot assays. Results: The levels of IFN-γ, which is released from CMV-specific T-cells, were measured, and the results and parameter analysis showed a good correlation between FlowSpot and ELISpot. However, FlowSpot was more sensitive and better reflected the strength of IFN-γ secretion than did ELISpot. Conclusions: Compared to ELISpot, FlowSpot has a high sensitivity and is cost and time effective. Thus, this method can be used in wider clinical and scientific applications.

The Outcome of Transplanting Kidneys From Very Small Pediatric Deceased Donors.

BACKGROUND: Kidneys from very small pediatric donors (VSPDs, aged <2 y) are underutilized. Concerns regarding potentially inferior outcomes hinder the use in pediatric recipients. METHODS: All pediatric kidney-only transplants from <18-year-old donors between January 2012 and May 2021 in our center were included in this study. Outcomes were compared between VSPD and normal pediatric donor (NPD, aged 2-18 y) groups, and 3-y death-censored graft survival was assessed by the multivariable Cox proportional hazard model. RESULTS: Of all 252 enrolled patients, 149 (59.1%) received kidneys from NPDs and 103 (40.9%) from VSPDs. The 3-y graft survival rates of the NPD and VSPD groups were 91.2% and 88.6%, respectively ( P = 0.385). The adjusted hazard ratio of 3-y graft loss was 1.2 (95% confidence interval, 0.6-2.5; P = 0.659) for the VSPD group compared with the NPD group. There was no significant difference in estimated glomerular filtration rate at 3 y posttransplant observed between NPD and VSPD groups (86.9 ± 26.8 versus 87 ± 27.9 mL/min/1.73 m 2 ; P = 0.991). Patients (n = 12, 4.8%) who received kidneys from donors <5 kg contributed 5 (5/39, 12.8%) with delayed graft function and the sole primary nonfunction in our cohort. CONCLUSIONS: Although attention to preventing complications is necessary, especially for kidneys from donors <5 kg, kidneys from VSPDs did not appear to impart added risk for 3-y graft loss and renal function.

Eplet-Predicted Antigens: An Attempt to Introduce Eplets into Unacceptable Antigen Determination and Calculated Panel-Reactive Antibody Calculation Facilitating Kidney Allocation.

(1) Calculated panel-reactive antibody (CPRA) is a measure of sensitization based on unacceptable antigens (UAs). Determination of UAs based on single-antigen bead assays at allele or antigen levels may be inappropriate. We aimed to introduce eplets for better assessment of sensitization; (2) 900 recipients and 1427 donors were enrolled for candidate or donor pools, respectively. Eplets were from the HLA Epitope Registry. UAs were determined by anti-HLA antibodies identified using LIFECODES Single Antigen (LSA) kits. CPRA values were calculated using a simplified method of donor filtering; (3) HLA antigens containing all eplets of an HLA antigen in LSA kits (LSA antigen) were defined as eplet-predicted (EP) antigens, the reactivity of which could be predicted by that LSA antigen. High reactivity concordance was found between LSA and EP antigens. More HLA antigens were covered by EP antigens in the population than LSA antigens. CPRA values at the EP level were higher than at the allele level and lower than at the antigen level. The EP antigens facilitated UA determination for non-LSA antigens and avoided acute rejection; (4) UA determination using EP antigens can lead to more accurate assessment of sensitization, enabling a high probability of compatible organs and a low risk of adverse outcomes.