Prediction of Vaccine Response and Development of a Personalized Anti-SARS-CoV-2 Vaccination Strategy in Kidney Transplant Recipients: Results from a Large Single-Center Study.

Kidney transplant recipients (KTRs) displays marked inter-individual variations in magnitude of immune responses to anti-SARS-CoV-2 vaccination. The aim of this large single-center study was to identify the predictive factors for serological response to the mRNA-1273 vaccine in KTRs. We also devised a score to optimize prediction with the goal of implementing a personalized vaccination strategy. The study population consisted of 564 KTRs who received at least two doses of the mRNA-1273 vaccine. Anti-RBD IgG titers were quantified one month after each vaccine dose and until six months thereafter. A third dose vaccine was given when the antibody titer after the second dose was <143 BAU/mL. A score to optimize prediction of vaccine response was devised using the independent predictors identified in multivariate analysis. The seropositivity rate after the second dose was 46.6% and 22.2% of participants were classified as good responders (titers ≥ 143 BAU/mL). On analyzing the 477 patients for whom serology testing was available after the second or third dose, the global seropositivity rate was 69% (good responders: 46.3%). Immunosuppressive drugs, graft function, age, interval from transplantation, body mass index, and sex were associated with vaccine response. The devised score was strongly associated with the seropositivity rate (AUC = 0.752, p < 0.0001) and the occurrence of a good antibody response (AUC = 0.785, p < 0.0001). Notably, antibody titers declined over time both after the second and third vaccine doses. In summary, a high burden of comorbidities and immunosuppression was correlated with a weaker antibody response. A fourth vaccine dose and/or pre-exposure prophylaxis with monoclonal antibodies should be considered for KTRs who remain unprotected.

Breakthrough COVID-19 cases despite prophylaxis with 150 mg of tixagevimab and 150 mg of cilgavimab in kidney transplant recipients.

The cilgavimab-tixagevimab combination retains a partial in vitro neutralizing activity against the current SARS-CoV-2 variants of concern (omicron BA.1, BA.1.1, and BA.2). Here, we examined whether preexposure prophylaxis with cilgavimab-tixagevimab can effectively protect kidney transplant recipients (KTRs) against the omicron variant. Of the 416 KTRs who received intramuscular prophylactic injections of 150 mg tixagevimab and 150 mg cilgavimab, 39 (9.4%) developed COVID-19. With the exception of one case, all patients were symptomatic. Hospitalization and admission to an intensive care unit were required for 14 (35.9%) and three patients (7.7%), respectively. Two KTRs died of COVID-19-related acute respiratory distress syndrome. SARS-CoV-2 sequencing was carried out in 15 cases (BA.1, n = 5; BA.1.1, n = 9; BA.2, n = 1). Viral neutralizing activity of the serum against the BA.1 variant was negative in the 12 tested patients, suggesting that this prophylactic strategy does not provide sufficient protection against this variant of concern. In summary, preexposure prophylaxis with cilgavimab-tixagevimab at the dose of 150 mg of each antibody does not adequately protect KTRs against omicron. Further clarification of the optimal dosing can assist in our understanding of how best to harness its protective potential.

Atypical hemolytic and uremic syndrome due to C3 mutation in pancreatic islet transplantation: a case report.

BACKGROUND: We here report on the first observation of a C3 mutation that is related to atypical hemolytic and uremic syndrome (aHUS), which occurred in a pancreatic islet transplant patient. Immunosuppressive treatments, such as calcineurin inhibitors, have been linked to undesirable effects like nephrotoxicity. CASE PRESENTATION: A 40-year-old man with brittle diabetes, who was included in the TRIMECO trial, became insulin-independent 2 months after pancreatic islet transplantation. About 15 months after islet transplantation, the patient exhibited acute kidney injury due to aHUS. Despite plasma exchange and eculizumab treatment, the patient developed end-stage renal disease. A genetic workup identified a missense variant (p.R592Q) in the C3 gene. In vitro, this C3 variant had defective Factor I proteolytic activity with membrane proteins as cofactor proteins, which was thus classified as pathogenic. About 1 year after the aHUS episode, kidney transplantation was carried out under the protection of the specific anti-C5 monoclonal antibody eculizumab. The patient had normal kidney function, with preserved pancreatic islet function 4 years later. CONCLUSIONS: Pancreatic islet transplantation could have triggered this aHUS episode, but this link needs to be clarified. Although prophylactic eculizumab maintains kidney allograft function, its efficacy still needs to be studied in larger populations.

In-depth virological assessment of kidney transplant recipients with COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread widely, causing coronavirus disease 2019 (COVID-19) and significant mortality. However, data on viral loads and antibody kinetics in immunocompromised populations are lacking. We aimed to determine nasopharyngeal and plasma viral loads via reverse transcription-polymerase chain reaction and SARS-CoV-2 serology via enzyme-linked immunosorbent assay and study their association with severe forms of COVID-19 and death in kidney transplant recipients. In this study, we examined hospitalized kidney transplant recipients with nonsevere (n = 21) and severe (n = 19) COVID-19. SARS-CoV-2 nasopharyngeal and plasma viral load and serological response were evaluated based on outcomes and disease severity. Ten recipients (25%) displayed persistent viral shedding 30 days after symptom onset. The SARS-CoV-2 viral load of the upper respiratory tract was not associated with severe COVID-19, whereas the plasma viral load was associated with COVID-19 severity (P = .010) and mortality (P = .010). All patients harbored antibodies during the second week after symptom onset that persisted for 2 months. We conclude that plasma viral load is associated with COVID-19 morbidity and mortality, whereas nasopharyngeal viral load is not. SARS-CoV-2 shedding is prolonged in kidney transplant recipients and the humoral response to SARS-CoV-2 does not show significant impairment in this series of transplant recipients.

[Emergency vascular access conversion to native arterio veinous fistula: a prospective study of 37 hemodialysis patients in Rwanda]. / Conversion des abords vasculaires d'urgence pour hémodialyse en fistules natives au Rwanda : à propos de 37 cas.

UNLABELLED: Chronic hemodialysis in Rwanda is relatively recent and most of patients are treated with catheters. SUMMARY: Thirty-seven patients who require chronic hemodialysis with catheters were evaluated during a 3-years period in order to facilitate the creation of a permanent vascular access for hemodialysis (AVF). Patient selection were made during a multi-disciplinary consultation. The sex-ratio was 1.5 and the main cause of the nephropathy was arterial hypertension. RESULTS: Thirty-one patients benefited from the creation of an arterioveinous fistula. All of the interventions were performed using local or loco-regional anesthesia. Sixty percent of these AVF were radio-cephalic, 35.4% were humero-cephalic. Sixty-four percent of the operations were performed on ambulatory patients, with a primary function for 90% of them. CONCLUSION: This work proves the feasibility of the creation of AVF in Rwanda, thus allowing to preclude the various complications that arise with the prolonged use of a catheter. This experience was made possible by the pooling of the resources of 4 of Rwanda's leading hospitals. In an early future, the development of vascular surgery will assure the permanence of this care.

Risk factors for BK virus infection in the era of therapeutic drug monitoring.

BACKGROUND: Overimmunosuppression is a widely recognized risk factor for BK virus (BKV) infection, particularly with the combination of tacrolimus, mycophenolate mofetil (MMF), and steroids. Nevertheless, the exact impact of exposure to tacrolimus and MMF is not well understood. METHODS: We examined 240 kidney recipients between 2006 and 2008. BKV was monitored every 2 months in the urine or blood. A kidney biopsy was performed when viremia exceeded 10 copies/mL. RESULTS: Ninety-five (40%) patients had sustained viruria, 48 (20%) sustained viremia, and 17 (7%) biopsy-proven polyomavirus-associated nephropathy. The mean time-to-occurrence was 7.6, 7.9, and 9.7 months for viruria, viremia, and polyomavirus-associated nephropathy. Risk factors associated with BKV infection in univariate analyses were retransplantation, panel-reactive antibody more than 0%, cytomegalovirus D+/R-, cold ischemia time, delayed graft function, induction with antithymocyte globulins, acute rejection before month 3 (M3), tacrolimus trough levels more than 10 ng/mL, and M3 AUC0-12 hr more than 50 hr mg/L. Multivariate analyses showed that cytomegalovirus D+/R- (adjusted hazard ratio [AHR], 2.03; P=0.05), acute rejection (AHR, 5.4; P<0.001), and mycophenolic acid AUC0-12 hr more than 50 hr mg/L (AHR, 3.6; P=0.001) were risk factors for BKV. CONCLUSIONS: This study identified a link between a state of increased immunosuppression and BKV infection, especially in patients with higher MMF exposure and elevated tacrolimus trough levels at M3.