Prevalence and Impact of BK Polyomavirus in the Ureters of Kidney Donors: Research Letter.

Background: More than 75% of the population is seropositive for BK polyomavirus (BKV), which remains quiescent in the urothelium in immunocompetent hosts. However, it can reactivate in kidney transplant recipients (KTRs), and up to 30% of them will develop BKV viremia in the 2 years following transplant, with a risk of developing BKV-associated nephropathy (BKVAN). Viral reactivation is associated with the level of immunosuppression, but there is currently no way to predict which patients are at high risk for reactivation. Objective: As BKV originates from kidney donors, our primary objective was to determine the prevalence of detectable BKV in donor ureters. Our secondary objective was to see if there is a correlation between the presence of BKV in donor urothelium and the development of BKV viremia and BKVAN in KTR. Design: Prospective cohort study. Setting: Single-center academic kidney transplant program. Patients: Prospective sequential KTRs that received a kidney transplant between March 2016 and March 2017. Measurements: The presence of BKV in donor ureters was determined by TaqMan-based quantitative polymerase chain reaction (PCR; qPCR). Methods: We performed a prospective study which was done on 35 out of the 100 donors initially foreseen to take part in the study. During surgery, the distal part of donor ureter was kept and analyzed by qPCR (to establish the presence of BKV in the urothelium). The primary outcome was the development of BKV viremia in KTR over a period of 2 years after transplant. Secondary outcome was the development of BKVAN. Results: Out of 35 ureters analyzed, only one had a positive qPCR for BKV (2.86%, 95% confidence interval [CI]: [0.07-14.92]). Considering the primary objective would not be met, the study was interrupted after 35 specimens. After surgery, 9 recipients had a slow graft function and 4 had delayed graft function, one of which never recovered graft function. Over the 2-year follow-up, 13 patients developed BKV viremia, while 5 patients developed BKVAN. The patient who received a graft from a positive qPCR donor eventually developed BKV viremia and nephropathy. Limitations: The specimen analyzed was a distal rather than a proximal portion of the ureter. However, BKV replication is known to concentrate in the corticomedullary junction. Conclusion: BK polyomavirus prevalence in the distal part of donor ureters is lower than previously reported. It cannot be used as a predictor for the development of BKV reactivation and/or nephropathy.

Contexte: Plus de 75 % de la population générale est séropositive pour le polyomavirus BK (BKV), qui demeure quiescent dans l'urothélium des hôtes immunocompétents. Il peut cependant se réactiver chez les receveurs d'une greffe rénale et, chez jusqu'à 30 % d'entre eux, entraîner une virémie BKV dans les deux ans suivant la transplantation, avec un risque de développer une néphropathie associée à BKV (NA-BKV). La réactivation virale est associée au niveau d'immunosuppression, mais il n'existe actuellement aucun moyen de déterminer quels patients présentent un risque élevé de réactivation. Objectifs: Puisque le BKV provient des donneurs de rein, l'objectif principal était d'établir la prévalence du BKV détectable dans les uretères des donneurs. L'objectif secondaire était d'examiner s'il existe une corrélation entre la présence de BKV dans l'urothélium du donneur et le développement d'une virémie BKV et d'une néphropathie associée au BKV chez les greffés rénaux. Type d'étude: Étude de cohorte prospective. Cadre: Programme de transplantation rénale d'un centre hospitalier universitaire. Sujets: Les receveurs séquentiels d'une greffe rénale qui avaient subi leur intervention entre mars 2016 et mars 2017. Mesures: La présence de BKV dans les uretères des donneurs a été déterminée par PCR quantitatif (qPCR) avec sonde TaqMan. Méthodologie: Notre étude prospective porte sur 35 des 100 donneurs initialement envisagés pour participer à l'étude. Pendant l'intervention, la partie distale de l'uretère du donneur a été conservée et analysée par qPCR (pour établir la présence de BKV dans l'urothélium). Le principal critère d'évaluation était le développement d'une virémie BKV chez les greffés rénaux dans les deux ans suivant la transplantation. Le résultat secondaire était le développement d'une néphropathie associée au BKV. Résultats: Sur les 35 uretères analysés, un seul s'est avéré positif pour BKV par qPCR (2,86 %; IC 95 %: 0,07-14,92). Voyant que l'objectif principal ne serait pas atteint, l'étude a été interrompue après 35 échantillons. Après la greffe, 9 receveurs ont expérimenté une lente reprise de la fonction du greffon et 4 receveurs ont vu la fonction de leur greffon retardée; de ces derniers, une personne n'a jamais retrouvé de fonction du greffon. Pendant les deux années de suivi, 13 patients ont développé une virémie BKV et 5 patients ont développé une néphropathie associée au BKV. La personne qui avait reçu le greffon du donneur positif au qPCR a ultérieurement développé une virémie et une néphropathie associées à BKV. Limites: Les échantillons analysés provenaient de la partie distale et non de la partie proximale de l'uretère. On sait toutefois que la réplication du BKV se concentre dans la jonction corticomédullaire. Conclusion: La prévalence du BKV dans la partie distale des uretères des donneurs s'est avérée plus faible que ce qui avait été précédemment rapporté. Ce résultat ne peut être utilisé comme prédicteur de la réactivation du BKV et/ou du développement d'une néphropathie associée à BKV.

A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4+ T cell profile

Cellular immune defects associated with suboptimal responses to SARS-CoV-2 mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyzed antibody, B cell, CD4+ and CD8+ T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CI). The first two doses elicit weaker B cell and CD8+ T cell responses in HD than in CI, while CD4+ T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8+ T cell responses and enhances comparatively more Thelper (TH) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of TH cells in HD (TNF/IL-2 skewing), while others (CCR6, CXCR6, PD-1 and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieve robust multifaceted immunity in hemodialysis patients, although some distinct TH characteristics endure.

Short-term antibody response and tolerability of one dose of BNT162b2 vaccine in patients receiving hemodialysis

BackgroundPatients receiving in-center hemodialysis (HD) are at high risk of exposure to SARS-CoV-2 with high mortality, and response to vaccination is uncertain. MethodsWe obtained serial plasma from 58 HD patients and 32 health-care workers (HCW) before and after vaccination with one dose of the BNT162b2 mRNA vaccine; as well as convalescent plasma from 11 HD patients who survived COVID-19. Anti-RBD (region binding domain of the SARS-CoV-2 Spike protein) IgG and IgM levels were measured by ELISA. Groups were stratified by evidence of prior SARS-CoV-2 infection. ResultsIn HD patients without prior SARS-CoV-2, antiRBD levels were significantly lower at 4 and 8 weeks after vaccination, compared to in HCWs after 3 weeks (p<0.001), and to convalescent plasma (p=0.002). Anti-RBD IgG was non-detectable in 29/46 (63%) of HD, compared to 1/16 (6%) of HCWs (p<0.0001). No patient with non-detectable levels at 4 weeks developed antiRBD by 8 weeks. In HD patients with prior SARS-CoV-2, mean 8-week anti-RBD IgG levels were similar to controls at 3 weeks (p=0.16), and to convalescent plasma (p=0.45). No patients reported symptoms 7 days after vaccination on a standardized questionnaire. InterpretationWhile the BNT162b2 vaccine was well-tolerated in hemodialysis patients, a single dose failed to elicit a humoral immune response in the majority of SARS-CoV-2 naive patients even after prolonged observation. In those with prior SARS-CoV-2 infection, the humoral response after vaccination was delayed. Whether HD patients develop T-cell responses requires further study. Until then, we advise the second dose be administered to all HD patients at the recommended 3-week time interval, and that rigorous SARS-CoV-2 infection prevention and control measures be continued in dialysis units until vaccine efficacy is proven.