Rationale & Objective Recent studies showed that antibody titers after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the dialysis population are diminished as compared to the general population, suggesting the possible value of a third booster dose. We aimed to characterize the humoral response after three doses of the BNT162b2 vaccine in patients treated with either maintenance hemodialysis (HD) or peritoneal dialysis (PD). Study Design Case series. Setting & Participants 69 French patients (38 HD and 31 PD) treated at a single center who received three doses of the BNT162b2 vaccine. Findings Humoral response was evaluated using plasma levels of anti-SARS-CoV-2 spike protein S1 immunoglobulin measured after the second dose and at least three weeks after the third dose of the BNT162b2 vaccine. Patients (median age 68 [IQR, 53-76] years, 65% men) had a median anti-S1 antibody level of 284 [IQR, 83-1190] AU/mL after the second dose, and 7554 [IQR, 2268-11736] AU/mL after the third dose. Three patients were non-responders (anti-S1 antibody level < 0.8 AU/mL) and 12 were weak responders (anti-S1 antibody level 0.8-50 AU/mL) after the second vaccine dose. After the third dose, one of the three initial non-responders produced anti-spike antibody and all the 12 initial weak responders increased their antibody levels. Patients with a greater increase in anti-S1 antibody levels after a third dose had lower antibody levels after the second dose, and a longer time interval between the second and the third dose. Adverse events did not seem to be more common or severe following a third vaccine dose. Limitations Observational study, small sample size. Relationship between antibody levels and clinical outcomes is not well understood. Conclusions A third dose of the BNT162b2 vaccine substantially increased antibody levels in patients receiving maintenance dialysis and appeared to be as well tolerated as a second dose.

Introduction Les patients dialysés ont une réponse vaccinale plus faible, et sont exposés à une morbimortalité plus importante que la population générale en cas d’infection par le SARS-CoV-2. Cependant, l’efficacité de la réponse vaccinale anti-SARS-CoV-2 reste peu étudiée dans cette population. Description L’objectif de cette étude était d’évaluer la réponse humorale au vaccin BNT162b2, et les facteurs associés à la réponse vaccinale chez des patients traités par hémodialyse (HD) et par dialyse péritonéale (DP). Méthodes Cette étude rétrospective a inclus 85 patients ( n = 45 HD, n = 40 DP), ayant reçu deux doses du vaccin BNT162b2. La réponse vaccinale était évaluée par le titre d’anticorps anti-protéine spike, dosé au moins 10 jours après la deuxième dose vaccinale. Un titre d’anticorps anti-spike inférieur à 0,8 UI/mL correspondait à une non-réponse et un titre inférieur au 10 e percentile (< 10 UI/mL) était considéré comme une faible réponse vaccinale. Résultats L’âge médian était de 66 ans [intervalle interquartile : 54 ; 77] et 64,7 % étaient des hommes. Après un délai médian de 50 jours [29 ; 58], le titre médian d’anticorps anti-spike était de 250 UI/mL [87 ; 250]. Cinq (5,9 %) patients étaient non-répondeurs et 11 (12,9 %) étaient faiblement répondeurs. La réponse vaccinale n’était pas différente selon la modalité de dialyse (91,2 % en HD, 97,5 % en DP). En analyse multivariée, les facteurs associés à une plus faible réponse vaccinale étaient l’âge (β par année supplémentaire : −1,50 [IC95 % : −2,88 ; −0,13], p = 0,03), une immunosuppression (β : −52,71 [−99,59 ; −5,84], p = 0,03), le statut nutritionnel (β pour l’augmentation d’1 g/L de l’albuminémie : 3,89 [0,08 ; 7,70], p = 0,045). Conclusion La réponse vaccinale n’était pas différente selon la modalité de dialyse. L’âge, la présence d’une immunosuppression et une altération de l’état nutritionnel étaient indépendamment associés à une plus faible réponse vaccinale.

Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common Mendelian kidney diseases, that can progress to end-stage kidney failure. Pathological variants in PKD1 or PKD2 genes are found in about 78% and 15% respectively. Additional variants in genes such as GANAB, DNAJB11, and ALG8/5 have been identified in ADPKD. The sequencing of PKD1 by short read sequencing technics with exome capture such as Exome sequencing (ES) has been describe as technically challenging given 6 pseudogenes with more than 98% homology in PKD1 exonic regions 1 to 33. Moreover, the presence of repeated motifs and GC-rich in PKD1/2 add difficulties. We study the relevance of exome sequencing (ES) “first-hand” during autosomal dominant polycystic kidney disease. Method ES was performed in 684 unrelated adult patients with kidney disease from the department of Nephrology of Sorbonne University, Paris, France. Genomic DNA was extracted and exonic coding regions (37 megabases) were enriched with the Twist Human Core Exome kit, and paired-end sequenced on NextSeq500 (Illumina) machine. Sequences were analyzed with in-house and the SeqOne v1.3,2019 pipelines according to GATK4 best practices. If necessary, co-segregation of pathological variants was studied by Sanger sequencing in relatives. Results Of the 684 patients, 143 had renal cysts. Pathogenic or probably pathogenic variations in the PKD1, PKD2, and DNAJB11 genes have been identified in 26 patients, all with cystic disease; with respectively 17 variants in PKD1, 6 variants in PKD2 and 3 variants in DNAJB11. In this cohort, 18.2% of the 17 pathogenic variants are reported in PKD1, and 14 (82%) are included in exons 1 to 33. All variants were eventually confirmed by Sanger sequencing without false positive. Moreover, in 5 of the 26 patients diagnosed (19%), meaningful additional genetic data have been found, falling either in CFTR, DHCR7, HFE, F8, or ACTA2 gene. Conclusion ES highlights PKD1 and PKD2 pathogenic variants detection without false positive. This strategy allowed us to provide appropriate genetic counseling (CFTR, DHCR7), as management of yet unexpected additional genetic diseases that can affect ADPKD (F8, HFE, and ACTA2) phenotype. Given these preliminary data, ES appears effective for PKD1/PKD2 variant detection, providing additional information for ADPKD management in 20% of cases.