Background There is scarce evidence on fourth doses of SARS-CoV-2 vaccines in chronic kidney disease (CKD) patients. We have evaluated the humoral response and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), hemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients. Methods This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analyzed factors associated to persistent negative humoral response and to higher anti-Spike antibody titers as well as the efficacy of vaccination on COVID-19 severity. Results Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titers in HD (P = 0.001) and ND-CKD (P = 0.014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titers at 12 months were independently associated to repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titers and not being a KT. Breakthrough COVID-19 was registered in 137 (6%) patients, of whom 5% required admission. Admitted patients had prior titers below 620 UI/ml and median values were lower (P = 0.020) than in non-admitted patients. Conclusions A fourth vaccine dose increased anti-Spike antibody titers or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titers or KT recipients) derived the least benefit in terms of antibody titers. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titers.

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