Poor neutralization and rapid decay of antibodies to SARS-CoV-2 variants in vaccinated dialysis patients.

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.

Consequences of Supraphysiological Dialysate Magnesium on Arterial Stiffness, Hemodynamic Profile, and Endothelial Function in Hemodialysis: A Randomized Crossover Study Followed by a Non-Controlled Follow-Up Phase.

INTRODUCTION: Increasing dialysate magnesium (D-Mg2+) appears to be an intriguing strategy to obtain cardiovascular benefits in subjects with end-stage kidney disease (ESKD) on hemodialysis. To date, however, hemodialysis guidelines do not suggest to increase D-Mg2+ routinely set at 0.50 mmol/L. METHODS: A randomized 4-week crossover study aimed at investigating the consequences of increasing D-Mg2+ from 0.50 to 0.75 mmol/L on arterial stiffness, hemodynamic profile, and endothelial function in subjects undergoing hemodialysis. The long-term effect of higher D-Mg2+ on mineral metabolism markers was investigated in a 6-month follow-up. Data were analyzed by linear mixed models for repeated measures. RESULTS: Data of 39 patients were analyzed. Pulse wave velocity and pulse pressure significantly decreased on the higher D-Mg2+ compared with the standard one by - 0.91 m/s (95% confidence interval - 1.52 to - 0.29; p = 0.01) and - 9.61 mmHg (- 18.89 to - 0.33, p = 0.04), respectively. A significant reduction in systolic blood pressure of - 12.96 mmHg (- 24.71 to - 1.22, p = 0.03) was also observed. No period or carryover effects were observed. During the long-term follow-up phase the higher D-Mg2+ significantly increased ionized and total serum Mg (respectively from 0.54 to 0.64 and from 0.84 to 1.07 mmol/L; mean percentage change from baseline to follow-up + 21% and + 27%; p ≤ 0.001), while parathormone (PTH) decreased significantly (from 36.6 to 34.4 pmol/L; % change - 11%, p = 0.03). CONCLUSIONS: Increasing dialysate magnesium improves vascular stiffness in subjects undergoing maintenance hemodialysis. The present findings merit a larger trial to evaluate the effects of 0.75 mmol/L D-Mg2+ on major clinical outcomes. TRIAL REGISTRATION: The study was retrospectively registered on the ISRCTN registry (ISRCTN 74139255) on 18 June 2020.