A Pilot Observational Study Assessing Long-Term Changes in Clinical Parameters, Functional Capacity and Fall Risk of Patients With Chronic Renal Disease Scheduled for Hemodialysis

Background: Patients with end-stage renal disease are known to be particularly frail, and the cause is still widely seen as being directly related to specific factors in renal replacement therapy. However, a closer examination of the transitional phase from predialysis to long-term hemodialysis leads to controversial explanations, considering that the frailty process is already well-described in the early stages of renal insufficiency. This study aims to describe longitudinally and multifactorially changes in the period extending from the decision to start the replacement therapy through to the end of 2 years of hemodialysis. We hypothesized that frailty is pre-existent in the predialysis phase and does not worsen with the beginning of the replacement therapy. Between 2015 and 2018 we recruited 25 patients (72.3 ± 5.7 years old) in a predialysis program, with the expectation that replacement therapy would begin within the coming few months. Methods: The patients underwent a baseline visit before starting hemodialysis, with 4 follow-up visits in the first 2 years of treatment. Health status, physical performance, cognitive functioning, hematology parameters, and adverse events were monitored during the study period. Results: At baseline, our sample had a high variability with patients ranging from extremely frail to very fit. In the 14 participants that did not drop out of the study, out of 32 clinical and functional measures, a statistically significant worsening was only observed in the Short Physical Performance Battery (SPPB) score (p < 0.01, F = 8.50) and the number of comorbidities (p = 0.01, F = 3.94). A careful analysis, however, reveals a quite stable situation in the first year of replacement therapy, for both frail and fit participants and a deterioration in the second year that in frail participants could lead to death. Conclusion: Our results should stimulate a reassessment about the role of a predialysis program in reducing complications during the transitional phase, but also about frailty prevention programs once hemodialysis has begun, for both frail and fit patients, to maintain satisfactory health status.ISSN:2296-858

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

Funder: Swiss Kidney FoundationPatients 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