Rapamycin ameliorates proteinuria and restores nephrin and podocin expression in experimental membranous nephropathy.

OBJECTIVE: Recent studies have shown a beneficial effect of rapamycin in passive and active Heymann Nephritis (HN). However, the mechanisms underlying this beneficial effect have not been elucidated. METHODS: Passive Heymann Nephritis (PHN) was induced by a single intravenous infusion of anti-Fx1 in 12 Sprague-Dawley male rats. One week later, six of these rats were commenced on daily treatment with subcutaneous rapamycin 0.5 mgr/kg (PHN-Rapa). The remaining six rats were used as the proteinuric control group (PHN) while six more rats without PHN were given the rapamycin solvent and served as the healthy control group (HC). All rats were sacrificed at the end of the 7th week. RESULTS: Rapamycin significantly reduced proteinuria during the autologous phase of PHN. Histological lesions were markedly improved by rapamycin. Immunofluorescence revealed attenuated deposits of autologous alloantibodies in treated rats. Untreated rats showed decreased glomerular content of both nephrin and podocin whereas rapamycin restored their expression. CONCLUSIONS: Rapamycin monotherapy significantly improves proteinuria and histological lesions in experimental membranous nephropathy. This beneficial effect may be mediated by inhibition of the alloimmune response during the autologous phase of PHN and by restoration of the normal expression of the podocyte proteins nephrin and podocin.

Dialysis Patients Respond Adequately to Influenza Vaccination Irrespective of Dialysis Modality and Chronic Inflammation.

(1) Background: Chronic inflammation and suboptimal immune responses to vaccinations are considered to be aspects of immune dysregulation in patients that are undergoing dialysis. The present study aimed to evaluate immune responses in hemodialysis (HD) and online hemodiafiltration (OL-HDF) patients to a seasonal inactivated quadrivalent influenza vaccine (IQIV). (2) Methods: We enrolled 172 chronic dialysis patients (87 on HD and 85 on OL-HDF) and 18 control subjects without chronic kidney disease in a prospective, cross-sectional cohort study. Participants were vaccinated with a seasonal IQIV, and antibody titers using the hemagglutination inhibition (HI) assay were determined before vaccination (month 0) and 1, 3, and 6 months thereafter. Demographics and inflammatory markers (CRP, IL-6, IL-1ß) were recorded at month 0. The primary endpoints were the rates of seroresponse (SR), defined as a four-fold increase in the HI titer, and seroprotection (SP), defined as HI titer ≥ 1/40 throughout the study period. Statistical analyses were conducted in R (version 3.6.3) statistical software. The differences between groups were analyzed using chi-square and t-test analyses for dichotomous and continuous variables, respectively. To identify independent determinants of SR and SP, generalized linear models were built with response or protection per virus strain as the dependent variable and group, age, sex, time (month 0, 1, 3, 6), diabetes, IL-6, dialysis vintage, HD access, and HDF volume as independent explanatory variables. (3) Results: SR and SP rates were similar between control subjects, and dialysis patients were not affected by dialysis modality. SP rates were high (> 70%) at the beginning of the study and practically reached 100% after vaccination in all study groups. These results applied to all four virus strains that were included in the IQIV. IL-6 levels significantly differed between study groups, with HD patients displaying the highest values, but this did not affect SP rates. (4) Conclusions: Dialysis patients respond to influenza immunization adequately and similarly to the general population. Thus, annual vaccination policies should be encouraged in dialysis units. OL-HDF reduces chronic inflammation; however, this has no impact on SR rates.