Dialysis patients and kidney transplant (KTX) recipients suffer from an impaired immune system and show a decreased response to the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination. We performed a retrospective analysis of 1505 serological SARS-CoV-2 measurements obtained from 887 dialysis patients and 86 KTX recipients. The results were separated by patient subgroups (dialysis/KTX) as well as SARS-CoV-2 status. The latter criterion included SARS-CoV-2-naïve patients with or without COVID-19 vaccination and convalescent patients receiving a booster shot. Serologies of 27 vaccinated healthy individuals served as the reference group. Vaccine-induced cellular immune response was quantified by an interferon-γ release assay in 32 KTX recipients. We determined seroconversion rates of 92.6%, 93.4%, and 71.4% in dialysis patients vaccinated with either BNT162b2, mRNA-1273, or AZD1222, respectively. Vaccination-induced anti-SARS-CoV-2 antibody titers were lower in dialysis patients compared to healthy individuals, and vaccination with mRNA-1273 induced higher titers than BNT162b2. The initial seroconversion rate was 39.5% in KTX recipients vaccinated with BNT162b2. A linear regression model identified medication with mycophenolate-mofetil/mycophenolic acid as an independent risk factor for missing seroconversion. Within a cohort of 32 KTX recipients, cellular and humoral immune reactivity to SARS-CoV-2 was detectable in three patients only. Conclusively, vaccine-induced seroconversion rates were similar in dialysis patients compared to healthy individuals but were strongly impaired in KTX recipients. Anti-SARS-CoV-2 IgG titers elicited by double active immunization were significantly lower in both cohorts compared to healthy individuals, and immune responses to vaccination vanished quickly.
Background Ketogenic dietary interventions (KDI) have been shown to be effective in animal models of polycystic kidney disease, but data from clinical trials are lacking. Methods Ten ADPKD patients with rapid disease progression were enrolled at visit V1 and initially maintained a carbohydrate (CHO)-rich diet. At V2, patients entered one of the two KDI arms: a 3-day water fast (WF) or a 14-day ketogenic diet (KD). At V3, they resumed their normal diet for 3 to 6 weeks until V4. At each visit, MRI kidney and liver volumetry was performed. Ketone bodies were evaluated to assess metabolic efficacy and questionnaires were used to determine feasibility. Results All participants (KD n = 5, WF n = 5; age 39.8 ± 11.6 years; eGFR 82 ± 23.5 ml/min; total kidney volume (TKV) 2224 ± 1156 ml) were classified as Mayo Class 1C to 1E. Acetone levels in breath and BHB blood levels increased in both study arms (V1 to V2 average acetone: 2.7±1.2 ppm, V2 to V3: 22.8±11.9 ppm, p = 0.0006; V1 to V2 average BHB: 0.22±0.08 mmol/l, V2 to V3: 1.88±0.93 mmol/l, p = 0.0008). 9/10 patients reached a ketogenic state and 9/10 evaluated KDIs as feasible. TKV did not change during this trial. However, we found a significant impact on total liver volume (ΔTLV V2 to V3: -7.7%, p = 0.01), mediated by changes in its non-cystic fraction. Conclusions RESET-PKD demonstrates that short-term KDIs potently induce ketogenesis and are feasible for ADPKD patients in daily life. While TLV quickly changed upon the onset of ketogenesis, changes in TKV may require longer-term interventions.
Background Our laboratory published the first evidence that nutritional ketosis, induced by ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in PKD animal models. We reasoned that, due to their frequent use for numerous health benefits, some ADPKD patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect first real-life observations of ADPKD patients about safety, feasibility, and possible benefits of KDIs in ADPKD as part of a translational project pipeline. Methods Patients with ADPKD who had already used KDIs were recruited to retrospectively collect observational and medical data about beneficial or adverse effects, the feasibility and safety of KDIs in questionnaire-based interviews. Results 131 ADPKD patients took part in this study. 74 executed a KD and 52 TRD, for 6 months on average. 86% of participants reported that KDIs had improved their overall health. 67% described improvements in ADPKD-associated health issues. 90% observed significant weight loss. 64% of participants with hypertension reported improvements in blood pressure. 66% noticed adverse effects that are frequently observed with KDIs. 22 participants reported safety concerns like hyperlipidemia. 45 participants reported slight improvements in eGFR. 92% experienced KDIs as feasible while 53% reported breaks during their diet. Discussion Our preliminary data indicate that KDIs may be safe, feasible, and potentially beneficial for ADPKD patients highlighting that prospective clinical trials are warranted to confirm these results in a controlled setting and elucidate the impact of KDIs specifically on kidney function and cyst progression.
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