Background: COVID-19 is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD) stages G4-G5, on dialysis or after kidney transplantation (kidney replacement therapy, KRT). SARS-CoV-2 vaccine trials do not elucidate if SARS-CoV-2 vaccination is effective in these patients. Vaccination against other viruses is known to be less effective in kidney patients. Our objective is to assess the efficacy and safety of various types of SARS-CoV-2 vaccinations in patients with CKD stages G4-G5 or on KRT. Methods: In this national prospective observational cohort study we will follow patients with CKD stages G4-G5 or on KRT (n = 12,000) after SARS-CoV-2 vaccination according to the Dutch vaccination program. Blood will be drawn for antibody response measurements at day 28 and month 6 after completion of vaccination. Patient characteristics and outcomes will be extracted from registration data and questionnaires during 2 years of follow-up. Results will be compared with a control group of non-vaccinated patients. The level of antibody response to vaccination will be assessed in subgroups to predict protection against COVID-19 breakthrough infection. Results: The primary endpoint is efficacy of SARS-CoV-2 vaccination determined as the incidence of COVID-19 after vaccination. Secondary endpoints are the antibody based immune response at 28 days after vaccination, the durability of this response at 6 months after vaccination, mortality and (serious) adverse events. Conclusion: This study will fulfil the lack of knowledge on efficacy and safety of SARS-CoV-2 vaccination in patients with CKD stages G4-G5 or on KRT. Trial registration: The study protocol has been registered in clinicaltrials.gov(NCT04841785). Current knowledge about this subject COVID-19 has devastating impact on patients with CKD stages G4-G5, on dialysis or after kidney transplantation. Effective SARS-CoV-2 vaccination is very important in these vulnerable patient groups. Recent studies on vaccination in these patient groups are small short-term studies with surrogate endpoints. Contribution of this study Assessment of incidence and course of COVID-19 after various types of SARS-CoV-2 vaccination during a two-year follow-up period in not only patients on dialysis or kidney transplant recipients, but also in patients with CKD stages G4-G5. Quantitative analysis of antibody response after SARS-CoV-2 vaccination and its relationship with incidence and course of COVID-19 in patients with CKD stages G4-G5, on dialysis or after kidney transplantation compared with a control group. Monitoring of (serious) adverse events and development of anti-HLA antibodies. Impact on practice or policy Publication of the study design contributes to harmonization of SARS-CoV-2 vaccine study methodology in kidney patients at high-risk for severe COVID-19. Data on efficacy of SARS-CoV-2 vaccination in patients with CKD will provide guidance for future vaccination policy.

The burden of post COVID-19 condition (PCC) is not well studied in patients with advanced kidney disease. A large prospective cohort of SARS-CoV-2 vaccinated patients with chronic kidney disease stages G4-G5 (CKD G4/5), on dialysis, and kidney transplant recipients (KTR) were included. Antibody levels were determined after vaccination. Presence of long-lasting symptoms was assessed in patients with and without prior COVID-19 and compared using logistic regression. In patients with prior COVID-19, PCC was defined according to the WHO definition. 216 CKD G4/5 patients, 375 dialysis patients, and 2005 KTR were included. Long-lasting symptoms were reported in 204/853 (24%) patients with prior COVID-19 and in 297/1743 (17%) patients without prior COVID-19 (aOR: 1.45 (1.17-1.78)], p<0.001). PCC was prevalent in 29% of CKD G4/5 patients, 21% of dialysis patients, and 24% of KTR. In addition, 69% of patients with PCC reported (very) high symptom burden. Odds of PCC was lower per ten-fold increase in antibody level after vaccination (aOR 0.82 [0.70-0.96], p=0.01) and higher in case of COVID-19 related hospital admission (aOR 4.64 [2.61-8.25], p=0.003). CKD G4/5 patients, dialysis patients, and KTR are at risk for PCC with high symptom burden after SARS-CoV-2 vaccination, especially if antibody levels are low and in case of hospitalization due to COVID-19.

Patients with chronic kidney disease or kidney replacement therapy demonstrate lower antibody levels after SARS-CoV-2 vaccination compared to healthy controls. In a prospective cohort, we analysed the impact of immunosuppressive treatment and type of vaccine on antibody levels after three SARS-CoV-2 vaccinations. Control subjects (n = 186), patients with CKD G4/5 (n = 400), dialysis patients (n = 480) and kidney transplant recipients (KTR) (n = 2468) were vaccinated with either mRNA-1273 (Moderna), BNT162b2 (Pfizer-BioNTech) or AZD1222 (Oxford/AstraZeneca) in the Dutch SARS-CoV-2 vaccination programme. Third vaccination data were available in a subgroup of patients (n = 1829). Blood samples and questionnaires were obtained one month after the second and third vaccination. Primary endpoint was the antibody level in relation to immunosuppressive treatment and type of vaccine. Secondary endpoint was occurrence of adverse events after vaccination. Antibody levels after two and three vaccinations were lower in patients with CKD G4/5 and dialysis patients with immunosuppressive treatment compared to patients without immunosuppressive treatment. After two vaccinations, we observed lower antibody levels in KTR using mycophenolate mofetil (MMF) compared to KTR not using MMF (20 BAU/ml [3–113] versus 340 BAU/ml [50–1492], P < 0.001). Seroconversion was observed in 35% of KTR using MMF, compared to 75% of KTR not using MMF. Of the KTR who used MMF and did not seroconvert, eventually 45% seroconverted after a third vaccination. mRNA-1273 induces higher antibody levels as well as a higher frequency of adverse events compared to BNT162b2 in all patient groups. Immunosuppressive treatment adversely affects the antibody levels after SARS-CoV-2 vaccination in patients with CKD G4/5, dialysis patients and KTR. mRNA-1273 vaccine induces a higher antibody level and higher frequency of adverse events.

Background: The European Kidney Function Consortium (EKFC) 2021 equation to estimate GFR performs as well or better than the CKD-EPI 2009 equation in predominantly White adult European populations, with less bias and greater accuracy against measured GFR. This study explores how changing from the CKD-EPI to the EKFC equation in a large European health system may affect disease distribution, prognosis, and clinical decisions. Methods: We studied >1.7 million adults in Stockholm undergoing routine care during 2006–2021. We compared eGFR values and reclassification across KDIGO GFR categories when changing from the CKD-EPI to EKFC equation and examined associations of eGFR and reclassification with risk for kidney failure with replacement therapy (KFRT), mortality, and major adverse cardiovascular events (MACE) using Cox models. We also modeled the impact of eGFR equation change on clinical decisions such as nephrology referral or medication eligibility/contraindication. Results: EKFC yielded modestly lower eGFR values than CKD-EPI by a median (IQR) of −4.9 (−8.3 to −2.2) ml/min/1.73 m². As a result, CKD G3–G5 prevalence rose from 4.5% to 6.2%. Both equations strongly predicted KFRT, mortality, and MACE. Participants reclassified to lower eGFR categories were older; after adjustment for age, participants had similar risks of mortality and MACE to those not reclassified and a lower risk of KFRT. Changing to the EKFC equation would impact clinical decisions at low eGFR thresholds, such as nephrology referrals (22% higher), eligibility for SGLT2 is (39% higher), or contraindication for spironolactone in heart failure (26% higher). Conclusions: Adopting the EKFC equation in this Northern European health system would modestly lower eGFR estimates, increasing the prevalence of moderate/severe CKD and affecting clinical classification and decisions. eGFR by both equations strongly predicted outcomes, but individuals reclassified to a lower eGFR category by EKFC did not have consistent associations across outcomes.

Despite (repeated) boosting, kidney transplant recipients (KTRs) may remain at increased risk of severe COVID‐19 since a substantial number of individuals remain seronegative or with low antibody titers. In particular, mycophenolic acid use has been shown to affect antibody formation negatively and may be an important modifiable risk factor. We investigated the exposure–response relationship between mycophenolic acid 12‐hour area under the curve (AUC_0–12h) exposure and seroconversion including antibody titers after vaccination using mRNA‐1273 SARS‐CoV‐2 vaccine (Moderna) in 316 KTRs from our center that participated in the national Dutch renal patients COVID‐19 vaccination – long term efficacy and safety of SARS‐CoV‐2 vaccination in kidney disease patients vaccination study. After two vaccination doses, 162 (51%) KTRs seroconverted. KTRs treated with mycophenolic acid showed less seroconversion and lower antibody titers compared with KTRs without mycophenolic acid (44% vs. 77%, and 36 binding antibody units (BAU)/mL vs. 340 BAU/mL; P < 0.001). The mean mycophenolic acid AUC_0–12h exposure was significantly lower in KTRs who seroconverted compared with KTRs who did not (39 vs. 29 mg⋅h/L; P < 0.001). High mycophenolic acid exposure (±90 mg⋅h/L) and no exposure to mycophenolic acid resulted in a seroconversion rate ranging from 10% to 80%. Every 10 mg⋅h/L increase in mycophenolic acid AUC_0–12h gave an adjusted odds ratio for seroconversion of 0.87 (95% confidence interval (CI), 0.79–0.97; P = 0.010) and 0.89 (95% CI, 0.85–0.93; P < 0.001) for KTRs on dual and triple maintenance immunosuppressive therapy, respectively. Higher mycophenolic acid AUC_0–12h correlated with lower antibody titers (R = 0.44, P < 0.001). This study demonstrates the exposure–response relationship between gold standard mycophenolic acid exposure and antibody formation to support interventional studies investigating mycophenolic acid adjustment to improve antibody formation after further boosting.

Background: Several guidelines recommend using the Clinical Frailty Scale (CFS) for triage of critically ill coronavirus disease 2019 (COVID-19) patients. This study evaluates the impact of CFS on intensive care unit (ICU) admission rate and hospital and ICU mortality rates in hospitalized dialysis patients with COVID-19.Methods: We analysed data of dialysis patients diagnosed with COVID-19 from the European Renal Association COVID-19 Database. The primary outcome was ICU admission rate and secondary outcomes were hospital and ICU mortality until 3 months after COVID-19 diagnosis. Cox regression analyses were performed to assess associations between CFS and outcomes.Results: A total of 1501 dialysis patients were hospitalized due to COVID-19, of whom 219 (15%) were admitted to an ICU. The ICU admission rate was lowest (5%) in patients >75 years of age with a CFS of 7–9 and highest (27%) in patients 65–75 years of age with a CFS of 5. A CFS of 7–9 was associated with a lower ICU admission rate than a CFS of 1–3 [relative risk 0.49 (95% confidence interval 0.27–0.87)]. Overall, mortality at 3 months was 34% in hospitalized patients, 65% in ICU-admitted patients and highest in patients >75 years of age with a CFS of 7–9 (69%). Only 9% of patients with a CFS ≥6 survived after ICU admission. After adjustment for age and sex, each CFS category ≥4 was associated with higher hospital and ICU mortality compared with a CFS of 1–3.Conclusions: Frail dialysis patients with COVID-19 were less frequently admitted to the ICU. Large differences in mortality rates between fit and frail patients suggest that the CFS may be a useful complementary triage tool for ICU admission in dialysis patients with COVID-19.