Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation <1 year before presentation (HR adjusted for sex, age and frailty 0.20, 95% CI 0.07–0.56, P < 0.01). Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Background COVID-19 has exposed hemodialysis patients and kidney transplant recipients to an unprecedented life-threatening infectious disease raising concerns about kidney replacement therapy (KRT) strategy during the pandemic. The present study investigated the association of type of KRT with COVID-19 severity adjusting for differences in individual characteristics. Methods Data on kidney transplant recipients and hemodialysis patients diagnosed with COVID-19 between February 1st and December 1st 2020 were retrieved from ERACODA. Cox regression models adjusted for age, sex, frailty and comorbidities were used to estimate hazard ratios (HR) for 28-day mortality risk in all patients and in the subsets who were tested because of symptoms Results In total, 1,670 patients (496 functional kidney transplant and 1,174 hemodialysis) were included. 16.9% of kidney transplant and 23.9% of hemodialysis patients died within 28 days of presentation. The unadjusted 28-day mortality risk was 33% lower in kidney transplant recipients compared with hemodialysis patients (HR: 0.67, 95%CI: 0.52-0.85). In a fully adjusted model, the risk was 78% higher in kidney transplant recipients (HR: 1.78, 95%CI: 1.22-2.61) compared with hemodialysis patients. This association was similar in patients tested because of symptoms (fully adjusted model HR: 2.00, 95%CI: 1.31-3.06). This risk was dramatically increased during the first post-transplant year. Results were similar for other endpoints (e.g. hospitalization, ICU admission, mortality beyond 28 days) and across subgroups. Conclusions Kidney transplant recipients had a greater risk of a more severe course of COVID-19 compared with hemodialysis patients; they therefore require specific infection mitigation strategies.

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α-Klotho is an interesting new biomarker in kidney and cardiovascular disease. As α-Klotho is primarily expressed in renal epithelial tissue, various papers have reported α-Klotho concentrations in urine. As these studies did not address the reliability of urinary α-Klotho measurements and as urine is known to be a complex milieu, we investigated the stability of α-Klotho in both fresh catheter and fresh voided urine. α-Klotho was measured in these fresh urine samples and in the same samples under several other conditions. Storage of fresh catheter urine for 3 h at 37 °C, comparable to storage in the bladder, led to a 82% decrease in α-Klotho concentrations. Compared with fresh voided urine, α-Klotho concentrations decreased on an average of 45 and 82% after storage at -80 °C and -20 °C, respectively. An additional freeze-thaw cycle further decreased α-Klotho concentrations. The addition of a protease inhibitor or 0.1% albumin partly prevented degradation in fresh voided urine. Thus, α-Klotho is highly unstable in urine. Future studies showing results of urinary α-Klotho should mention conservation conditions and prove the reliability of the α-Klotho measurements.

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Background: Increased levels of phosphate and fibroblast growth factor-23 (FGF23) are strong predictors of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Preliminary data suggest that interventions lowering gastro-intestinal phosphate uptake lowers serum FGF23 concentrations and improves cardiovascular risk and subsequently survival. However, data are lacking about the magnitude of effects, the effect in different stages of CKD and whether there is a dose-effect relationship. Methods: Therefore, the Sevelamer on FGF23 Trial (SoFT) is designed as an open-label, single-arm, clinical pilot study aiming to demonstrate the feasibility of a phosphate-restricted diet in combination with the phosphate binder sevelamer to induce an effective, predictable and sustained decrease in FGF23 level in patients with an estimated glomerular filtration rate (eGFR) of 15-90 or >90 ml/min/1.73 m² with proteinuria >1.0 g in 24 h urine collection, despite optimally dosed RAAS blockade, without inducing hypophosphatemia using a forced uptitration treatment regimen aimed at restricting phosphate uptake.

The CKD-associated decline in soluble α-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti-oxidant therapy can upregulate the expression of α-Klotho in the kidney. We examined the effect of anti-oxidant therapy on α-Klotho concentrations in a clinical cohort with mild tot moderate chronic kidney disease (CKD). We performed a post-hoc analysis of a prospective randomized trial involving 62 patients with mild to moderate CKD (the ATIC study), all using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for 12 months. On top of that, the intervention group received anti-oxidative therapy consisting of the combination of pravastatin (40 mg/d) and vitamin E (α-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. α-Klotho concentrations were measured at baseline and after 12 months of anti-oxidant therapy. Data were analysed using T-tests and Generalized Estimating Equations, adjusting for potential confounders such as vitamin D, parathyroid hormone, fibroblast-growth-factor 23 (FGF23) and eGFR. The cohort existed of 62 patients with an eGFR (MDRD) of 35 ± 14 ml/min/1.72m2, 34 were male and mean age was 53.0 ± 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P <0.001). α-Klotho concentrations did not change in patients receiving either anti-oxidative therapy (476.9 ± 124.3 to 492.7 ± 126.3 pg/mL, P = 0.23) nor in those receiving placebo 483.2 ± 142.5 to 489.6 ± 120.3 pg/mL, P = 0.62). Changes in α-Klotho concentrations were not different between both groups (p = 0.62). No evidence was found that anti-oxidative therapy affected α-Klotho concentrations in patients with mild-moderate CKD.

Rationale & Objective Patients on kidney replacement therapy (KRT) are at a very high risk of COVID-19. Triage pathway for KRT patients presenting with varying severity of COVID-19 illness remains ill-defined. We studied clinical characteristics of patients at initial and subsequent hospital presentations and its impact on patient outcomes. Study Design, Setting, Participants European Renal Association COVID-19 Database (ERACODA) was analysed for clinical and laboratory features of 1423 KRT patients with COVID-19 either hospitalized or non-hospitalized during first presentation and those representing after non-admission at initial triage. Predictors of outcomes (Hospitalisation, 28-day mortality) were determined for those not hospitalized at first presentation. Results Amongst 1423 KRT patients with COVID-19 (Hemodialysis = 1017/Transplant = 406), 25% (n = 355) were not hospitalized at first presentation (30% Hemodialysis/13% Transplant). Of these non-hospitalized patients, 10% (n = 36) re-presented second time, with a 5-day median interval between two presentations (Interquartile interval 2-7 days). Patients who re-presented had worsening respiratory symptoms, a fall in oxygen saturation (97% vs. 90%) and rise in C-reactive protein between attendances (26 vs. 73 mg/L). Patients on second presentation were older (72 vs. 63 years), had early respiratory symptoms and lung imaging abnormalities compared with those who did not return second time. The 28-day mortality for those admitted at first or second presentations was not significantly different (25% vs. 29%, p = 0.6). Higher age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation, were identified as predictors of mortality in those discharged at initial triage. Conclusions The study provides evidence that KRT patients with COVID-19 and mild pulmonary abnormalities with lack of pulmonary insufficiency can be safely discharged, with vigilance of respiratory symptoms, especially in those with risk factors for poor outcomes. Our findings support a risk-stratified clinical approach to admissions and discharges of KRT patients presenting with COVID-19, to aid clinical triage and optimise resource utilisation during the ongoing pandemic.