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Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care.

Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research.

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8–6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis.

Background: Patients on kidney replacement therapy (KRT) are at very high risk of coronavirus disease 2019 (COVID-19). The triage pathway for KRT patients presenting to hospitals with varying severity of COVID-19 illness remains ill-defined. We studied the clinical characteristics of patients at initial and subsequent hospital presentations and the impact on patient outcomes. Methods: The 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 at initial triage and those re-presenting a second time. Predictors of outcomes (hospitalization, 28-day mortality) were then determined for all those not hospitalized at initial triage. Results: Among 1423 KRT patients with COVID-19 [haemodialysis (HD), n = 1017; transplant, n = 406), 25% (n = 355) were not hospitalized at first presentation due to mild illness (30% HD, 13% transplant). Of the non-hospitalized patients, only 10% (n = 36) re-presented a second time, with a 5-day median interval between the two presentations (interquartile range 2-7 days). Patients who re-presented had worsening respiratory symptoms, a decrease in oxygen saturation (97% versus 90%) and an increase in C-reactive protein (26 versus 73 mg/L) and were older (72 vs 63 years) compared with those who did not return a second time. The 28-day mortality between early admission (at first presentation) and deferred admission (at second presentation) was not significantly different (29% versus 25%; P = 0.6). Older age, prior smoking history, higher clinical frailty score and self-reported shortness of breath at first presentation were identified as risk predictors of mortality when re-presenting after discharge at initial triage. Conclusions: This study provides evidence that KRT patients with COVID-19 and mild illness can be managed effectively with supported outpatient care and with vigilance of respiratory symptoms, especially in

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 6 13 and 67 6 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 ¼ 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n ¼ 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