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.

Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed.

In hemodialysis patients extracellular fluid overload is a predictor of all-cause and cardiovascular mortality, and a relation with inflammation has been reported in previous studies. The magnitude and nature of this interaction and the effects of moderate fluid overload and extracellular fluid depletion on survival are still unclear. We present the results of an international cohort study in 8883 hemodialysis patients from the European MONDO initiative database where, during a three-month baseline period, fluid status was assessed using bioimpedance and inflammation by C-reactive protein. All-cause mortality was recorded during 12 months of follow up. In a second analysis a three-month baseline period was added to the first baseline period, and changes in fluid and inflammation status were related to all-cause mortality during six-month follow up. Both pre-dialysis estimated fluid overload and fluid depletion were associated with an increased mortality, already apparent at moderate levels of estimated pre-dialysis fluid overload (1.1-2.5L); hazard ratio 1.64 (95% confidence interval 1.35-1.98). In contrast, post-dialysis estimated fluid depletion was associated with a survival benefit (0.74 [0.62-0.90]). The concurrent presence of fluid overload and inflammation was associated with the highest risk of death. Thus, while pre-dialysis fluid overload was associated with inflammation, even in the absence of inflammation, fluid overload remained a significant risk factor for short-term mortality, even following improvement of fluid status.

Background and objectives High body mass index appears protective in hemodialysis patients, but uncertainty prevails regarding which components of body composition, fat or lean body mass, are primarily associated with survival. (FTIs), which are the respective tissue masses normalized to height squared, relative to an age-and sex-matched healthy population. The relationship between LTI and FTI and all-cause mortality was studied by Kaplan-Meier analysis, multivariate Cox regression, and smoothing spline ANOVA logistic regression.Results In 37,345 hemodialysis patients, median (25th-75th percentile) LTI and FTI were 12.2 (10.3-14.5) and 9.8 (6.6-12.4) kg/m 2 , respectively. Median (25th-75th percentile) follow-up time was 266 (132-379) days; 3458 (9.2%) patients died during follow-up. Mortality was lowest with both LTI and FTI in the 10th-90th percentile (reference group) and significantly higher at the lower LTI and FTI extreme (hazard ratio [HR], 3.37; 95% confidence interval [95% CI], 2.94 to 3.87; P,0.001). Survival was best with LTI between 15 and 20 kg/m 2 and FTI between 4 and 15 kg/m 2 (probability of death during follow-up: ,5%). When taking the relation between both compartments into account, the interaction was significant (P=0.01). Higher FTI appeared protective in patients with low LTI (HR, 3.37; 95% CI, 2.94 to 3.87; P,0.001 at low LTI-low FTI, decreasing to HR, 1.79; 95% CI, 1.47 to 2.17; P,0.001 at low LTI-high FTI).Conclusions This large international study indicates best survival in patients with both LTI and FTI in the 10th-90th percentiles of a healthy population. In analyses of body composition, both lean tissue and fat tissue compartments and also their relationship should be considered.

♦ Objective Hypertension, reduced arterial distensibility, and left ventricular hypertrophy (LVH) are risk factors for mortality in hemodialysis patients. However, few studies have focused on the relation between fluid status, blood pressure (BP), and cardiovascular abnormalities in peritoneal dialysis (PD) patients. This study was designed, first, to assess, using tracer dilution techniques, fluid status in PD patients compared to a control population of stable renal transplant (RTx) patients; second, to study the relation between fluid status, BP, and arterial wall abnormalities; third, to assess the determinants of cardiac structure; and last, to compare office and ambulatory BP measurements with respect to cardiac abnormalities. ♦ Design Cross-sectional study. ♦ Setting Multicenter study. ♦ Patients 41 stable PD patients with a mean Kt/V urea of 2.4 ± 0.7, and 77 stable RTx patients. ♦ Intervention Fluid status was assessed by tracer dilution techniques: extracellular volume (ECV) with bromide dilution; total body water (TBW) with deuterium oxide; and plasma volume (PV) with dextran 70. Echocardiography was performed to assess left ventricular mass (LVM), left ventricular end diastolic diameter (LVEDD), and relative wall thickness as indicators of LVH. Echography of the common carotid artery was performed to assess arterial distensibility. Both office and 24-hour ambulatory BP measurements were performed. ♦ Results Fluid status, as assessed by ECV corrected for body surface area (BSA) (ECV:BSA), was significantly different between PD and RTx patients (9.4 ± 2.6 vs 8.6 ± 1.2 L/m2, p < 0.05). In 36.6% of the PD patients, ECV:BSA was above the 90th percentile of the RTx patients. Fluid status corrected for BSA, assessed by TBW (TBW:BSA), ECV (ECV:BSA), or plasma volume (PV:BSA), was significantly related to diastolic BP (DBP) ( r = 0.35, r = 0.37, r = 0.53; p < 0.05). Arterial distensibility of the common carotid artery was related to systolic BP (SBP) ( r = –0.36, p < 0.05). ECV was significantly related to LVEDD ( r = 0.41, p < 0.05) as a marker of eccentric LVH, whereas arterial distensibility was related to relative wall thickness ( r = –0.53, p < 0.001) as a marker of concentric LVH. An abnormal day–night BP rhythm, which was not related to fluid status, was observed in 68.4% of patients. Ambulatory DBP and SBP but not office DBP and SBP were related to LVM ( r = 0.43, r = 0.46; p < 0.01). ♦ Conclusions A large proportion of PD patients whose treatment prescriptions are in accordance with the Dialysis Outcomes Quality Initiative guidelines were found to be overhydrated compared with a population of stable RTx patients. Fluid status was significantly related to DBP and eccentric LVH, whereas arterial distensibility of the common carotid artery was significantly related to SBP and concentric LVH. In contrast to ambulatory BP, office BP was not related to LVM.

In HD patients, hyponatremia is associated with malnutrition, inflammation and fluid overload. Hyponatremia maintained predictive for all-cause mortality after adjustment for malnutrition, inflammation and fluid status abnormalities. The presence of hyponatremia may assist in identifying HD patients at increased risk of death.

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In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFR was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals.