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Hemodialysis patients (HD) are expected to have excess mortality in coronavirus disease 2019 (COVID-19). This was challenged by a recent study reporting HD patients to have comparable mortality and less ICU admissions when hospitalized with COVID-19. An altered immune system due to chronic inflammation might protect HD-patients from severe COVID-19. Therefore, we aimed to describe the peripheral blood immune phenotype in HD-patients and respective controls with COVID-19.

Background Because chronic fluid volume overload is associated with higher mortality, we tested whether blood-volume monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) would facilitate dry weight reduction, in comparison to conventional dialysis (CONV). Methods We carried out a multicenter, 4-week, randomized controlled trial in hemodialysis patients ≥15% above normal extracellular fluid volume (ECV), per bioimpedance spectroscopy, who were randomized 1:1:1. Applying UCR (Nikkiso), UTR (Fresenius) and CONV, initial dry weight was reduced rapidly to target. Dry weight reduction was attenuated and eventually stopped at the occurrence of dialysis complications. The primary outcome was defined as intra- and postdialytic complications. Secondary outcomes were magnitudes of dry weight and blood pressure reduction. Results Of 244 patients assessed, N  = 95 had volume overload ≥15% above normal ECV. Fifty patients received the allocated interventions ( N  = 16 UCR, N  = 18 UTR, N  = 16 CONV) and completed the trial. The rate of complications was significantly lower in UTR compared to CONV (21 ± 21% vs 34 ± 20%, p  = 0.022), and also compared to UCR (vs 39 ± 27%, p  = 0.028), but not statistically different between UCR and CONV ( p  = 0.93). Dry weight reduction was significantly higher in UTR compared to UCR (5.0 ± 3.4% vs 2.0 ± 2.7% body weight, p  = 0.013), but not compared to CONV (vs 3.9 ± 2.1% body weight, p  = 0.31). Systolic blood pressure reduction throughout the intervention phase was 17 ± 22 mmHg overall, but not significantly different between the three groups. Average maximum ultrafiltration rates were significantly higher in UTR than in UCR and CONV, at statistically similar dialysis times. Retrospective examination of randomly selected hemodialysis sessions in the UCR group identified technical mistakes in 36% of the dialysis sessions, despite considerable training efforts. Conclusions Even in patients with volume overload, fluid removal was challenging. Despite the relative advantage of UTR, which must be interpreted with caution in view of the poor technical execution of UCR, this study renders clear that fluid removal must not be reinforced rapidly. Apprehension of this obstacle is imperative for future clinical and academic endeavors aimed at improving dialysis outcomes by correcting volume status. Trial registration ClinicalTrials.gov ( NCT01416753 ), trial registration date: August 12, 2011.

Background: We evaluated whether cell-free plasma DNA might be an appropriate marker for cell damage during hemodialysis (HD) and whether it correlated with annexin V expression and 7-amino-actinomycin D (7AAD) nuclear staining of blood leukocytes. Methods: Circulating DNA, annexin V, and 7AAD were measured in HD patients before HD, 20 min after start of HD, and after HD had ended. Healthy volunteers provided control measurements. Necrosis and apoptosis were monitored by gel electrophoresis. Results: Plasma DNA concentrations were not significantly different between controls and patients before HD. Circulating DNA increased significantly (P <0.05) after 20 min of treatment with HD. Post-HD concentrations of DNA were significantly higher compared with pre-HD and controls (P <0.005). Agarose gel electrophoresis showed ladders typical of apoptosis in post-HD samples. Two subpopulations of CD45+ leukocytes were defined by flow cytometry: annexin V+/7AAD+ population for apoptosis, and annexin V+/7AAD− for early apoptosis. Compared with healthy controls, mean fluorescence (MF) of 7AAD+ apoptotic cells in the annexin V+/7AAD+ subpopulation before HD was not significantly increased. HD increased MF of 7AAD+ cells in the annexin V+/7AAD+ subpopulation. In this subpopulation, MF of annexin V+ cells was significantly higher (P <0.01). MF of annexin V+ cells in the annexin V+/7AAD+ subpopulation increased during HD. Conclusions: During HD, cell-free plasma DNA concentrations, annexin V expression, and 7AAD uptake in leukocytes increases. The increase in plasma DNA, appearing as ladders typical of apoptosis, and the 7AAD uptake in leukocytes demonstrate that the predominant portion of circulating DNA in HD patients originates from apoptotic leukocytes.

Background Data generated with the body composition monitor (BCM, Fresenius) show, based on bioimpedance technology, that chronic fluid overload in hemodialysis patients is associated with poor survival. However, removing excess fluid by lowering dry weight can be accompanied by intradialytic and postdialytic complications. Here, we aim at testing the hypothesis that, in comparison to conventional hemodialysis, blood volume-monitored regulation of ultrafiltration and dialysate conductivity (UCR) and/or regulation of ultrafiltration and temperature (UTR) will decrease complications when ultrafiltration volumes are systematically increased in fluid-overloaded hemodialysis patients. Methods/design BCM measurements yield results on fluid overload (in liters), relative to extracellular water (ECW). In this prospective, multicenter, triple-arm, parallel-group, crossover, randomized, controlled clinical trial, we use BCM measurements, routinely introduced in our three maintenance hemodialysis centers shortly prior to the start of the study, to recruit sixty hemodialysis patients with fluid overload (defined as ≥15% ECW). Patients are randomized 1:1:1 into UCR, UTR and conventional hemodialysis groups. BCM-determined, ‘final’ dry weight is set to normohydration weight −7% of ECW postdialysis, and reached by reducing the previous dry weight, in steps of 0.1 kg per 10 kg body weight, during 12 hemodialysis sessions (one study phase). In case of intradialytic complications, dry weight reduction is decreased, according to a prespecified algorithm. A comparison of intra- and post-dialytic complications among study groups constitutes the primary endpoint. In addition, we will assess relative weight reduction, changes in residual renal function, quality of life measures, and predialysis levels of various laboratory parameters including C-reactive protein, troponin T, and N-terminal pro-B-type natriuretic peptide, before and after the first study phase (secondary outcome parameters). Discussion Patients are not requested to revert to their initial degree of fluid overload after each study phase. Therefore, the crossover design of the present study merely serves the purpose of secondary endpoint evaluation, for example to determine patient choice of treatment modality. Previous studies on blood volume monitoring have yielded inconsistent results. Since we include only patients with BCM-determined fluid overload, we expect a benefit for all study participants, due to strict fluid management, which decreases the mortality risk of hemodialysis patients. Trial registration ClinicalTrials.gov, NCT01416753

Abstract Introduction Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce cardiovascular events across a wide range of kidney function, including advanced stages of chronic kidney disease, but evidence for their efficacy in patients with kidney failure on haemodialysis is lacking. The underlying mechanisms remain incompletely understood, and whether cardiovascular benefits depend on residual kidney function is unknown. Study design The Dapagliflozin in Hemodialysis (DAPA-HD) trial (NCT05179668) is an academic, multicentre, randomized, double-blind, placebo-controlled trial designed to assess the cardiovascular effects of dapagliflozin in 220 patients with kidney failure receiving haemodialysis. Stratified block randomization was based on patient-reported residual urine volume. The primary endpoint is the change in left ventricular mass indexed to body surface area using echocardiography after 6 months of treatment. A prespecified subgroup analysis will compare treatment effects between patients with residual urine output >200 ml/24 h versus ≤200 ml/24 h. Secondary endpoints include additional echocardiographic assessments, changes in biomarker concentrations, quality of life, and clinical events. Discussion The DAPA-HD trial is the first trial specifically evaluating the cardiovascular and haemodynamic effects of dapagliflozin in patients with kidney failure receiving maintenance haemodialysis with and without residual urine outputs.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce cardiovascular events across a wide range of kidney function, including advanced stages of chronic kidney disease, but evidence for their efficacy in patients with kidney failure on hemodialysis is lacking. The underlying mechanisms remain incompletely understood, and whether cardiovascular benefits depend on residual kidney function is unknown.BACKGROUNDSodium-glucose co-transporter 2 inhibitors (SGLT2i) reduce cardiovascular events across a wide range of kidney function, including advanced stages of chronic kidney disease, but evidence for their efficacy in patients with kidney failure on hemodialysis is lacking. The underlying mechanisms remain incompletely understood, and whether cardiovascular benefits depend on residual kidney function is unknown.The Dapagliflozin in Hemodialysis (DAPA-HD) trial (NCT05179668) is an academic, multicenter, randomized, double-blind, placebo-controlled trial designed to assess the cardiovascular effects of dapagliflozin in 220 patients with kidney failure receiving hemodialysis. Stratified block randomization was based on patient-reported residual urine volume. The primary endpoint is the change in left ventricular mass indexed to body surface area using echocardiography after six months of treatment. A prespecified subgroup analysis will compare treatment effects between patients with residual urine output >200 mL/24 hours versus ≤200 mL/24 hours. Secondary endpoints include additional echocardiographic assessments, changes in biomarker concentrations, quality of life, and clinical events.RESEARCH DESIGN AND METHODSThe Dapagliflozin in Hemodialysis (DAPA-HD) trial (NCT05179668) is an academic, multicenter, randomized, double-blind, placebo-controlled trial designed to assess the cardiovascular effects of dapagliflozin in 220 patients with kidney failure receiving hemodialysis. Stratified block randomization was based on patient-reported residual urine volume. The primary endpoint is the change in left ventricular mass indexed to body surface area using echocardiography after six months of treatment. A prespecified subgroup analysis will compare treatment effects between patients with residual urine output >200 mL/24 hours versus ≤200 mL/24 hours. Secondary endpoints include additional echocardiographic assessments, changes in biomarker concentrations, quality of life, and clinical events.The DAPA-HD trial is the first trial specifically evaluating the cardiovascular and hemodynamic effects of dapagliflozin in patients with kidney failure receiving maintenance hemodialysis with and without residual urine output.CONCLUSIONThe DAPA-HD trial is the first trial specifically evaluating the cardiovascular and hemodynamic effects of dapagliflozin in patients with kidney failure receiving maintenance hemodialysis with and without residual urine output.

Background Chronic fluid overload is associated with higher mortality in dialysis patients; however, the link with cardiovascular morbidity has not formally been established and may be influenced by subclinical inflammation. We hypothesized that a relationship exists between fluid overload and [i] cardiovascular laboratory parameter as well as between fluid overload and [ii] inflammatory laboratory parameters. In addition, we aimed to confirm whether volume status correlates with nutritional status. Methods We recorded baseline characteristics of 244 hemodialysis patients at three hemodialysis facilities in Vienna ( Austria ) and determined associations with volume measurements using the body composition monitor ( Fresenius/Germany ). In one facility comprising 126 patients, we further analyzed cardiovascular, inflammatory and nutritional parameters. Results We detected predialysis fluid overload (FO) in 39% of all patients (n = 95) with FO defined as ≥15% of extracellular water (ECW). In this subgroup, the absolute FO was 4.4 +/-1.5 L or 22.9 ± 4.8% of ECW. A sub-analysis of patients from one center showed that FO was negatively associated with body mass index (r = -0.371; p = <0.001), while serum albumin was significantly lower in fluid overloaded patients (p = 0.001). FO was positively associated with D-Dimer (r = 0.316; p = 0.001), troponin T (r = 0.325; p < 0.001), and N-terminal pro-B-type natriuretic peptide (r = 0.436; p < 0.001), but not with investigated inflammatory parameters. Conclusions Fluid overload in HD patients was found to be lower in patients with high body mass index, indicating that dry weight was inadequately prescribed and/or difficult to achieve in overweight patients. The association with parameters of cardiovascular compromise and/or damage suggests that fluid overload is a biomarker for cardiovascular risk. Future studies should determine if this applies to patients prior to end-stage renal disease.

SARS-CoV-2 led to considerable morbidity/mortality worldwide and tremendously impacted on daily life. Strict lockdown measures were implemented early to contain the viral outbreak in Austria. Massive changes in organizational structures of healthcare facilities followed with unclear implications on the care of non-COVID-19-affected patients. We studied the nationwide impact of COVID-19 on kidney transplantation in Austria during the first six months of 2020. Concurrent with general lockdown measures, all kidney transplant activity was suspended from 13 March to 9 April. Nevertheless, between January and June, total transplant (p = 0.48) and procured donor organ numbers (p = 0.6) did not differ significantly from earlier years. Ten (0.18%) of 5512 prevalent Austrian kidney transplant recipients were diagnosed with SARS-CoV-2. The case fatality rate (one death; 10%) in renal transplant patients was less than in other countries but higher than in Austria’s general population (2.4%). We conclude that early and strict general lockdown measures imposed by the government allowed an early, however cautious, re-opening of Austrian transplant programs and played a crucial role for the favorable outcomes of SARS-CoV-2 in Austrian kidney transplant patients. Even though it may be uncertain whether similar results may be obtainable in other countries, the findings may support early intervention strategies during similar episodes in the future.

The majority of approved CAR T cell products are based on the FMC63-scFv directed against CD19. Surprisingly, although antigen binding affinity is a major determinant for CAR function, the affinity of the benchmark FMC63-scFv has not been unambiguously determined. That is, a wide range of affinities have been reported in literature, differing by more than 100-fold. Using a range of techniques, we demonstrate that suboptimal experimental designs can cause artefacts that lead to over- or underestimation of the affinity. To minimize these artefacts, we performed SPR with strictly monomeric and correctly folded soluble CD19, yielding an FMC63-scFv affinity of 2–6 nM. Together, apart from analyzing the FMC63-scFv affinity under optimized conditions, we also provide potential explanations for the wide range of published affinities. We expect that this study will be highly valuable for interpretations of CAR affinity-function relationships, as well as for the design of future CAR T cell generations.

Within a pilot study, after pedological and mineralogical characterization, various kinetic models were tested to fit lead (Pb)-mobilization kinetics from soils at historic mining and smelting sites. Pb mobilization was obtained by modified electro-ultrafiltration (EUF) after addition of diethylenetriaminepentaacetic acid (DTPA) at variable conditions of extraction. 10 fractions were sequentially produced, under mild conditions at 20°C/200 V (to simulate an initial release) for fractions 1–5, and subsequently harder conditions at 80°C/400 V (to simulate a long-term release) for fractions 6–10. The special samples treated within this work yielded higher extraction rates within the first runs. Closest fits in terms of the coefficient of determination (R2) were obtained from the 2nd order polynomial model y = a + bt + ct2, and in terms of re-calculated results by the parabolic equation y = a + b √t. The fitted constants obtained by the modified EUF method correlated better with soil pH than with organic carbon and clay contents. From this, it remains open, whether the dissolution of the Pb-minerals in the electric field or concentration resp. diffusion of the DTPA is rate-determining.