Background: We developed a simple method to determine the absolute blood volume (V) during hemodialysis in everyday clinical practice and examined its relationship with volume overload, clinical relevance, and accuracy. Methods: The increase in relative blood volume (RBV_post - RBV_pre) measured before and after infusion of 240 ml of ultra-pure dialysate using the bolus function of a commercial online hemodiafiltration machine incorporating a relative blood volume monitor was applied to determine absolute blood volume. The specific blood volume (V_s, blood volume per kg body mass at dry weight, in ml/kg) was compared to volume status as assessed by bioimpedance analysis and clinical criteria. Results: The blood volume measured in 30 stable hemodialysis patients was 6.51 ± 1.70 l at the beginning, corresponding to a specific blood volume of 80.1 ± 12.8 ml/kg, and dropped to 5.84 ± 1.61 l or 72.0 ± 12.1 ml/kg at the end of the dialysis session, respectively. Specific blood volume correlated with volume status assessed both clinically and by bioimpedance analysis. Intradialytic morbid events occurred only in treatments where specific blood volume fell below 65 ml/kg. The reproducibility of the technique was better than 4% and the in vitro accuracy corresponds to a resolution in V_s of better than 1 ml/kg. Conclusion: Absolute blood volume can be easily measured at the beginning of the dialysis session using the current dialysis technology. Information about V and V_s could be a promising tool to avoid intradialytic morbid events. This technique could be completely automated without altering the hardware of currently available online dialysis devices. Therefore, it is recommended that this technique be integrated into all hemodiafiltration machines.

OBJECTIVES: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19–associated vasoplegic shock. DESIGN: Prospective, randomized controlled pilot study. SETTING: Eight ICUs at three sites of the tertiary-care university hospital Charité—Universitätsmedizin Berlin. PATIENTS: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 µg/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis. INTERVENTIONS: Randomization of 1:1 to receive CytoSorb for 3–7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4–5 d) and 4 days (IQR, 3–5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54–2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61–2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups. CONCLUSIONS: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.

Glomerular and tubulointerstitial soluble guanylate cyclase activity are discordantly altered in anti-thy1-induced chronic glomerulosclerosis. Stimulation of soluble guanylate cyclase signaling by Bay 41-2272 limits the progressive course of this model toward tubulointerstitial fibrosis and impaired renal function at least in part in a blood pressure-independent manner. The results suggest that soluble guanylate cyclase activation counteracts fibrosis and progression in chronic renal disease.

The reduction of blood volume below a critical threshold is assumed to trigger intradialytic morbid events (IME). Recently, we presented a simple method to determine the absolute blood volume during routine hemodialysis (HD) carried out without blood sampling and without injection of dyes or radiolabeled markers. Such information could be used to detect excessive volume reduction during HD and to prevent IME. Therefore, we performed a pilot study in IME-prone patients to identify the absolute blood volume at which they developed clinical symptoms. A volume of 240 mL of ultrapure dialysate was automatically infused into the extracorporeal circulation using the bolus function of a commercial online hemodiafiltration machine incorporating a blood volume monitor (BVM). The increase in relative blood volume (RBV) caused by the infusion was measured and used to determine the absolute blood volume at that time. The blood volume per kilogram body mass at the time of symptomatic IME was also determined. All IME-prone patients of a single-dialysis center were included in the study. Ten out of 12 patients became symptomatic at a specific blood volume between 65 and 56 mL/kg (mean 62 mL/kg) whereas RBV showed a wide scatter (82-97%). A specific blood volume of 65 mL/kg seems to represent the threshold for IME by this method. The technique could be completely automated without altering the hardware of the dialysis device. Present feedback systems for automated blood volume-controlled ultrafiltration could be adapted to maintain absolute blood volume above this critical volume to safely prevent volume-dependent IME.

Adjustment of target weight based on information of Vs, Vo, and IME appears as a feasible approach to reduce the frequency of IME.

Glomerular nitric oxide signaling via cGMP is markedly impaired during injury of anti-thy1 glomerulonephritis, while it is highly up-regulated during subsequent repair. Further pharmacologic soluble guanylate cyclase stimulation limits glomerular TGF-beta overexpression and matrix expansion, suggesting that the soluble guanylate cyclase enzyme represents an important antifibrotic pathway in glomerular disease.

Introduction Blood volume changes and vascular refilling during hemodialysis (HD) and ultrafiltration (UF) have been assumed to depend on volume overload (Vo ). It was the aim to study the magnitude of vascular refilling in stable HD patients with moderate volume expansion in everyday dialysis using novel technical approaches. Methods Patients were studied during routine dialysis and UF based on clinical dry weight assessment. Pre-dialysis Vo was independently measured by bioimpedance spectroscopy. Vascular refilling volume (Vref ) was calculated as: Vref  = Vuf  - ΔV, where ΔV is the absolute blood volume change determined by on-line dialysate dilution using a commercial on-line hemodiafiltration machine incorporating a relative blood volume monitor, and where Vuf is the prescribed UF volume. Findings Thirty patients (dry weight: 81.0 ± 17.8 kg) were studied. Pre-dialysis Vo was 2.46 ± 1.45 L. Vuf was 2.27 ± 0.71 L, specific UF rate was 6.45 ± 2.43 mL/kg/h, and since ΔV was 0.66 ± 0.31 L, Vref was determined as 1.61 ± 0.58 L, corresponding to a constant refilling fraction (Fref ) of 70.6 ± 10.6%. Vref strongly correlated with Vuf (r(2)  = 0.82) but was independent of Vo and other volumes. Fref was also independent of Vo and other volumes normalized for various measures of body size. Discussion While vascular refilling and Fref is independent of Vo in treatments with moderate UF requirements, intravascular volume depletion increases with increasing UF requirements. The relationship between blood volume and Vo needs to be more closely examined in further studies to optimize volume control in everyday dialysis.

Extended daily on-line HDF using maximum convective volume seems to improve the outcome of septic MOF, especially in the early phase. The investigated mode of treatment proved to be feasible, well tolerated and highly cost effective compared to conventional CRRT. At present, this procedure would be applicable at every ICU facility with nephrological support.