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Every hemodialysis session starts with the question of how much fluid should be removed, which can currently not be answered precisely. Herein, we first revisit the "probing-dry-weight" concept, using the historical example of Tassin/France (practicing also "long, slow dialysis"): Mortality outcomes were, in the 1980s, better than registry data, but are nowadays similar to European average. In view of the negative primary end point in a recent trial on dry weight assessment, based on lung ultrasound-guided evaluation of fluid excess in the lungs, and a meta-analysis of prospective studies failing to show that bioimpedance-based interventions for correction of volume overload had a direct effect on all-cause mortality, we ask how to ever move forward. Clinical reasoning demands that as much information as possible should be gathered on the fluid status of patients undergoing dialysis. Besides body weight and blood pressure, measurements of bioimpedance and dialysate bolus-derived absolute blood volume can in principle be automatized, whereas lung ultrasound can be obtained routinely. In the era of machine learning, fluid management could consist of flexible target weight prescriptions, adjusted on a daily basis and accounting even for fluctuations in fluid-free body mass. In view of all the negative prospective results surrounding fluid management in hemodialysis, we propose this as a "never-give-up" approach.

Rationale: Current estimation of body fluid volumes in hemodialysis patients using bioimpedance analysis assumes constant specific electrical characteristics of biological tissues despite a large variation in plasma Na+ concentrations [Na+], ranging from 130 to 150 mmol/L. Here, we examined the potential effect of variable [Na+] on bioimpedance-derived volume overload. Method: Volumes were calculated from published whole-body extra- and intracellular resistance data and relationships using either “standard” or “revised” specific electrical characteristics modeled as functions of [Na+]. Result: With “standard” assumptions, volumes increased with increasing [Na+]. The increase in volume overload was about 0.5 dm3 and 3% of extracellular volume per 10 mmol/dm3 of [Na+] in a 75 kg patient. This increase was abolished when the same bioimpedance data were analyzed under “revised” conditions. Discussion: The overestimation in extracellular volume overload in the range of 0.5 dm3 per 10 mmol/dm3 [Na+] perfectly matches the positive relationship determined in a large cohort of hemodialysis patients. The bias may be considered moderate when interpreting data of individual patients, but may become important when comparing data of larger patient groups. The bias disappears when analysis of bioimpedance data accounts for differences in tissue electrical properties, using individual [Na+].

Background The secretion, distribution, and elimination of insulin in response to a bolus of glucose injected during regular hemodialysis was modeled to quantify the intra-dialytic mass balance of glucose and insulin in patients without (D0) and with type 2 diabetes (D1). Methods A two-compartment regional blood flow model with shared compartments and dynamics for glucose, insulin and c-peptide was used to identify parameters of insulin and c-peptide co-secretion, first- and second-pass hepatic insulin extraction, as well as insulin-independent and insulin-dependent glucose utilization. Experimental data from a previous study obtained in 21 D0 and 14 D1 were used to identify kinetic model parameters and the fractions of glucose and insulin removed by dialysis. Results Modeled gains for insulin secretion (β1 = 0.015 vs. 0.084 L/min, β2 = 0.004 vs. 0.666 L) were lower in D1, resulting in a lower total insulin secretion (Mi = 6.40 vs. 38.0 nmol). Hepatic insulin extraction was high (Eihep = 0.558 vs. 0.638) and only slightly smaller in D1. The fraction of insulin removed by dialysis (Fid = 0.07 vs. 0.05) was small and comparable between D1 and D0. Modeled gains for insulin-dependent glucose uptake (γ = 0.38 vs. 1.34 L2/nmol/min) were lower whereas those for insulin-independent glucose uptake (λ = 0.14 vs. 0.067 L/min) were higher in D1. The fraction of glucose removed by dialysis (Fgd = 0.31 vs. 0.28) was higher in D1. Conclusion Apart from expected differences in modeled secretion and glucose utilization in patients with and without diabetes an intravenous bolus of glucose causes only small differences in overall glucose and insulin balance during a typical hemodialysis treatment.

BACKGROUND AND AIMS Blood volume (BV) is tightly controlled by the kidneys and the interstitial space plays an important role in this control. The interstitial space serves as a volume buffer in case of volume excess or volume depletion. It is the purpose of this buffer to maintain adequate circulatory and diastolic filling pressures, and thereby to maintain a functional circulation of the blood. BV is approximately one-third of the extracellular volume (ECV) under physiologic conditions. In haemodialysis patients without renal function, ECV is expanded because fluid is accumulated in the interdialytic period. This volume excess has to be removed during dialysis by ultrafiltration (UF) of blood. The question therefore arises, i) how is this volume excess distributed between intra-and extravascular compartments in dialysis patients and ii) how is this distribution affected by UF? METHOD Blood and extracellular volumes were measured in 79 stable chronic haemodialysis patients with moderate volume overload (1.85 ± 1.22 L). Immediately before treatment, ECV and volume overload were evaluated by bioimpedance spectroscopy using the body composition monitor [BCM, Fresenius Medical Care (FMC), Bad Homburg, Germany]. ECV at the end of treatment was calculated by subtracting the intra-dialytic weight loss from pre-dialysis ECV. The actual BV at the beginning of dialysis was determined by indicator dilution, using an online infusate bolus of 240 mL which was administered immediately after the beginning of the dialysis session and subsequent calculation using the data of the relative BV monitor integrated into the haemodiafiltration machine 5008 [Fresenius Medical Care (FMC), Bad Homburg, Germany]. BV at the end of the dialysis session was calculated from the measurement of BV at the beginning and the relative BV at the end of dialysis. RESULTS The relationship of BV (5.76 ± 1.54 L) to ECV (17.91 ± 3.90 L) was 0.321 ± 0.039 at dialysis start and 0.319 ± 0.040 at the end (BV 5.20 ± 1.41 L, ECV 16.22 ± 3.57 L). The mean deviation between pre- and post-dialysis was −0.002 ± 0.018. There were strong correlations (P CONCLUSION These data show that i) the blood to extracellular volume ratio in haemodialysis patients is close to one-third assumed under physiologic conditions and that ii) this ratio remains unchanged in spite of UF. The constant relationship between the two compartments is maintained under conditions of haemodialysis with the rapid volume removal by UF. This confirms previous findings that the vascular refilling volume is only about 70% of UF volume during dialysis. Despite the lack of kidney function, the mechanisms to adequately distribute volume excess between intra- and extravascular appear to be maintained. The volume shift between plasma and interstitial volume prevents both an inter-dialytic cardio-vascular burden and intra-dialytic hypotension. Therefore, haemodialysis patients with moderate volume overload are likely to be adequately protected from volume-related complications. To the best of our knowledge, this is the first time that these relationships are reported in dialysis patients.

Long dialysis treatments are generally assumed to mitigate the ultrafiltration (UF) induced volume perturbation and to improve vascular refilling because of reduced UF rates and sufficient time for volume re-equilibration. The time course of vascular refilling was therefore examined during extended nocturnal dialysis.For each hour of dialysis, vascular refilling volume was calculated from the absolute blood volume changes and UF volume removed. Absolute blood volume was estimated by indicator dilution at the beginning of dialysis and then tracked with a relative blood volume monitor. The refilling fraction was defined as the ratio of refilling volume to UF volume.Ten stable chronic hemodialysis (HD) patients were studied during extended (7 h) nocturnal treatment sessions. Specific UF rate was 4.8 ± 1.8 ml/kg/h. In the 1 h, refilling volume amounted to only 23% of UF volume. Thereafter, refilling fraction steeply increased and reached maximum values in the 2, 3 and 4 h at about mean 90% (91.5%, 88.7%, and 91.1% respectively). From the 5 h on, refilling volume decreased (5 h 81.3%, 6 h 72.5%, 7 h 70.0% of UF volume). Cumulative refilling reached 73.6% of UF volume after 4 h of treatment time. This did not change during the further course of HD. Cumulative refilling volume showed a strong correlation (r = 0.94; p 0.001) with UF volume. The ratio of blood volume to extracellular volume (RIn spite of low-UF rates and extended treatment times, overall refilling fraction reached only 74% and was not different from the refilling fraction observed in regular HD. This value seems to represent a point where UF-induced volume perturbation is adequately compensated by physiologic control mechanisms.

Background & Aims Solute generation rates, distribution volumes and compartment effects control the in vivo efficiency of any extracorporeal therapy such as extracorporeal liver support (ELS) used to remove bile acids accumulating in acute-on-chronic liver patients. The aim of this study was to identify and to examine kinetic parameters of two major bile acids using mathematical modeling. Methods The kinetics of cholic (CA) and chenodeoxycholic acid (CDCA) were described by one- and two-compartment models with central elimination by decreasing or constant extracorporeal clearance, constant bile acid generation rate, and constant apparent distribution volume. Concentration profiles collected in 13 ELS sessions done in 8 patients were included for model calculations Results For the one-compartment model, the average volumes and generation rates were 30 ± 6 [l], 0.19 ± 0.06 [μmol/min] for CA and 22 ± 5 [l], 0.29 ± 0.08 [μmol/min] for CDCA, respectively. For the one-compartment model and average normalized concentrations, the volumes and generation rates were 25 [l], 0.28 [μmol/min] for CA and 18 [l], 0.37 [μmol/min] for CDCA, respectively. For the two-compartment model, average normalized concentrations, the same initial concentration in both compartments, and assuming a 10% post-treatment rebound, the volume and generation rates were 25 [l], 0.27 [μmol/min] for CA and 19 [l], 0.32 [μmol/min] for CDCA, respectively. Conclusions The generation rate for CDCA is higher when compared to that of CA and independent of the number of compartments. Assuming a constant extracorporeal clearance overestimates generation rate and distribution volume. The kinetic parameters of one- and two-compartment models are comparable for the same bile acid.

Background: Increased intra-abdominal pressure (PIA) leads to venous congestion in splanchnic and adjoining circulations. The aim is to examine whether PIA in peritoneal dialysis (PD) affects the mobilization of extracellular fluid from the lower body in supine body position. Methods: Patients were studied during a regular peritoneal equilibration test (PET) in supine body position using multifrequency bioimpedance analysis to determine extracellular resistance and absolute volume overload (AVO) in wrist-to-ankle (W2A) as well as in ankle-to-ankle (A2A) configurations. Measurements were taken at baseline (T0) after draining the peritoneal cavity, at T1 shortly after filling with 2 L of standard dialysate, and at T2 before taking the 2 h PET samples. PIA was measured from the column height in the PD catheter. Extracellular resistance in the lower extremities (RL) was taken as half of the A2A resistance. Results: Eighteen patients (56 ± 15 years, 76 ± 21 kg, body mass index (BMI) 26.4 ± 7 kg/m2, 13 men) were studied. After having assumed a supine body position for the duration of 17, 77, and 155 min, AVO continuously decreased from 1.6 ± 1.3 (T0) to 1.2 ± 1.5 (T1) and 1.0 ± 1.4 L (T2). RL significantly increased from 238 ± 57 (T0) to 254 ± 62 (T1) and 264 ± 67 Ohm (T2). This increase was negatively correlated to BMI and PIA measured at any time point, but not to net ultrafiltration volume. Conclusions: Orthostatic fluid shifts from the lower limbs may take up to 2 h in supine PD patients, especially with high BMI and PIA because of venous congestion in splanchnic and adjoining circulations.

Dialyzer manufacturers characterize performance of their devices based on measurements of clearance using crystalloid solutions. Typically, in vitro dialyzer mass transfer area coefficients for urea (K0A) are substantially higher than values measured in vivo. The reason for this reduction has not been clearly determined. We hypothesized that the known effect of viscosity on reducing solute diffusivity might partially or fully account for this reduction. In vitro dialyzer clearances of urea, glucose, and lactate were measured using crystalloid solutions as well as bovine blood with varying hematocrit and plasma viscosity under a wide range of operating conditions. Viscosities of crystalloid solutions, of blood plasma, and of whole blood were measured at 37°C at a shear rate of 100/s. Diffusivity and relative K0A values (K0Arel) in eight dialyzers were computed for each solute under these different conditions. Plasma was 1.84 times more viscous compared with crystalloid solution (ηrel = 1.84), suggesting a correction multiplier of 1/ηrel = 0.54 for in vivo K0A relative to the in vitro value. Experimental K0Arel at that ηrel was on average reduced to 52% of crystalloid in vitro K0A values. The multiplier 0.52 measured in this study is close to the multiplier 0.55 predicted for average plasma viscosities and also close to the multiplier 0.54 assumed for urea kinetic modeling to provide reasonable urea distribution volumes. The known effect of viscosity on solute diffusivity is therefore sufficient to explain the reduction in dialyzer K0A for urea and glucose in vivo compared with in vitro measurements.

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Background and Aims Few studies have focused on the imbalance of the autonomic nervous system during hemodialysis (HD), although it seems to be an important factor for the maintenance of blood pressure. The aim of this work was to assess the impact of hemodialysis (HD) and glucose injection upon entropy of heart rate and blood pressure during HD session in end stage renal disease (ESRD) patients with and without diabetes mellitus (DM) type 2. Method 21 patients without DM (NDO), in age 54,95 +/-13,08 y.o., and 10 DM patients, in age 69,70 +/- 8,27 y.o., were studied during HD. 30 minutes after dialysis begins, 40% glucose solution was administered in the amount of 0.5g/kg body dry-weight (constant rate of 1 mL/s). The cardiovascular signals were extracted from the recordings using Portapres® system. The analysis was performed using Amplitude Aware Permutation Entropy (AAPE). The parameters of AAPE were set as d=7, A=0.5. All statistical analysis were performed on significance level α=0.05. The comparisons between groups were conducted with Mann-Whitney test with Holm corrections. The comparisons in time points were performed using Friedman test with post-hoc (Wilcoxon test with Holm corrections). The calculations of AAPE and all statistical analysis were performed with Matlab R2020a and R. Results The results are presented in table. It was found that AAPE(HR) tends to decrease during dialysis (NS) and increases only in the DM group after glucose injection (p=0.019); without difference between groups. There were no differences in AAPE of blood pressure between the groups, but hemodialysis reduces AAPE(fiSYS) in both groups (p Conclusion AAPE(HR)tends to decrease during HD, and glucose injections increase AAPE(HR) in DM patients. Hemodialysis reduce, and glucose injections increase AAPE of blood pressure especially in NDO. A weaker response to hemodialysis and glucose injection in diabetic patients may be caused by impairment of the autonomic system, and may have clinical impact – may leads to faint. Glucose administration does not prevent autonomic system disorders in patients with DM.

Online hemodiafiltration machines equipped with a blood volume monitor and the possibility to rapidly infuse exact amounts of ultrapure dialysate into the extracorporeal circulation can be used to determine absolute blood volume in clinical practice. The aim of the present study was to evaluate the reproducibility of such measurements. Intra-individual reproducibility was evaluated in four measurements taken in hourly intervals within the same dialysis treatment. Ten patients were studied. Absolute blood volumes measured at the beginning and after 1 hour of dialysis were significantly different (80.6 ± 14.5 and 63.9 ± 14.3 mL/kg, P < .001) and highly reproducible between the last three measurements (63.9 ± 14.3, 61.4 ± 13.8, and 60.9 ± 13.9 mL/kg, P = n.s.). Measurement of absolute blood volume after 1 hour of treatment is more precise than earlier measurements and might be better suited for guidance of ultrafiltration.

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.

Twin-to-twin transfusion syndrome (TTTS) in monochorionic-diamniotic twin pregnancies usually requires fetoscopic laser ablation (FLA) followed by amniodrainage (AD). Perioperative maternal hemodynamic changes and hemodilution have been observed. Little is known about the underlying pathophysiology. We aimed to evaluate the impact of high volume amniodrainage on intrauterine pressure, placental thickness and maternal blood characteristics. A total of 18 cases of TTTS were included in this prospective pilot study. All patients were treated with FLA and subsequent AD. Intrauterine pressure and placental thickness were assessed before, during and after amniodrainage. Maternal hemoglobin, hematocrit and serum albumin were measured at admission and 24 h after the intervention. Amniodrainage led to a decrease in mean intrauterine pressure (from 30.1 &plusmn, 8.1 mmHg to 17.6 &plusmn, 3.6 mmHg (p &lt, 0.001)) and an increase in mean placental thickness (from 16.8 &plusmn, 6.4 mm to 31.83 &plusmn, 8.64 mm (p &lt, 0.001)). There was a positive correlation between changes in placental thickness and the amount of amniodrainage during intervention (Pearson&rsquo, s Rho 0.73, p = 0.001). Hematocrit decreased from 33.4 &plusmn, 3.8 (%) to 28.4 &plusmn, 3.5 (%), i.e., an increase in relative blood volume by 18 &plusmn, 10.2% (p &lt, 0.001). Albumin decreased from 37.9 &plusmn, 0.9 g/L to 30.7 &plusmn, 2.2 g/L, i.e., an increase in relative plasma volume by 24 &plusmn, 8.1% (p &lt, 0.001). Amniodrainage leads to uterine decompression, increased placental thickness and subsequent maternal hemodilution. We propose the term &ldquo, amniodrainage-induced circulatory dysfunction&rdquo, for these specific maternal hemodynamic changes in the treatment of twin-to-twin transfusion syndrome.

Background and Aims Current on-line haemodiafiltration (HDF) machines equipped with a blood volume monitor (BVM) and an on-line bolus function have the potential for measuring absolute blood volume (aBV). Recently, we developed a simple method to determine absolute BV in everyday dialysis sessions. The aim of the present study was to evaluate the reproducibility of measurements. Method Intra-individual reproducibility was studied in 10 patients during a single dialysis session by 4 measurements of absolute BV: immediately after beginning before ultrafiltration (UF) was started, and after one, two and three hours. ABV was determined by indicator dilution. A defined volume bolus of 240 mL dialysate was infused into the venous blood line by pressing the emergency button of the HDF machine 5008 (FMC). For this reason, total UF volume was increased by 1L. UF was automatically stopped during and after the infusion. The resulting increase in relative blood volume (RBVpost-RBVpre) was measured by the ultrasonic relative BVM incorporated in the dialysis machine. ABV was measured in hourly intervals and for assessment of reproducibility the volume at treatment start (t=0) where RBV is 100% was calculated for all measurements as: aBV in mL = bolus volume 240 mL x 100% / increase RBV in % ABV data were normalized for body mass at dry weight (in mL/kg). Additionally, in 5 patients the RBV graph was monitored immediately at the beginning of dialysis without UF in a separate dialysis session. Results ABV at t=0 were consistently larger when calculated from measurements done immediately after the beginning compared to measurements obtained after 1 h (6.52 ± 1.40 L or 80.6 ± 14.5 mL/kg vs. 5.16 ± 1.40 L or 63.9 ± 14.3 mL/kg). Specific BV derived from 2 and 3 h measurements did not significantly differ from the measured volumes after 1 hour (61.4 ± 13.8 mL/kg, and 60.9 ± 13.9 mL/kg). The standard deviations of the 3 examinations in the same study patient during a further course of dialysis were between 0.6 and 5.3 ml/kg (ø 2.6 ml/kg). In a separate session, RBV decreases without UF at the beginning of dialysis in the first 3 minutes by 0.5 % and in 5 minutes by 0.6 %. Conclusion If BV is diluted by additional priming volume and bolus volume, a part of this volume will leave the circulation. This represented the time frame where the bolus was initially infused and the measurements were carried out. This loss is caused by the reduction in plasma colloid osmotic pressure induced by the dilution thereby changing the microvascular filtration equilibrium. The increase in RBV display is not solely caused by the bolus volume in this time and, and therefore, calculated BV would be overestimated by about 17 mL/kg. If measurement is performed at a later time, UF will take place and, consequently, refilling. This inward drive matches the outward bolus escape as a counterforce. BV measurement during a further course of dialysis is well reproducible with a deviation of only ± 2.6 ml/kg. The method would therefore be sufficiently precise in clinical practice. Therefore, we propose the determination of aBV only after 1 hour dialysis when a sufficient refilling takes place. With a software modification, the BV measurement could be routinely automated during each dialysis treatment. Manufacturers are asked to implement this technology in their devices.

Background and Aims Refilling volume had not been a measurable parameter in clinical practice so far, because the knowledge of absolute blood volume (BV) is necessary. Recently, we developed a simple method to determine absolute BV, thus enabling quantification of the refilling volume. The overnight dialysis is particularly suitable for studying the refilling process due to negligible external influences and the extended treatment time. Method At the beginning of the dialysis (t=0), before starting the ultrafiltration (UF), a defined online bolus of 240 ml dialysate was infused by pressing the emergency button on the haemodiafiltration (HDF) machine (5008, FMC). The subsequent increase in relative BV (RBVpost-RBVpre) was measured with the integrated BV monitor, and absolute BV at t=0 was calculated: absolute BV in ml = bolus volume 240 ml x 100% / increase in relative BV in%. Absolute BV at any other time t was calculated as: Vt = V0 x RBVt (in %) / 100 At constant UF rate refilling volume (Vref) is given for every hour (h) as: Vref h = UFV h – drop in absolute BVh (beginning – end) The refilling fraction is expressed as refilling/UF ratio: Ref% = Vref/UFV x 100, in % Before treatment, volume overload was evaluated by bioimpedance spectroscopy (BIS) using the body composition monitor (FMC). Results Refilling volume and refilling fraction were studied in 10 stable chronic haemodialysis (HD) patients during an extended (7 hour) nocturnal HD session. Specific BV at treatment start was 74.9 ± 11.8 mL/kg and dropped to 68.6 mL/kg at dialysis end. The constant UF rate was set to 406 ± 120 mL/h (specific UF rate 4.81 ± 1.83 mL/kg/h). In the first hour refilling volume amounted only to 23% of UF volume. Refilling fraction reached its maximum in the 2nd, 3 rd and 4th hour at about mean 90% (91.5%, 88.7%, and 91.1% respectively) of UF volume. From the 5th hour on, refilling volume and refilling fraction decreased (5th hour 81.3%, 6th hour 72.5%, and 7th hour 70.0% of UF volume). In the 5th hour, cumulative UF volume exceeded volume overload (1.1 ± 1.0 L) measured by BIS in 9 of 10 patients. Refilling fraction cumulatively increased up to the 4th hour. Thereafter, cumulative ratio remained constant at 70 – 75% due to the decrease in refilling volume. This did not change during the further course of dialysis. Cumulative refilling volume showed a strong correlation (r2 = 0.88; p Conclusion After the first hour, when sufficient refilling takes place, refilling volume is in a stable ratio of approximately 90 % of UF volume. Refilling is low in the first hour, and, therefore, refilling volume amounted cumulatively only about 70 to 75% of UF volume during usual dialysis duration. Thereby, absolute BV will be reduced by approximately 250 to 300 ml per liter UF. This must be taken into account in volume management in order to avoid intradialytic complications. As expected, refilling decreases when volume overload in the interstitial space is removed. Due to the reduced refilling, there will be an additional gap in BV.

AIMS The disposal of a glucose bolus was studied to identify glucose metabolism in patients with and without type 2 diabetes mellitus (T2DM) during their regular hemodialysis (HD) treatment. METHODS Plasma glucose, insulin, and c-peptide concentrations were measured during a 60 min observation phase following a rapid glucose infusion (0.5 g/kg dry weight). Glucose disposition and elimination rates were determined from kinetic analysis, and insulinogenic index was calculated. Insulin resistance (RHOMA) was determined by homeostatic model assessment (HOMA). RESULTS 35 HD patients (14 with T2DM) distinguished by a higher age (median: 70 vs. 55 y, p

COVID-19, a disease caused by a novel coronavirus, is a major global human threat that has turned into a pandemic. This novel coronavirus has specifically high morbidity in the elderly and in comorbid populations. Uraemic patients on dialysis combine an intrinsic fragility and a very frequent burden of comorbidities with a specific setting in which many patients are repeatedly treated in the same area (haemodialysis centres). Moreover, if infected, the intensity of dialysis requiring specialized resources and staff is further complicated by requirements for isolation, control and prevention, putting healthcare systems under exceptional additional strain. Therefore, all measures to slow if not to eradicate the pandemic and to control unmanageably high incidence rates must be taken very seriously. The aim of the present review of the European Dialysis (EUDIAL) Working Group of ERA-EDTA is to provide recommendations for the prevention, mitigation and containment in haemodialysis centres of the emerging COVID-19 pandemic. The management of patients on dialysis affected by COVID-19 must be carried out according to strict protocols to minimize the risk for other patients and personnel taking care of these patients. Measures of prevention, protection, screening, isolation and distribution have been shown to be efficient in similar settings. They are essential in the management of the pandemic and should be taken in the early stages of the disease., Graphical Abstract Graphical Abstract

The aim of this study was to examine the relationship between hydrostatic trans-membrane pressure (TMPh ) and colloid osmotic pressure (COP) in low-flux (LF) and high-flux (HF) dialyzers. Hydrostatic pressures were measured in dialyzers distinguished by their ultrafiltration coefficient Kuf (16 and 85 mL/h/mm Hg) under constant dialysate flow and variable blood flow (Qb ) ranging from 0 to 400 mL/min using (i) alginate (70 kDa) dissolved in dialysate, (ii) diluted, undiluted, and concentrated plasma, or (iii) whole blood at different hematocrit, all in absence of ultrafiltration (UF). For a given fluid, TMPh linearly increased with increasing Qb . The intercept of the linear TMPh to Qb relationship correlated with measured COP with an average bias of 1.00 ± 2.26 mm Hg and a concordance correlation coefficient of 0.98. The slope of the linear TMPh to Qb relationship increased with increasing sample viscosity and was much larger in HF dialyzers under otherwise identical operating conditions, most likely because of increased internal filtration. The TMPh to Qb relationship measured in dialyzers in absence of UF can be described by the intercept related to measured COP and the slope related to internal filtration. This relationship could be of interest to estimate internal filtration and COP under in vivo conditions.

Introduction: Adequate volume management removing excess volume and at the same time avoiding intradialytic morbid events (IME) remains a core problem in current hemodialysis (HD) therapy. Recently, we developed a feasible method to determine absolute blood volume (Vs, in mL/kg) in patients on HD. The aim of this study was to investigate the suitability of Vs measurements for volume management. Methods: Following a 4 week baseline phase to quantify the frequency of IME, volume status was determined in a single specified HD session during which Vs was measured using dialysate dilution, volume overload (Vo, L) was measured using bioimpedance spectroscopy, and the occurrence of IME was recorded. Target weight was then adjusted and the frequency of IME was recorded during 4 weeks of follow-up. Findings: Forty-five patients participated in this study. Twenty-two (49%) patients experienced 66 IME in 12% of HD treatments during baseline. In 15 (33%) patients who experienced IME during volume assessment both Vs (60.7 ± 4.0 vs. 73.7 ± 11.3 mL/kg, P

Purpose Identifying the primary etiology of cardio-renal syndrome in a timely manner remains an ongoing challenge in nephrology. We hypothesized that hypertensive kidney damage can be distinguished from chronic glomerulonephritis at an early stage of chronic kidney disease (CKD) using ultrasound (US) Doppler sonography. Methods Fifty-six males (age 54 ± 15, BMI 28.3 ± 3.5 kg/m2) with hypertension and stable CKD at stages 2–4 [38 with essential hypertension (HT-CKD); 18 with glomerulonephritis (GN-CKD)] were studied. Blood tests, UACR, echocardiography, ABPM, carotid IMT, and an ultrasound dynamic tissue perfusion measurement (DTPM) of the renal cortex were performed. Results HT-CKD patients had reduced proximal renal cortex perfusion as well as reduced total and proximal renal cortex arterial area. Proximal renal cortex arterial area ≤0.149 cm2 identified hypertension-related CKD with a sensitivity of 71% and a specificity of 78% (AUC 0.753, p

The association between higher ultrafiltration rates and poor outcomes in hemodialysis patients has received increased attention, to the point that various regulatory entities are considering adding ultrafiltration rate as a quality measure to be monitored and controlled. Most of the discussion to date has focused on ultrafiltration rate scaled to body weight, or more correctly, body mass (ml/hour per kg). One outcome study suggests that ultrafiltration rate might best be not scaled at all to body size, as modestly higher ultrafiltration rate in very small-size patients may be associated with some survival benefit, probably via increased dietary intake. Outcomes studies also suggest that the risk of exceeding a weight-scaled ultrafiltration target may be magnified in very large patients, and that body weight-scaled ultrafiltration targets in such patients should be set a lower level. Here, we present an analysis, based on physiological hemodynamic arguments, that it would be better to scale ultrafiltration rate to body surface area rather than to body mass. Whatever ultrafiltration rate is scaled to, attempts to restrict ultrafiltration rate by limiting interdialytic weight gain in small, possibly malnourished patients, should be done cautiously, to prevent an inadvertent lowering of intake of calories and dietary protein.

Background: It is commonly believed that insufficient vascular refilling leads to hypovolemia during hemodialysis and contributes to intradialytic morbid events (IME). But data of refilling volumes at the time of IME are lacking. Methods: We compared the vascular refilling in 10 patients with IME with 14 stable patients with normal blood volume at the dialysis end (66-80 mL/kg). Results: The refilling characteristics in patients with IME did not differ from those in stable patients. The refilling fraction (refilling/ultrafiltration [UF] ratio) was 73.8 ± 9.4% in patients with IME, and 70.2 ± 6.4% in patients with normal blood volume at the end of the treatment. Refilling volume strongly correlated with UF volume in both patient groups (r2 = 0.93 and r2 = 0.81, respectively). Conclusion: IME are associated with a specific blood volume below 65 mL/kg. Vascular refilling is a constant fraction of UF in stable as well as in symptomatic dialysis sessions.

Introduction The success of automatic feedback control systems to improve hemodynamic stability by preventing relative blood volume from dropping beyond a critical value during dialysis is limited. The aim of this study was to use one of these systems for control of absolute rather than relative blood volume to prevent volume-dependent morbid events. Methods Dialysis was delivered by a machine providing feedback control of ultrafiltration rates, relative blood volume monitoring, and accurate bolus infusion of 240 mL of dialysate to measure absolute blood volume at the beginning of dialysis. Critical relative blood volume required by the control algorithm was calculated from absolute blood volume at the beginning and a critical absolute blood volume of 67 mL/kg. Findings In 40 stable patients, ultrafiltration was guided by blood volume using the feedback algorithm of the integrated program. Blood volume was maintained in a narrow range above the prespecified minimal value of 67 mL/kg. At the end of dialysis, absolute blood volume ranged from 67.5 to 72.5 mL/kg (69.4 ± 1.3 mL/kg). No volume-dependent intradialytic morbid event occurred. Discussion A feedback control system for relative blood volume-controlled ultrafiltration can be used for control of absolute blood volume. A prescribed target of absolute blood volume can be converted into relative blood volume, and this can subsequently be reached automatically with the integrated feedback system of the dialysis machine. Intradialytic morbid events could be considerably reduced. The whole procedure could be completely automated without altering the hardware of the dialysis device.