Dialysate Flow Research Articles

Automation and innovation in home hemodialysis machines.

In this review, we discuss the timeline of innovation and technologic development in home hemodialysis (HHD) in the United States and the legislative approvals that accompanied them. The most recently FDA-approved home hemodialysis devices provide features that include on-demand and batch dialysate generation, access disconnect for venous needle dislodgement, touchscreen interface with visual and auditory prompts and animations, drop-in sterilized cartridges with prestrung tubing, hot water disinfection of tubing allowing extended-use, dialysate flow rates as high as 500 ml/min, as well as remote treatment monitoring capabilities. Furthermore, wearable/portable dialysis devices are currently under development to simplify dialysis delivery to patients with end-stage kidney disease. Home hemodialysis devices providing longitudinal hemodialysis across different clinical settings, virtual reality headsets for more personalized training, automated patient support, as well as wearable device development and innovations give hope for a future where home hemodialysis is more accessible and seamless.

Computational Fluid Dynamics (CFD) in Arteriovenous (AV) Graft Implantation Through End-to-Side Anastomosis with Varying Tube Diameters Across Different Vascular Access Locations for Dialysis Treatment.

Background/Objectives: Arteriovenous (AV) graft is a procedure for hemodialysis performed in the arm. Optimizing AV graft design is vital to enhance haemodialytic efficiency in patients with kidney disease. Despite being a standard procedure, making it work optimally is still difficult due to various graft diameters and anastomosis configurations, which have limited studies. This research aims to find the ideal AV graft tube diameter on blood flow and pressure gradients and the ideal body site for AV graft implantation and to study their angles for dialysate flow. Methods: Nine models were designed in Autodesk Fusion 360 with 40°, 50°, and 60° angles each having 2 mm, 5.1 mm, and 14.5 mm diameters, all following specific equations on continuity, momentum (Navier-Stokes Equation)), and the Reynolds Stress Model (RSM). The CFD simulation of these models was performed in ANSYS Fluent with an established parameter of 0.3 m/s inlet velocity and stiff/no-slip graft and artery wall boundary condition. Results: As a result, the design with a diameter of 14.5 mm and a 40° angle was overall the most ideal in terms of minimal wall shear stress and turbulence. Conclusions: Thus the brachiocephalic area or the forearm is calculated to be the most optimal implantation site. Additionally, varying angles do affect dialysate flow, as smaller values cause less stress.

Relationship between septic acute kidney injury and adiponectin: A retrospective study in patients undergoing continuous plasma exchange with dialysis.

Adiponectin (APN) is a multimeric protein with anti-inflammatory properties that is specifically secreted by adipocytes. Continuous plasma exchange with dialysis (cPED) is a blood purification therapy in which plasma exchange is performed using a selective membrane plasma separator while the dialysate flows outside the hollow fibers. Patients with sepsis were divided into two groups based on the presence or absence of acute kidney injury (AKI) complications: AKI and non-AKI group. Plasma APN levels significantly increased after cPED in both groups. The creatinine levels in the AKI group before cPED were significantly higher than those in the non- AKI group. The plasma APN levels in the AKI group before cPED were significantly higher than those in the non-AKI group. cPED increased APN levels in both patients with and without AKI. Therefore, cPED therapy may be a promising intervention for increasing APN levels in patients with sepsis.

On the Temporal Evolution of Key Hemofilter Parameters-In Vitro Study under Co-Current Flow.

Effective permeability KP, the ultrafiltration coefficient (KUF), the sieving coefficient (SC), and the loss/permeation of proteins (primarily albumin) are key parameters/specifications characterizing hemofilter (HF) performance. However, there are uncertainties regarding their determination. This work aims (a) to demonstrate that the co-current flow (of blood and dialysate) can lead to beneficial unidirectional filtration (from blood/plasma to dialysate) under a fairly uniform local trans-membrane pressure (TMP), unlike the presently employed counter-current flow; (b) to study the temporal evolution of key HF performance parameters under co-current flow, particularly during the important early stage of hemocatharsis (HC). Experiments with human plasma and BSA solutions in co-current flow mode (for which a fluid mechanical model is developed) show a fairly uniform local/axial TMP, which also improves the local/axial uniformity of protein membrane fouling, particularly under (currently favored) high convective flux operation. Due to incipient membrane fouling, a significant temporal variability/decline in the effective KP is observed, and, in turn, of other parameters (i.e., the Kuf, SC, and permeation/mass flux Mm for albumin and total proteins). A satisfactory correlation of the albumin/protein mass flux Mm with permeability KP is obtained, indicating strong inter-dependence. In conclusion, co-current flow, allowing for a fair local TMP axial uniformity, enables the acquisition of accurate/representative data on the evolution of HF parameters, facilitating their interpretation and correlation. The new results provide a basis for exploring the clinical application of the co-current flow.

How low can we go with the dialysate flow? A retrospective study on the safety and adequacy of a water-saving dialysis prescription.

Green nephrology encompasses all initiatives in kidney care that have a positive impact on climate and environment. To prepare the dialysate, at least 120L of water are needed for one 4-h session with a dialysate flow (Qd) set at 500mL/min. A lower dialysate flow rate is associated with a significant reduction in the amount of water used. The aim of this study was to check whether change of Qd from 500mL/min to 300mL/min has a significant impact on dialysis adequacy. The study was a retrospective analysis. Due to administrative issues, a satellite dialysis center reduced their dialysate flow to 300mL/min for a month. The center then increased Qd to 500mL/min again. We analyzed laboratory data from 3months before dialysate flow reduction, in the month with Qd reduced to 300mL/min, and from 3months thereafter with Qd set at 500mL/min. Twenty-four people were included in the final analysis. There were no significant changes in urea reduction ratio caused by lower rate of Qd [64.50 (61.75-71.00) vs 67.00 (63.00-72.25) vs 69.00 (63.75-72.25), analysis of variance F(2,46)=0.71, P=.50]. Similarly, hemodialysis adequacy expressed by Kt/V did not differ at any Qd [1.23 (1.12-1.41) vs 1.25 (1.18-1.40) vs 1.35 (1.19-1.48), ANOVA F(2,46)=2.51, P=.09]. There was a small but statistically significant increase in mean predialysis potassium with lower Qd [potassium=5.18 (95% confidence interval, 95% CI, 4.96-5.44) vs 5.46 (95% CI 5.23-5.69) vs 5.23 (95% CI 4.99-5.47) mmol/L at Qd=500, 300 and 500mL/min, respectively, P=.039]. Reduction in dialysate flow rate to 300mL/min seems safe and does not cause any short-term negative effects in this small study. Thus, we might be able to achieve a similar therapeutic effect while saving water consumption. Larger, long-term studies incorporating patient-reported outcome measures are needed to confirm the efficacy of this approach.

Numerical and experimental investigation of solute transports through different types of dialyzer membrane

The flow and mass transport through different membrane types from different hemodialyzers are investigated in a co-current direction to emphasize the effect of solute diffusion through the dialyzer membranes. The numerical model consists of the blood flowing in a hollow fiber surrounded by a dialysate flow, where the mass transport and fluid flow were simultaneously calculated. The high flux dialyzers considered in the present study are FINEFLUX FIX-210S eco, ELISIO-210HR, and PEPA FDY-21B, which differ mainly in characteristics of the membrane structure and surface. Urea and maltodextrin solutions are used as model solutes to consider the effect of molecular size difference. The numerically predicted outlet concentrations closely align with experimental values, where the variation between predicted and measured values remain below 10% across all dialyzer types for urea solutions, and specifically below 8% for maltodextrin solution. Among the various dialyzers tested, FINEFLUX membrane could provide the highest maltodextrin clearance (83.09 ml/min) and overall mass transfer area coefficient (KoA) (119.56 ml/min) potentially due to its fast-diffusion characteristic. In this co-current flow study, the results suggest that urea transport is primarily influenced by flow control with minimal impact from boundary layers, while maltodextrin transport is predominantly governed by diffusion control.

Extracorporeal treatment in poisoning

In rare cases, intoxicated patients may require an extracorporeal procedure for enhanced toxin elimination. The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup provides consensus- and evidence-based recommendations regarding the use of extracorporeal procedures in the management of critically ill, poisoned patients, with ongoing updates. Extracorporeal clearance is highest for low molecular weight substances with low volume of distribution, low plasma protein binding, and high water-solubility. To maximize the effect of extracorporeal clearance, blood and dialysate flow rates should be as high as possible, and the membrane with the largest surface area should be utilized. Intermittent hemodialysis is the most commonly employed extracorporeal procedure due to its highest effectiveness, while hemodynamically compromised patients can benefit from acontinuous procedure.

Application of Differential Equation in the Design of Dialysis Machine

In this work, I have discussed the application of differential equations in the design of a dialyzer machine. A dialyzer is a device through which blood flows from the patient's body into the machine. A substance called dialysate flows through the machine in the opposite direction to the blood. This aids in separating waste materials with the help of a semipermeable membrane attached to the machine. This membrane possesses minute pores that allow the passage of waste matter, which has much smaller molecules than the blood cells, but restrict the passage of blood itself. The design of the dialyzer machine concerns the flow rate of the waste material through the membrane. This flow-rate is determined by the differences in concentration of waste material on either side of the membrane, where, the flow occurs from high concentration to low concentration.

Significance of effluent dose in continuous renal replacement therapy in children

Abstract Continuous renal replacement therapy (CRRT) is one of the commonly used extracorporeal blood purification therapies and its use in the pediatric population has increased in the past two decades due to the availability of safer machines which allow lower blood flow rate and dialysate flow rate. The usual indication for initiation of CRRT is for solute clearance and or fluid removal in oliguric patients with acute kidney injury. Knowledge regarding the principles of solute removal and fluid removal along with the application of these mechanisms in different modes of CRRT helps the physician to decide on the appropriate therapy for the given patient. Understanding the concept of CRRT dose and the factors to be considered in the prescription for achieving the preset targets of CRRT is vital for the efficient utilization of the therapy.

The Effects of Early-Phase, Low- or Standard-Intensity Continuous Renal Replacement Therapy on Acid-Base Control and Clinical Outcomes: An Observational Study

Introduction: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline recommends administering an effluent volume of 20–25 mL/kg/h during continuous renal replacement therapy (CRRT) for acute kidney injury. Recent evidence on CRRT initiation showed that less intervention might be beneficial for renal recovery. This study aimed to explore the association between early-phase low CRRT intensity and acid-base balance corrections and clinical outcomes. Methods: This was a single-centre, retrospective, observational study at a tertiary intensive care unit (ICU) in Japan. All adult patients requiring CRRT in the ICU were included. Eligible patients were classified into the Low group (dialysate flow rate [QD] 10.0–19.9 mL/kg/h) and the Standard group (QD ≥20 mL/kg/h) by the intensity of CRRT at the beginning. The primary outcomes were acid-base parameters 6 h after CRRT initiation. We used an inverse probability of treatment weighting analysis to estimate the association between the intensity group and the outcomes. Results: Overall, 194 patients were classified into the Low group (n = 144) and the Standard group (n = 50). The Standard group presented with more severe acid-base disturbances, including lower pH and base excess (BE) at baseline. At 6 h after CRRT initiation, pH, BE, and strong ion difference values were comparable, even after adjusting for baseline severity. Despite the efficient correction, no evident differences were observed in clinical outcomes between the two groups. Conclusions: The initial standard intensity appeared to be efficient in correcting acid-base imbalance at the early phase of CRRT; however, further studies are needed to assess the impact on clinical outcomes.

The impact of dialysate flow rate on haemodialysis adequacy: a systematic review and meta-analysis.

Patients with kidney failure treated with maintenance haemodialysis (HD) require appropriate small molecule clearance. Historically, a component of measuring 'dialysis adequacy' has been quantified using urea kinetic modelling that is dependent on the HD prescription. However, the impact of dialysate flow rate on urea clearance remains poorly described in vivo and its influence on other patient-important outcomes of adequacy is uncertain. We searched Embase, MEDLINE and the Cochrane Library from inception until April 2022 for randomized controlled trials and observational trials comparing a higher dialysate flow rate (800ml/min) and lower dialysate flow rate (300ml/min) with a standard dialysis flow rate (500ml/min) in adults (age ≥18years) treated with maintenance HD (>90 consecutive days). We conducted a random effects meta-analysis to estimate the pooled mean difference in dialysis adequacy as measured by Kt/V or urea reduction ratio (URR). A total of 3118 studies were identified. Of those, nine met eligibility criteria and four were included in the meta-analysis. A higher dialysate flow rate (800ml/min) increased single-pool Kt/V by 0.08 [95% confidence interval (CI) 0.05-0.10, P<.00001] and URR by 3.38 (95% CI 1.97-4.78, P<.00001) compared with a dialysate flow rate of 500ml/min. Clinically relevant outcomes including symptoms, cognition, physical function and mortality were lacking and studies were generally at a moderate risk of bias due to issues with randomization sequence generation, allocation concealment and blinding. A higher dialysate flow increased urea-based markers of dialysis adequacy. Additional high-quality research is needed to determine the clinical, economic and environmental impacts of higher dialysate flow rates.

Does using a higher dialysate sodium concentration result in lower sodium losses with dialysis treatments?

IntroductionMany dialysis centres prescribe a uniform dialysate sodium (DialNa) concentration, but as there is no consensus on the choice of a universal DialNa, we wished to determine dialysate sodium balance comparing DialNa of 140 and < 140 mEq/L.MethodsWaste dialysate was continuously collected during sessions and thoroughly mixed, and sodium was measured in both the waste and fresh dialysate. Sodium removal was calculated as the difference in concentrations, dialysate flow rate, session time and ultrafiltration.ResultsDialysate sodium balance was measured during 139 dialysis treatments (34 DialNa 140 versus 105 DialNa < 140, median 136 mEq/L), in 111 patients, 63% male, mean age 64.0 ± 16.2 years and 33.3% diabetic. There was no difference using the higher DialNa [net loss median 482 (238–573) versus 312 (124–599) mEq], ultrafiltration losses [226 (131–280) versus 204 (125–290)mEq] and non-ultrafiltration losses [217 (0–384) versus 173 (−90 to 350)mEq]. We also compared haemodiafiltration and haemodialysis (118 versus 23 sessions), and there were no differences in net loss [311 (91–608) versus 381 (167–597)], ultrafiltration [212 (127–290) versus 169 (110–258)mEq] and non-ultrafiltration losses [180 (−51 to 386) versus 192 (−74 to 387)mEq].ConclusionsAlthough most dialysis centres prescribe a universal dialysate sodium concentration, there is no consensus on the optimum universal concentration. We found no difference in net dialysate sodium balance when comparing patients dialysing with a dialysate sodium concentration of 140 or < 140 mEq/L. Similarly, we found no differences in dialysate sodium balance between haemodiafiltration and haemodialysis sessions.

Hemodialysis Procedures for Stable Incident and Prevalent Patients Optimize Hemodynamic Stability, Dialysis Dose, Electrolytes, and Fluid Balance.

The demographic profile of patients transitioning from chronic kidney disease to kidney replacement therapy is changing, with a higher prevalence of aging patients with multiple comorbidities such as diabetes mellitus and heart failure. Cardiovascular disease remains the leading cause of mortality in this population, exacerbated by the cardiovascular stress imposed by the HD procedure. The first year after transitioning to hemodialysis is associated with increased risks of hospitalization and mortality, particularly within the first 90-120 days, with greater vulnerability observed among the elderly. Based on data from clinics in Fresenius Medical Care Europe, Middle East, and Africa NephroCare, this review aims to optimize hemodialysis procedures to reduce mortality risk in stable incident and prevalent patients. It addresses critical aspects such as treatment duration, frequency, choice of dialysis membrane, dialysate composition, blood and dialysate flow rates, electrolyte composition, temperature control, target weight management, dialysis adequacy, and additional protocols, with a focus on mitigating prevalent intradialytic complications, particularly intradialytic hypotension prevention.

Application of therapeutic ultrasonic waves across the dialyzer membrane: A pilot study on the impact on dialyzer clearance and safety.

Progressive clogging of the dialyzer membrane during hemodialysis can compromise solute removal efficiency. Existing solutions fall short in addressing intradialytic reduction of dialyzer clearance. This pilot study aims to assess the impact and safety of applying therapeutic ultrasonic waves to dialyzers for mitigating intradialytic clogging. In this pilot study, 15 stable maintenance hemodialysis patients (12 males and 3 females) were enrolled. Each patient served as their own control. They underwent one session of hemodialysis with the application of therapeutic ultrasonic waves (Ultrasonic session) and were crossed-over to a second session without the use of ultrasonic waves (Control session). All the study sessions operated at a fixed dialysate flow rate of 500 mL/min and a blood flow rate of 250 or 300 mL/min. The adequacy of dialysis achieved during each session was monitored using Online Clearance Monitoring of the dialysis machines, and clearance K values, varying between 135 and 209 mL/min, were recorded, and plotted. A direct comparison between Control and Ultrasonic sessions was performed to assess the impact and safety of using ultrasonic waves during hemodialysis. The mean percentage decline in dialyzer clearance values was 4.41% for Ultrasonic sessions (SD: 5.3) and 12.69% for Control sessions (SD: 6.35) (p-value <0.001). This indicates that the application of ultrasonic waves reduced the decline in clearance values. The mean differences of the blood component parameters were comparable between both Ultrasonic sessions and Control sessions, suggesting the safety of utilizing ultrasonic waves during dialysis. Microscopic membrane analysis corroborated the safety. Intradialytic clogging of dialyzer membranes is a significant problem that can cause dialysis inadequacy. Our study tackles this issue by introducing therapeutic ultrasonic waves to improve dialyzer clearance during hemodialysis sessions in patients.

#857 How low can we go with dialysate flow? Does that mean we can make nephrology green?

Abstract Background and Aims Green nephrology encompasses all initiatives in kidney care that have a positive impact on the climate and environment. We know that environmental impact of dialysis is particularly high, considering water consumption and disposable waste production during each session. All that suggests a great opportunity where many improvements should be made. To prepare the dialysate 240 liters of water are needed for one four-hour session with a dialysate flow (Qd) set at 500 ml/min. Including additional water needed to rinse and sterilize the system, this gives approximately 500 liters of water used for one hemodialysis. Lower dialysate flow rate is associated with a significant reduction in the amount of water used for the hemodialysis procedure. An increase in Qd from 500 ml/min to 800 ml/min has been recommended to increase dialysis efficiency. It's benefit was not confirmed in in vivo studies which suggested that increasing the dialysate flow rate offers no benefit in terms of delivered Kt/V. Similarly, studies with a Qd of 400 ml/min showed comparable efficiency. If hemodialysis could be performed equally effectively with less dialysate consumption, water could be significantly saved. The aim of this study was to check whether change of dialysate flow from 500 ml/min to 300 ml/min has a significant impact on dialysis adequacy (measured by Kt/V). Method The study was a retrospective analysis. During the COVID19 surge in January 2022 due to administrative issues in a satellite dialysis center the dialysate flow was reduced to 300 ml/min. The center again increased Qd to 500 ml/min in February 2022. We analyzed laboratory data from 3 months before dialysate flow reduction, in the month with reduced Qd to 300 ml/min, and from 3 months thereafter with Qd set at 500 ml/min. Results 26 patients (10 men and 16 women – all dialysis patients from a satellite dialysis center) were enrolled in the study. Two of them died during observation, therefore 24 people were included in final analysis. Their median age was 72 (66-78) years. ANOVA with repeated measures showed lack of differences between three time points in terms of Kt/V (Qd 500 ml/min - 1.285±0.202, Qd 300 ml/min - 1.275±0.192 and Qd 500 ml/min - 1.337±0.199; p=0.093). Change in serum potassium during hemodialysis did not depend on dialysate flow (ΔK Qd 500ml/min - 1.5±0.5 mmol/l, Qd 300 ml//min - 1.7±0.5 mmol/l, Qd 500 ml/min - 1.6±0.4 mmol/l; p=0.197). Serum phosphorus was comparable between three time points (Qd 500 ml/min - 5.99±1.68 mg/l, Qd 300 ml/min - 5.65±1.4mg/l, Qd 500 ml/min - 6.01±1.67 mg/l; p=0.066). Conclusion Reduction in dialysate flow rate to 300 ml/min is safe for the patients and probably does not cause any short-term negative effects. Thus we can achieve the same therapeutic effect saving water consumption. Larger, long-term studies are needed to confirm the efficacy of this approach.

#1094 Hemodiafiltration improves solute clearance without increasing water consumption: an educational bench model for the dialysis ward

Abstract Background and Aims Recently, the positive results of the CONVICE trial have raised the question whether the improved outcome of postdilution high volume HDF (oHDF-p) compared to high flux HD (hfHD) requires increased water consumption. From mathematical modelling it can be shown that oHDF-p always leads to higher low molecular clearance than hfHD at equal total dialysate consumption Qd_tot = Qd_dial + Qs (Qd_dial: dialysate flow through the dialyzer, Qs: substitution flow). This has also been shown in a clinical trial (Mesic et al, HDI 15, p. 522-529). However, mathematical modelling might not be intuitive for everyone, and clinical trials are always influenced by multiple confounders. To add a more intuitive way of reasoning, a simple educational bench model was designed based only on equipment easily available in a standard dialysis clinic which allows to compare dialysis efficiencies based on the urea concentrations as surrogate parameter. Since the fundamental task of dialysis is to cleanse blood from uremic solutes, the treatment modality which at equal resource utilization reduces solute concentration most is the more efficient one! Method Dialysis treatments were simulated in single pass setup using a Fresenius 5008S machine (Fig. 1). Blood inlet was simulated as a fixed urea concentration of 170 mg/dL in dialysate from a 110 L reservoir “cbi”. Treatment parameters were set such that they correspond to effective values in in-vivo treatments: As the mass transfer coefficient is always much higher in vitro with water than in vivo with blood, a small high-flux dialyzer (Fresenius FX40) was used. Blood flow Qb was set to 300 mL/min, corresponding to the in vivo blood water flow for Qb_set ∼ 350 mL/min. Alternating experiments in oHDF-p and hfHD were carried out in triplicate with Qd_tot=400 mL/min and 300 mL/min. This resulted in the settings HDF400, HD400, HDF300 and HD300 (cf. Fig. 1). Qs was set to 100 ml/min in oHDF-p. In each setting the fluid from blood and dialysate outlet were collected (recipients “cbo” and “cdo”, resp.) for 8 min. To be independent of the machine accuracy of set flow rates, sample volumes were measured by weighing, and effective flow rates of blood Qb_eff and total dialysate Qd_tot_eff were calculated. Samples were taken into monovettes from “cbi”, “cbo” and “cdo”. Urea concentrations cbi, cbo and cdo were determined by sending the samples to two commercial clinical labs who delivered consistent results. Blood and dialysate side urea clearances were calculated as KUB= Qb_eff*(cbi-cbo)/cbi and KUD=Qd_tot_eff*cdo/cbi. Results The table in Fig. 1 includes the measure values of Qb_eff and Qd_tot_eff for each setting. Blood and dialysate outlet concentrations (cbo and cdo, resp.) and calculated blood and dialysate side clearances are shown in Fig. 2. Lab results in repeated settings were highly reproducible with a SD &amp;lt; 2 mg/dL. Switching from hfHD to oHDF-p at equal Qd_tot always decreased cbo, corresponding to a higher clearance in oHDF-p. Reducing total dialysate flow from 400 to 300 ml/min caused a slight decrease in clearance in both modalities. KUB and KUD were in good agreement, showing that urea mass balance was well controlled in the experiment. Conclusion The educational bench model demonstrates the superior low molecular clearance of oHDF-p compared to hfHD at equal Qd_tot, reflected by lower urea cbo values in oHDF-p. Although the clinical outcome advantage of oHDF-p is rather related to middle molecular clearance, the model shows that the improved treatment quality of oHDF-p can be provided with no extra resource utilization compared to hfHD, and that dialysis adequacy as measured by urea clearance is even increased despite of the fact that a part of Qd_tot is deviated as substitution fluid. As moderately reducing Qd_tot in many cases only results in acceptable clearance reductions, the automated adjustment of both dialysate and substitution flow rates for oHDF-p could improve patient outcome at even reduced resource utilization.

#3064 Adequacy of urea and middle molecules clearance with online hemodiafiltration (HDF) for dialysate flow rates of 300 vs 500 ml/min

Abstract Background and Aims Trial cross design to determine non-inferiority in the adequacy of urea and middle molecules (B2 microglobulin, myoglobin and prolactin) clearance with 300 ml/min vs 500 ml/min of dialysate flow rate Method We have evaluated 2542 online HDF sessions (over 3 × 3 months trial cross design) in 50 patients in online HDF with sessions three times a week lasting 4 hours each. The online data from the DDM module of the Nikkiso DBB-EXA monitor were crossed, measuring urea in the dialysate effluent every 20 seconds by absorptiometry with UV light with age, sex, dialyzer, DM, BMI. In the laboratory, urea and B2 microglobulin, prolactin and mioglobin were measured at 300 and 500 ml/min, calculating the reduction rates of these toxins. We analyzed the data of 50 patients, in 25 patients, the first 3 months involved a dialysate flow rate 300 ml/min, followed by subsequent three months at 500 ml/min and vice versa for the remaining patients. They used the same dialyzer during the 3 × 3 months of the study as well as card programming. To study whether the change in dialysate flow influenced the effectiveness of dialysis, “generalized models with repeated measurements over time correcting the temporal autocorrelation with the covariance matrix AR1” were used the following parameters: kt/v, eKt/V and URR Results 23 men, 27 women, average age 70 years Kt/V.- The variables that are related to the Kt/v values throughout the sessions are: The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta = 0.01, 95% CI (−0.06, 0.08),p0.707 The effective gender (female) is statistically significant and positive (beta = 0.26, 95% CI (0.15, 0.38) p &amp;lt; 0.001 The effect of DM is statistically non-significant and negative (beta = −0.1, 95% CI (−0.22, 0.01) p = 0.081 The effect of period 2 is statistically non-significant and negative (beta = −0.02, 95% CI (−0.08, 0.03) p = 0.37 eKt/V.- The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta = 0.05, 95% CI (−0.02, 0.12),p0.138 The effect gender (female) is statistically significant and positive (beta = 0.22, 95% CI (0.11, 0.33) p &amp;lt; 0.001 The effect of DM is statistically non-significant and negative (beta = −0.10, 95% CI (−0.20, 0.01) p = 0.082 The effect of period 2 is statistically non-significant and negative (beta = −2.44e.03, 95% CI (−0.06, 0.05) p = 0.930 URR.- The effect of dialysate Flow 500 ml is statistically non-significant and positive (beta=1.19, 95% CI (−0.22, 2.60),p0.098 The effect of gender (female) is statistically significant and positive (beta=5.52, 95% CI (3.48, 7.56) p &amp;lt; 0.001 Didn´t found significant difference between mean of RRb2 microglobulin, RRProlactin and RRMioglobin with dialysate flow 300 vs 500 ml/min Conclusion Urea and B2 microglobulin, myoglobin and prolactin depuration is adequate at both dialysate flow rate 500 ml/min and 300 ml/min in the evaluated patients.

#2548 In vitro evaluation of proenkephalin kinetics in hemofiltration and hemodialysis

Abstract Background and Aims Proenkephalin A 119-159 (penKid) is a stable surrogate marker for enkephalins (endogenous opioids regulating kidney function). PenKid plasma concentration correlates to GFR and increases in AKI, for this reason it can be used for prediction and diagnosis of AKI (even subclinical forms) and need of RRT. Furthermore, it seems to be also a reliable biomarker to predict the successful liberation from RRT and may therefore aid in the successful weaning of patients from RRT. PenKid has the perk of maintaining stable its concentration during RRT, suggesting that is barely filtered, in contrast to other biomarkers. However, with its small size of 4.5 kDa, penKid can be assumed to be freely filtered through the glomerulus and dialysis membranes. To address the issue about stable penKid plasma concentrations in RRT (no extracorporeal removal or increased production in response to impaired kidney function), we planned ex vivo experiments simulating different conditions of RRT. The aim of this study is to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively. Method The lyophilized peptide was solved in 20 mM Dipotassium phosphate, 6 mM Disodium EDTA [pH 8], avoiding concentrations higher than 1 mg/mL. The compound was diluted in 50 mL of plasma to ensure homogeneous distribution. For each experimental modality, a batch of blood of 1000 mL with adjusted hematocrit at 30% and albumin concentration of 3 g% was utilized. Blood was spiked with lyophilized synthetic penKid to achieve two target concentrations of 150 and 500 pmol/L in CVVH and CVVHD modalities, respectively. Blood was adjusted for a volume of 1000 mL, maintained at 37° and continuously stirred during the experiments. CVVH was performed with blood flow (QB) = 150 mL/min and ultrafiltration rate (QUF) = 20 mL/min to reproduce a filtration fraction of 20%. The ultrafiltrate was reinfused in the venous line to maintain initial volume. This allowed to define convective clearance and solute sieving coefficient in pure convective mode. CVVHD was performed with QB = 150 mL/min and dialysate flow (QD) = 35 mL/min (Net QUF = 0 mL/min). This allowed the calculation of diffusive clearance. A polysulfone dialyzer (AV1000 FMC, Bad Homburg, Germany) was utilized. Samples were taken at 10, 30, 60 minutes from the initiation of the circulation, in both modalities. Results Initial penKid concentrations in blood corresponded to the desired targets in all the experiments. Sieving coefficients displayed values between 0.69 and 1.5 and they appear to remain stable over time (Fig. 1). Diffusive clearance displayed values between 35 and 15.7 mL/min. Values appear to present a slight decrease over time (Fig. 2). The observed variability can be attributed to several factors: difference in plasma protein interference in various moments of the experiments, difference in concentration of penKid in plasma water versus plasma or blood, variability in the sample measurements. Conclusion Significant removal of penKid can be obtained by extracorporeal therapies both in convection (CVVH) and diffusion (CVVHD). Further investigation is needed to assess if these findings are confirmed during in vivo treatments in which penKid kinetics is affected by generation, elimination and changes in distribution volume.

#828 Non-invasive determination of uric acid in blood during hemodialysis with an optical spent dialysate sensor

Abstract Background and Aims Kt/V urea is conventionally used hemodialysis (HD) adequacy marker, whereas many other uremic toxins with differing removal kinetics affect the mortality of end stage kidney disease (ESKD) patients. Among them, uric acid (UA) has been shown to cause cardiovascular mortality of ESKD patients. Recently, determination of UA concentration in blood with optical sensors during HD has been attempted by Lin et al in 2021 and Żyłka et al in 2023, but the accuracy has been relatively low. Moreover, Żyłka et al measured light absorption of spent dialysate at 573 nm to determine UA concentration, whereas previous research has shown that dialysate and UA have negligible light absorption in that region. The aim of this observational study was to predict concentration of UA with higher accuracy in ESKD patients’ blood during HD with various treatment settings by monitoring spent dialysate noninvasively with an optical sensor. Method Twenty-two ESKD patients on chronic HD were included into the study. Each patient received four 4 h long midweek HD sessions: one standard HD and three haemodiafiltration (HDF) sessions with different settings. Median (interquartile range) settings of the 1 HD session were: effective blood flow (Qb) = 199 (198-199) mL/min, dialysate flow (Qd) = 297 (297-298) mL/min, ultrafiltration rate (UF) = 13 (8-16) mL/min, dialyzer area 1.5 m2 and for the 3 HDF sessions: Qb = 298 (296-356) mL/min, Qd = 788 (489-792) mL/min, substitution fluid flow (Qsubs) = 96 (66-106) mL/min, UF = 11 (8-15) mL/min, dialyzer areas 1.8 m2 and 2.2 m2. Blood samples were collected before the start and at the end of each HD session from the arterial blood line and spent dialysate samples were collected 7, 60, 120, 180 and 240 min after the start from the outlet of the HD machine. Concentration of UA in spent dialysate and serum samples were determined with HPLC. An optical sensor (Optofluid Technologies OÜ, Tallinn, Estonia) was connected to the spent dialysate outlet of the HD machine and ultraviolet (UV) light absorption of spent dialysate was measured online in real time for each HD session. A linear interactions regression model was created using light absorbance at four different UV wavelengths to predict UA concentrations in collected spent dialysate samples. A curve of UA concentration for the whole HD session was determined based on the model and UV absorbance data measured with the optical sensor. Thereafter, UA concentration in spent dialysate at the start and at the end of each session (UAsensor hereinafter) was found from the concentration curve. The data of 88 HD sessions were equally divided into calibration and validation sets. Linear regression model was created using data of calibration set to predict concentration of UA (UApredicted) in blood as follows: UApredicted = a • UAsensor • $\frac{{{\rm{Qd}} + {\rm{\ Qsubs}} + {\rm{UF\ }}}}{{{\rm{Qb}}}}$, where “a” is the slope, UAsensor is the UA concentration in spent dialysate found from the concentration curve of the optical sensor, Qb is effective blood flow and Qd+Qsubs+UF is the total flow of spent dialysate. Subsequently, the accuracy of the model was evaluated on the calibration and validation data using Bland Altman analysis. Results UA concentrations in spent dialysate determined with HPLC and estimated with the optical sensor were strongly correlated (R2 = 0.992) and with comparable accuracy (BIAS±SE) (0.1 ± 3.84) µmol/L. Coefficient of determination 0.951 with the accuracy of 0.00 ± 31.43 µmol/L was achieved for calibration group, and coefficient of determination 0.962 with the accuracy of −7.64 ± 32.06 µmol/L was achieved for validation group between the UA concentration in blood determined with HPLC and corresponding values predicted by the optical sensor, respectively (Fig. 1). Conclusion Concentration of UA in dialysate and blood can be estimated noninvasively and accurately with the optical sensor in real time. This can be used to estimate removal efficiency and levels of UA during HD. In future, removal of other uremic toxins could be additionally monitored leading to a more personalized HD treatment.

#3022 Rationale and design of the CORDIAL first-in-human clinical trial: a system for sorbent-assisted continuous flow peritoneal dialysis

Abstract Background and Aims Peritoneal dialysis has important disadvantages, including low plasma clearance and a limited technique survival. A new device for sorbent-assisted continuous flow peritoneal dialysis has been designed (Wearable Artificial KIDney, WEAKID) that is based on continuous recirculation (rapid cycling) of peritoneal dialysate via a single-lumen peritoneal catheter with regeneration of dialysate using sorbents. Anticipated benefits are a better plasma clearance a higher mass transfer area coefficient with continuous flow of dialysate and enhanced diffusion due to a higher time-averaged plasma-dialysate concentration gradient with sorbent-based dialysate regeneration, and a prolonged technique survival thanks to lower peritonitis risk (less (dis)connections) and a lower glucose exposure. Method This is a first-in-human, prospective, open-label, non-randomized, single-arm, multicenter study, that will be performed at the University Medical Center Utrecht (Utrecht, The Netherlands), Università degli studi di Modena e Reggio Emilia (Italy), and Instituto de Investigación Hospital Universitario La Paz, Servicio Madrileño de Salud (Spain). We aim to include 12 stable, adult PD patients. In the first week, blood, urine, and dialysate samples will be collected over three separate days to assess the efficacy of the patient's standard PD schedule. The WEAKID system will then be tested in a clinical setting on 6 days over a period of 2 weeks (three consecutive days per week). During the first week, participants will be treated with WEAKID without sorbents for 4h (first day) or 8h (second and third day). The second week, treatment will consist of WEAKID with sorbents for 4h (first day) or 8h (second and third day). This way, exposure to new components of the system is incremental and the effectiveness of continuous recirculation of dialysate and that the added effect of sorbent-based dialysate regeneration can be analyzed separately. Outcomes The primary aim of this first-in-human clinical trial is to evaluate the (short term) clinical safety and performance of WEAKID treatment in a clinical setting. The primary safety objective will be assessed by describing and examining the incidence of: Key secondary objectives include an evaluation of efficacy in terms of plasma clearance, ultrafiltration, net base release, and patient tolerance. Planning Inclusion of the first patient is expected in January 2024, the final inclusion is expected to take place in November 2024.