Ultrafiltration Volume Research Articles

Basic physics of hemodiafiltration.

Standard high-flux hemodialysis (HD) clears urea very efficiently but is less efficient at clearing uremic toxins with larger molecule size, which diffuse more slowly. Hemodiafiltration (HDF) provides much higher convection rates, thereby reliably increasing the clearance of these larger toxins. However, the high ultrafiltration volumes employed by HDF significantly increase the concentration of proteins and lipids in the dialyzer blood compartment. This has the effect of increasing plasma viscosity, which opposes solute diffusion, and increasing plasma oncotic pressure, which opposes convection. The negatively charged plasma proteins also influence the equilibration of ions between dialysate and blood compartments. These effects result in varying conditions for solute transport along the length of the dialyzer and along the radial distance from the membrane within the dialyzer fibers. High-flux dialyzers can be designed to augment solute diffusion and internal filtration, so that their performance approaches that of HDF. This avoids some of the mechanical complexity of HDF, but such enhanced dialyzers may be more difficult to manufacture, control and monitor. Here, we present and discuss the most important physical phenomena associated with HDF therapy, providing an overview of its main concepts and principles. In particular, we discuss the physics of solute diffusion and convection and the factors affecting them, and we compare predilution or postdilution HDF with enhanced HD.

The benefits of initiating continuous renal replacement therapy after brain death in organ donors with oligoanuric acute kidney injury

Acute kidney injury (AKI) in deceased organ donors is increasing due to the escalation in anoxic brain-deaths. The management of an organ donor with oligoanuric AKI is frequently curtailed due to hemodynamic and electrolyte instability. Although continuous renal replacement therapy (CRRT) corrects the effects of AKI, it is rarely started after the diagnosis of brain-death (BD). Since 2017, we have initiated CRRT in organ donors with oligoanuric AKI to allow more time to stabilize the donor and improve the function of the thoracic organs. We now report our experience with the first 27 donors with oligoanuric AKI that received CRRT after the diagnosis of BD, with organs transplanted as the primary outcome. The average duration of CRRT was 30.1±14.4h and the mean ultrafiltration volume was 5141±4272 ml. The time from BD declaration to cross clamp was significantly longer in the CRRT group versus a historical cohort with oligoanuric AKI that was not dialyzed (62.8±18.3vs. 37.1±14.9h; P<.01). The mean number of total organs transplanted per donor in the CRRT group was greater than the historical cohort, 2.9±1.7vs. 1.4±.6 (P=.<01), respectively. The mean number of thoracic organs transplanted per donor also increased between the two groups, 1.4±1.2versus .6±.9 (P=.02). Thirty-seven percent of the kidneys were successfully transplanted with a mean serum creatinine of 1.4mg/dl at 6months. We suggest that OPOs consider starting CRRT in organ donors with oligoanuric AKI to possibly increase the number of organs transplanted.

Measurement of peritoneal fluid absorption and ultrafiltration during peritoneal dialysis using segmental bioimpedance.

The aim of this study was to measure intraperitoneal volume (IPV) and ultrafiltration volume (UFV) by monitoring the abdominal resistance using segmental bioimpedance analysis (SBIA, Hydra 4200). Twenty peritoneal dialysis (PD) patients were studied during a fill with 2 L of 2.5% glucose peritoneal dialysate solution. UFVDrain (g) was measured as weight difference between fill and drain dialysate volumes. Ultrafiltration volume (UFVSBIA; ml) and absorption volume were calculated from the IPV curve derived by SBIA. UFVSBIA correlated with UFVDrain ( ). This study may provide actionable clinical insights and help clinicians to better understand the function of the peritoneal membrane in individuals. Clinical Relevance-This technique may support personalized medicine by aiding the prescription of PD therapy on a patient-level.

Optimization of the Chronic Kidney Disease-Peritoneal Dialysis App to Improve Care for Patients on Peritoneal Dialysis in Northeast Thailand: User-Centered Design Study.

BackgroundThe prevalence of peritoneal dialysis (PD) in Thailand is increasing rapidly in part because of Thailand’s Peritoneal Dialysis First policy. PD is a home-based renal replacement therapy in which patients with chronic kidney disease perform up to 4 exchanges of dialysate fluid per day in the peritoneal cavity. Overhydration is one of the most common complications in patients on PD and is associated with increased morbidity and mortality. To monitor hydration status, patients collect hydration metrics, including body weight, blood pressure, urine output, and ultrafiltration volume, from each dialysis cycle and enter this information into a PD logbook. This information is reviewed bimonthly at PD clinic appointments. The chronic kidney disease-PD (CKD-PD) app with near-field communication (NFC) and optical character recognition (OCR) was developed to automate hydration metric collection. The information was displayed in the app for self-monitoring and uploaded to a database for real-time monitoring by the PD clinic staff. Early detection and treatment of overhydration could potentially reduce the morbidity and mortality related to overhydration.ObjectiveThis study aims to identify usability issues and technology adoption barriers for the CKD-PD app with NFC and OCR and a monitoring system and to use this information to make rapid cycle improvements.MethodsA multidisciplinary team of nephrologists, PD clinic nurses, computer programmers, and engineers trained and observed 2 groups of 5 participants in the use of the CKD-PD app with NFC and OCR and a monitoring system. The participants were observed using technology in their homes in 3 phases. The data collected included the Unified Theory of Acceptance and Use of Technology questionnaire, think-aloud observation, user ratings, completion of hydration metrics, and upload of hydration metrics to the central database. These results were used by the team between phases to improve the functionality and usefulness of the app.ResultsThe CKD-PD app with NFC and OCR and a monitoring system underwent 3 rapid improvement cycles. Issues were identified regarding the usability of the NFC and OCR data collection, app stability, user interface, hydration metric calculation, and display. NFC and OCR improved hydration metric capture; however, issues remained with their usability. App stability and user interface issues were corrected, and hydration metrics were successfully uploaded by the end of phase 3. Participants’ scores on technology adoption decreased but were still high, and there was enthusiasm for the self-monitoring and clinical communication features.ConclusionsOur rapid cycle process improvement methodology identified and resolved key barriers and usability issues for the CKD-PD app with NFC and OCR and a monitoring system. We believe that this methodology can be accomplished with limited training in data collection, statistical analysis, and funding.

An Analysis on the Clinical Features of Maintenance Hemodialysis Patients with Coronavirus Disease 2019: A Single Center Study

Background and Objectives:Patients on maintenance hemodialysis (MHD) are at high risk for coronavirus disease 2019 (COVID-19). However, patients undergoing MHD who are infected with COVID-19 are not fully studied. The objective of this study is to describe the characteristics of patients with COVID-19 undergoing MHD and provide a basis for the recognition and prevention of COVID-19 infection.Materials and Methods:Patients undergoing MHD were assigned into the normal group (537 cases), diagnosed group (66 cases), and suspected group (24 cases). General data, clinical symptoms, hemodialysis indicators, and laboratory indicators were collected and compared.Results:A total of 627 patients undergoing MHD were evaluated. The prevalence of COVID-19 was 10.53% (66/627), mortality was 18.18% (12/66), and death rate was 1.91% (12/627). In addition, 26% of patients were asymptomatic. Cough was the most common symptom (36%), followed by fatigue (16%), dyspnea (16%), and fever (13%). Ultrafiltration volume, ultrafiltration rate, and the duration of weekly dialysis in the diagnosed group were significantly lower than those in the other two groups. Moreover, neutrophil ratio and neutrophil, monocyte, and total carbon dioxide levels in the diagnosed group were significantly higher than those in the normal group, and the lymphocyte ratio was considerably lower than in the normal group. Sixty-five of the suspected and diagnosed patients had positive pulmonary CT findings.Conclusion:Compared with the general population, patients on hemodialysis have a significantly higher risk of contracting COVID-19 and postinfection mortality. Moreover, most patients undergoing hemodialysis have no obvious clinical symptoms after infection with COVID-19 but only have pulmonary changes which make it particularly important to screen and manage patients undergoing hemodialysis on outpatient basis.

Dynamics of vascular refilling in extended nocturnal hemodialysis.

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 (7h) nocturnal treatment sessions. Specific UF rate was 4.8 ± 1.8ml/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 4h 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 (Rbex ) was 0.306 ± 0.029 before and slightly but significantly increased to 0.326 ± 0.030 after UF. In 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.

A Clinically Relevant Murine Model of Peritoneal Fibrosis by Dialysate and Catheters.

Peritoneal fibrosis can occur in patients undergoing peritoneal dialysis (PD), and patients with severe peritoneal fibrosis have high morbidity and mortality. Peritonitis, high-glucose peritoneal dialysis fluid, and a long period of PD precipitate the onset of peritoneal fibrosis. An animal study of peritoneal fibrosis is needed due to the limitations of human and in vitro studies. However, most animal models do not mimic clinical conditions. To study peritoneal fibrosis, we developed a clinically relevant murine model by implanting a peritoneal catheter and injecting 2.5% high-glucose PD fluid plus 20 mM methylglyoxal (MGO) into the peritoneal cavity daily for 21 days. Implantation of the peritoneal catheter avoids peritoneal injury by needles and mimics clinical PD patients. Immunofluorescence staining showed that myofibroblasts accumulated in the fibrotic peritoneum. The experimental group had lower ultrafiltration volume and peritoneal membrane transport function (peritoneal equilibration test). In this article, we provide a detailed protocol of the model.

Sex Modulates Cardiovascular Effects of Icodextrin-Based Peritoneal Dialysis Solutions.

Background/Aims: Some previous observations have noted that after six months of peritoneal dialysis (PD) treatment with icodextrin solutions, blood pressure (BP) and NT-proBNP tend to return to baseline values. This may be due to accumulation of icodextrin products that exert a colloid osmotic effect, which drives water into the bloodstream, causing the rise in blood pressure. Since icodextrin is metabolized by α-Amylase and its gene copies are lower in females than in males, we hypothesized icodextrin metabolites reach higher concentrations in females and that cardiovascular effects of icodextrin are influenced by sex. Methods: Secondary analysis of a RCT comparing factors influencing fluid balance control in diabetic PD patients with high or high average peritoneal transport receiving icodextrin (n = 30) or glucose (n = 29) PD solutions. Serum icodextrin metabolites, osmolality, body composition and Inferior Vena Cava (IVC) diameter were measured at baseline, and at 6 and 12 months of follow-up. Results: After six months of treatment, icodextrin metabolites showed higher levels in females than in males, particularly G5-7 and >G7, serum osmolality was lower in females. In spite of reduction in total and extracellular body water, ultrafiltration (UF) was lower and IVC diameter and BP increased in females, suggesting increment of blood volume. Conclusion: Females undergoing PD present with higher levels of icodextrin metabolites in serum that may exert an increased colloid-osmotic pressure followed by less UF volumes and increment in blood volume and blood pressure. Whether this could be due to the lesser number of α-Amylase gene copies described in diabetic females deserves further investigation.

MO683: Peritoneal Transport Characteristics, Sodium Sieving and Dialysate Electrolyte Clearance in Peritoneal Dialysis Patients: 4.25% Peritoneal Equilibration Test Analysis

Abstract BACKGROUND AND AIMS Peritoneal dialysis (PD) is a well-established renal replacement therapy for patients with end-stage renal disease. The peritoneal equilibration test (PET) is widely used for assessing peritoneal solute transport. Recently, the International Society for PD committee recommended performing PET with 4.25% dextrose solution instead of traditional 2.5% dextrose solution to provide better information on ultrafiltration capacity. This study aims to explore the peritoneal transport characteristics, sodium sieving and electrolyte clearance with PET-4.25%. METHOD We conducted a cross-sectional study in PD patients treated in West China Hospital between June 2021 and December 2021. All patients underwent PET-4.25%. Peritoneal transport characteristics, sodium sieving and dialysate electrolyte clearance were analysed. RESULTS A total of 108 patients (61 males, 56%; mean age 48 ± 4 years old, median PD duration 17 months) were included. Dialysate to plasma (D/P) creatinine values at 4 h were distributed similarly in PET-2.5% and PET-4.25% (Fig. 1). The dialysate sodium decreased at the beginning of PET-4.25% and gradually increased, while other dialysate electrolyte levels continued to increase or decrease during the 4 h (Fig. 2). Most patients had their maximal sodium dip at 2 h (N = 80, 74%). The mean sodium dip at 1 h was 7.28 ± 2.93 mmol/L (sodium sieving ratio 0.057 ± 0.023), and the mean maximal sodium dip was 8.81 ± 4.18 mmol/L. In both univariate and multivariate analyses, sodium sieving was negatively correlated with 4-h D/P creatinine and glomerular filtration rate (GFR) and positively correlated with PET-4.25% ultrafiltration volume (Fig. 3). The total clearances of sodium, potassium, chloride, calcium, magnesium and phosphate with 2 L of 4.25% dextrose were 66.9 ± 22.4 mmol, 6.64 ± 1.25 mmol, 62.7 ± 27.7 mmol, 0.07 ± 0.27 mmol, 0.63 ± 0.19 mmol and 1.98 ± 0.63 mmol, respectively. The amount of electrolyte clearance was not related to peritoneal transport characteristics. Nine patients were diagnosed with ultrafiltration failure (UFF). Patients with UFF had significantly lower sodium and chloride clearance than non-UFF patients. CONCLUSION PET-4.25% could assess peritoneal transport characteristics with similar results to PET-2.5%, while it could provide more information on ultrafiltration capacity. Four-hour D/P creatinine, GFR and ultrafiltration volume are independent predictors for sodium sieving. Dialysate electrolyte clearance is not related to peritoneal transport characteristics, while sodium clearance is decreased in UFF patients.

MO651: The Blood to Extracellular Volume Relationship is Stable and in the Physiologic Range in Chronic Haemodialysis Patients

Abstract 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 &amp;lt; .001) between BV and ECV both at the beginning (r = 0.88) and at the end (r = 0.88) of dialysis. 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.

Detecting Volemic, Cardiac, and Autonomic Responses From Hypervolemia to Normovolemia via Non-Invasive ClearSight Hemodynamic Monitoring During Hemodialysis: An Observational Investigation.

Background: Unstable hemodynamics are not uncommon during hemodialysis (HD), which involves a rapid volume depletion, taking the patient from hypervolemia toward euvolemia. Since uremic patients commonly have cardiovascular comorbidities, hemodynamic changes during HD may reflect interactions among the volemic, cardiac, and autonomic responses to gradual volume depletion during ultrafiltration. Accurate identification of inappropriate responses helps with precisely managing intradialytic hypotension. Recently, the non-invasive ClearSight was reported to be able to detect causes of intraoperative hypotension. In this prospective observational study, we aimed to determine whether ClearSight could be used to detect patterns in stroke volemic, cardiac, and vasoreactive responses during HD. Methods: ClearSight was used to monitor chronic stable patients receiving maintenance HD. Data of mean arterial blood pressure (MAP), heart rate (HR), stroke volume index (SVI), cardiac index (CI), and calculated systemic vascular resistance index (SVRI) were obtained and analyzed to examine patterns in volemic, cardiac, and vasoreactive changes from T0 (before HD) until T8 in 30-min intervals (total 4 h). Results: A total of 56 patients with a mean age of 60.5 years were recruited, of which 40 of them were men. The average ultrafiltration volume at T8 was 2.1 ± 0.8 L. The changes in MAP and HR from T0 to T8 were non-significant. SVI at T7 was significantly lower than that at T1, T2, and T3. CI at T4 to T8 was significantly lower than that at T0. SVRI was significantly higher at T3 to T8 than at T0. Pearson’s correlation coefficients between SVI and CI and between SVRI and MAP were positive at all time points. The correlation coefficients between SVRI and SVI and between CI and SVRI were significant and negative for all time points. Conclusion: ClearSight was able to detect patterns in hypervolemia during HD and was well tolerated for 4 h. CI decreased significantly after T4, with slightly decreased SVI. Ultrafiltration volume was not correlated with changes in SVI or CI. The vascular tone increased significantly, and this counteracted the reduced cardiac output after T4. With simultaneous monitoring on SVI, CI, and SVRI during HD, therefore, hypotension could be detected and managed by reducing the filtration rate or administering inotrope or vasopressors. Trial Registration: clinicaltrials.gov, ID: NCT03901794.

Coronary artery calcification is a risk factor for intradialytic hypotension in patients undergoing hemodialysis.

We investigated the association between intradialytic hypotension (IDH) and coronary artery calcification and their effects on mortality in hemodialysis (HD) patients. Consecutive patients undergoing maintenance HD were enrolled. The study timeline included the baseline (day 1), exposure assessment (day 1-day 22), and outcome assessment (day 23-3 years) periods. IDH was defined as a nadir systolic blood pressure (SBP) of <100 mmHg or vasopressor use during at least 2 of 10 HD sessions in the exposure assessment period. The clinical data at baseline and the Agatston coronary artery calcium score (CACS) were assessed in the exposure assessment period. The median age and dialysis vintage were 67 years [60-75 years] and 73 months [37-138 months], respectively. IDH occurred in 37 patients (21.4%), and the CACS was higher in the IDH group than in the non-IDH group (p=0.08). IDH was associated with CACS, diabetes mellitus, mean predialysis SBP, and mean ultrafiltration volume (p < 0.05). The cutoff CACS for mortality was 1829 (sensitivity: 69%, specificity: 77%). In all, 45 all-cause deaths and 19 cardiovascular deaths occurred over 3 years. Patients with both IDH and a CACS of ≥1829 had a lower 3-year cumulative survival from cardiovascular death (66.7%) than those with a CACS of ≥1829 (80.3%), IDH (88.5%), or neither (95.5%) (p < 0.01). IDH, a CACS of ≥1829, and IDH + CACS of ≥1829 were predictors of 3-year all-cause and cardiovascular mortality (p < 0.05). The hazard ratio for cardiovascular mortality was highest in the group with IDH + CACS ≥ 1829. A high CACS may be a biomarker for IDH. Both IDH and CACS were risk factors for all-cause and cardiovascular mortality in patients undergoing HD, and there was a synergistic interaction between IDH and high CACS for cardiovascular mortality.

Effects of a remote patient monitoring system for patients on automated peritoneal dialysis: a randomized crossover controlled trial.

PurposeRemote patient monitoring (RPM) has contributed to improved patient-centered outcomes and prognosis in patients with end-stage renal disease on automated peritoneal dialysis (APD). However, evidence from prospective trials is lacking.MethodsThe participants (n = 15; median age: 65 years; males: 10; peritoneal dialysis vintage: 6.4 ± 3.5 years) randomly received APD therapy using the Kaguya® APD system either with or without the connective use of the cloud-based RPM software Sharesource® for 12 weeks. The primary outcome was patient satisfaction assessed using a modified nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) questionnaire. The secondary outcomes were healthcare resource consumption, the health-related quality of life (HRQOL) subscales assessed with the Kidney Disease Quality of Life-Short Form questionnaire, and clinical laboratory parameters.ResultsSignificant improvements were observed in the TSQM-9 subscales of Effectiveness (64.4 ± 18.8 vs. 57.8 ± 18.8; P = 0.006) and Convenience (76.3 ± 15.4 vs. 63.3 ± 17.3; P < 0.001) in patients on Sharesource®. Moreover, Sharesource® reduced the total amount of healthcare resource consumption (0.80 ± 1.32 vs. 1.87 ± 2.39 times/12 weeks; P = 0.02) and consultation time during regular monthly visits (813 ± 269 vs. 1024 ± 292 s; P < 0.001). A significant increase in ultrafiltration volume was found associated with more frequent modification of APD prescription in patients with Sharesource®. Sharesource® also improved the HRQOL subscale of General Health and Vitality.ConclusionSharesource® can improve patient-centered outcomes in patients on APD while reducing the treatment burden for both patients and medical staff.Trial registration: The study was registered in the Japan Registry of Clinical Trials (jRCT Number: jRCTs032190005).Supplementary InformationThe online version contains supplementary material available at 10.1007/s11255-022-03178-5.

Peritoneal dialysis effluent-derived exosomal miR-432-5p: an assessment tool for peritoneal dialysis efficacy.

BackgroundUltrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR-432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR).MethodsThe PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR >0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells.ResultsOur results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=−0.376; P<0.05; n=40) and 4 h DSR (r=−0.535; P<0.01; n=24). Epithelial sodium channel α subunit (α-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDE-exo could be internalized into MeT-5A cells.ConclusionsA high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating α-ENaC expression.

Fluid balance assessment in pediatric hemodialysis patients by using whole-body bioimpedance spectroscopy (WB-BIS).

Fluid overload is a major factor in morbidity and mortality in dialysis patients. Whole-body bioimpedance spectroscopy (WB-BIS) is a noninvasive method for assessing fluid status. We hypothesized that fluid status measurement of changes in total body water (TBW), extracellular fluid (ECF), and intracellular fluid (ICF) by WB-BIS would correlate with the weight (Wt) changes before and after hemodialysis (HD) and the amount of ultrafiltration (UF) in pediatric HD patients. We also examined the relationship between the ECF percent of total body water (ECF%) and ECF/ICF ratio with the pre-HD systolic blood pressure percentile (SBP%ile). WB-BIS measurements were made both before and after HD on three separate occasions in each patient. Pre- and post-HD Wt, BP, and UF volumes were collected on the day of BIS measurement. At total of 96 measurements were obtained from 16 HD patients. There were 6 females (mean age: 13.2 ± 4.5 yrs). UF correlated with changes in weight, TBW and ECF (p < 0.001) but not with ICF changes (p = 0.345). Pre-HD SBP%ile correlated with ECF%. Our findings suggest that WB-BIS can be used to monitor the fluid status in pediatric HD patients. The fluid that is removed from the patient during the HD treatment primarily comes from the ECF and not the ICF. Mobilization of fluid from the ICF appears to be delayed. Patients with significantly higher pre-HD ECF% and ECF/ICF ratio had higher pre-HD systolic BP. A higher resolution version of the Graphical abstract is available as Supplementary information.

POS-689 APPLICATION OF AN ADVANCED ULTRAFILTRATION MANAGEMENT SYSTEM USING AWAK SORBENT-BASED PERITIONEAL DIALYSIS IN A PORCINE MODEL

In sorbent-based peritoneal dialysis (PD), spent dialysate is processed continuously and the regenerated dialysate is reconstituted with glucose, calcium and magnesium before returning to the patient’s peritoneum. Glucose infusion allows steady and sustained ultrafiltration (UF) production. Ultrafiltration requirements vary from patient to patient and in standard-of-care (SOC) PD modalities, targeted daily ultrafiltration volume can be regulated by controlling the concentration of dialysis solutions used.

Impact of the nature of the capillary wall on plasma refilling during hemodialysis.

Our aim was to clarify the impact of the nature of the capillary wall, defined by the contribution of large (LP), small (SP), and ultrasmall (UP) pores, on plasma refilling in a hemodialysis session. This study included data from 78 patients. The relative blood volume change (ΔBV%) was monitored using a Crit-Line monitor. A bioimpedance device was used to measure extracellular and intracellular fluid volumes, and the excess fluid mass (MExF) was calculated. We simulated blood volume change (sΔBV%) based on a three-pore model. Hydraulic permeability of the capillary wall (LpS) and fractional contribution of LP to LpS (αLP) were determined by fitting sΔBV to ΔBV. The total refilling volume (TVref) was calculated from the total ultrafiltration volume and total blood volume change. Values were standardized to a body surface area of 1.73 m2 and are denoted by the subscript BSA. LpS and αLP were 3.09 (2.32, 4.68) mL/mmHg/min and 0.069 (0.023, 0.109), respectively. The standardized regression coefficient (β) of the ultrafiltration rate (UFRBSA) and initial excess fluid mass (MExF,BSA,0) by multiple linear regression analysis of TVref,BSA without (Model 1) and with (Model 2) αLP were as follows: UFRBSA, 0.714/<0.001 (β/p); MExF,BSA,0, 0.247/<0.001 (Model 1); UFRBSA, 0.799/<0.001; MExF,BSA,0, 0.066/0.237; and αLP, -0.327/<0.001 (Model 2). The impact of volume overload (MExF,BSA,0) on plasma refilling became insignificant with the addition of αLP in the model, suggesting that the nature of the capillary wall described by inter-endothelial gaps (LP) may have a greater impact on plasma refilling than volume overload.

Proportional integral feedback control of ultrafiltration rate in hemodialysis

Most hemodialysis patients without residual kidney function accumulate fluid between dialysis session that needs to be removed by ultrafiltration. Ultrafiltration usually results in a decline in relative blood volume (RBV). Recent epidemiological research has identified RBV ranges that were associated with significantly better survival. The objective of this work was to develop an ultrafiltration controller to steer a patient's RBV trajectory into these favorable RBV ranges. We designed a proportional-integral feedback ultrafiltration controller that utilizes signals from a device that reports RBV. The control goal is to attain the RBV trajectory associated with improved patient survival. Additional constraints such as upper and lower bounds of ultrafiltration volume and rate were realized. The controller was evaluated in in silico and ex vivo bench experiments, and in a clinical proof-of-concept study in two maintenance dialysis patients. In all tests, the ultrafiltration controller performed as expected. In the in silico and ex vivo bench experiments, the controller showed robust reaction toward deliberate disruptive interventions (e.g. signal noise; extreme plasma refill rates). No adverse events were observed in the clinical study. The ultrafiltration controller can steer RBV trajectories toward desired RBV ranges while obeying to a set of constraints. Prospective studies in hemodialysis patients with diverse clinical characteristics are warranted to further explore the controllers impact on intradialytic hemodynamic stability, quality of life, and long-term outcomes.

Protocol of a pilot-scale, single-arm, observational study to assess the utility and acceptability of a wearable hydration monitor in haemodialysis patients

BackgroundFluid overload has a high prevalence in haemodialysis patients and is an important risk factor for excess mortality and hospitalisations. Despite the risks associated with chronic fluid overload, it is clinically difficult to assess and maintain fluid status adequately. Current methods of fluid status assessment are either imprecise or time intensive. In particular, to date, no method exists to accurately assess fluid status during the interdialytic interval.ObjectivesThis pilot study aimed to evaluate whether a prototype wearable hydration monitor can accurately and reproducibly detect fluid overload in the haemodialysis population when compared to haemodialysis and bioimpedance data.MethodsA prospective, open-label, single-arm observational trial of 20 patients commenced in January 2021 in a single haemodialysis centre in Ireland, with a wearable hydration monitor, the Sixty device. The Sixty device uses diffuse reflectance spectroscopy to measure fluid levels at the level of the subdermis and uses machine learning to develop an algorithm that can determine fluid status. The Sixty device was worn at every dialysis session and nocturnally over a three-week observational period. Haemodialysis parameters including interdialytic weight gain, ultrafiltration volume, blood pressure, and relative blood volume were collected from each session, and bioimpedance measurements using the Fresenius body composition monitor were performed on 4 occasions as a comparator. The primary objective of this trial was to determine the accuracy and reproducibility of the Sixty device compared to bioimpedance measurements.ConclusionIf the accuracy of the wearable hydration monitor is validated, further studies will be conducted to integrate the device output into a multi-parameter machine learning algorithm that can provide patients with actionable insights to manage fluid overload in the interdialytic period.Trial registrationwww.clinicaltrials.govNCT04623281. Registered November 10th, 2020.

High versus low ultrafiltration rates during experimental peritoneal dialysis in rats: Acute effects on plasma volume and systemic haemodynamics.

Intradialytic hypotension is a common complication of haemodialysis, but uncommon in peritoneal dialysis (PD). This may be due to lower ultrafiltration rates in PD compared to haemodialysis, allowing for sufficient refilling of the blood plasma compartment from the interstitial volume, but the underlying mechanisms are unknown. Here we assessed plasma volume and hemodynamic alterations during experimental PD with high versus low ultrafiltration rates. Experiments were conducted in two groups of healthy Sprague-Dawley rats: one group with a high ultrafiltration rate (N = 7) induced by 8.5% glucose and a low UF group (N = 6; 1.5% glucose), with an initial assessment of the extracellular fluid volume, followed by 30 min PD with plasma volume measurements at baseline, 5, 10, 15 and 30 min. Mean arterial pressure, central venous pressure and heart rate were continuously monitored during the experiment. No significant changes over time in plasma volume, mean arterial pressure or central venous pressure were detected during the course of the experiments, despite an ultrafiltration (UF) rate of 56 mL/h/kg in the high UF group. In the high UF group, a decrease in extracellular fluid volume of -7 mL (-10.7% (95% confidence interval: -13.8% to -7.6%)) was observed, in line with the average UF volume of 8.0 mL (standard deviation: 0.5 mL). Despite high UF rates, we found that plasma volumes were remarkably preserved in the present experiments, indicating effective refilling of the plasma compartment from interstitial tissues. Further studies should clarify which mechanisms preserve the plasma volume during high UF rates in PD.