Solute Clearance Research Articles

Targeting the brain's glymphatic pathway: a novel therapeutic approach for cerebral small vessel disease.

Cerebral small vessel disease encompasses a group of neurological disorders characterized by injury to small blood vessels, often leading to stroke and dementia. Due to its diverse etiologies and complex pathological mechanisms, preventing and treating cerebral small vessel vasculopathy is challenging. Recent studies have shown that the glymphatic system plays a crucial role in interstitial solute clearance and the maintenance of brain homeostasis. Increasing evidence also suggests that dysfunction in glymphatic clearance is a key factor in the progression of cerebral small vessel disease. This review begins with a comprehensive introduction to the structure, function, and driving factors of the glymphatic system, highlighting its essential role in brain waste clearance. Afterwards, cerebral small vessel disease was reviewed from the perspective of the glymphatic system, after which the mechanisms underlying their correlation were summarized. Glymphatic dysfunction may lead to the accumulation of metabolic waste in the brain, thereby exacerbating the pathological processes associated with cerebral small vessel disease. The review also discussed the direct evidence of glymphatic dysfunction in patients and animal models exhibiting two subtypes of cerebral small vessel disease: arteriolosclerosis-related cerebral small vessel disease and amyloid-related cerebral small vessel disease. Diffusion tensor image analysis along the perivascular space is an important non-invasive tool for assessing the clearance function of the glymphatic system. However, the effectiveness of its parameters needs to be enhanced. Among various nervous system diseases, including cerebral small vessel disease, glymphatic failure may be a common final pathway toward dementia. Overall, this review summarizes prevention and treatment strategies that target glymphatic drainage and will offer valuable insight for developing novel treatments for cerebral small vessel disease.

Mathematical model of solute transport in channels with variable geometry and permeable walls

This paper investigates solute transport dynamics within a steady, viscous, Newtonian fluid flow through channels of varying geometry (convergent–divergent boundaries) and permeable walls. The significant impact of osmotic pressure on solute concentration is particularly highlighted by modeling osmotic pressure as a cubic function of solute concentration. Approximate solutions to the Navier–Stokes equations and solute transport equations, along with the corresponding boundary conditions, have been derived. The effects of varying geometry and various emerging parameters on hydrostatic and osmotic pressures, solute concentration, and solute clearance are illustrated through graphs. Results indicate a linear decline in hydrostatic pressure and a nonlinear rise in osmotic pressure along the channel length, with divergent channels producing higher solute and wall concentrations than uniform or convergent channels. Increased ultrafiltration and absence of osmotic pressure yield greater wall concentrations. Solute clearance rates increase with the wall slope, transmittance coefficient, permeability, and ultrafiltration parameters, underscoring intricate parameter relationships within filtration. A dataset is used to visually present and analyze the influence of different physiological factors on solute concentration, with graphs corresponding to real physiological conditions. For channels with the uniform width, the findings closely align with previous results, demonstrating its applicability to solute exchange in glomerular capillaries as well as to other blood vessels or capillaries.

Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease

Divergent brain solute clearance in rat models of cerebral amyloid angiopathy and Alzheimer’s disease

Pulsed peritoneal dialysis in an experimental rat model: A first experience.

Peritoneal dialysis (PD) is commonly performed using either intermittent or tidal exchanges, whereas other exchange techniques such as continuous flow PD are little used. Previous research indicated that stirring the intra-peritoneal dialysate markedly increases small solute clearances. Here, we tested the hypothesis that stirring of the dialysate increases small solute clearances by using a novel exchange technique where the dialysate is pulsed back and forth during the treatment without addition of fresh fluid. PD was performed in anesthetized Sprague-Dawley rats with either no pulsations (20 mL fill volume), 2 mL (10%) pulses (21 mL fill volume), or 5 mL (25%) pulses (22.5 mL fill volume) utilizing a pulse flow rate of 5 mL/min. The higher fill volume for the pulsed treatments compensates for the fact that the average intra-peritoneal volume would otherwise be lower in pulsed treatments. Water and solute transport were closely monitored during the treatment. Net ultrafiltration decreased significantly during pulsed PD with the 25% pulse volume. The 60 min sodium dip was unaltered, whereas the fluid absorption rate was increased for the 25% group. Solute clearances did not significantly differ between groups, except for a slightly lower calcium clearance in the 25% group. Our data indicate that stirring the dialysate using pulsed exchanges does not provide any advantage compared to conventional exchange techniques. In contrast, pulsed treatments had slightly lower ultrafiltration and small solute transport. The present findings may have implications regarding the choice of tidal volume in automated PD, favoring smaller tidal volumes.

Loss of aquaporin-4 impairs cerebrospinal fluid solute clearance through cerebrospinal fluid drainage pathways

The aquaporin-4 (AQP4) water channel is essential in neurofluid dynamics. AQP4 loss impairs solute exchange between the cerebrospinal fluid (CSF) and interstitial fluid (ISF). However, whether AQP4 expression affects solute clearance from the CSF space to the extracranial space remains unclear. This study aimed to investigate this using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) following the intrathecal administration of gadolinium-based contrast agents (GBCAs) to AQP4 knockout (KO) rats. AQP4 KO rats showed reduced efflux of intrathecal GBCAs to the extracranial spaces through CSF drainage pathways and increased retention of intrathecal GBCAs in the CSF space compared with the controls. These results suggest that AQP4 loss impairs solute clearance from the CSF space to the extracranial spaces via the CSF drainage pathways. This study revealed a close relationship between AQP4 expression and CSF solute clearance, contributing to a better understanding of the function of AQP4 in neurofluid dynamics.

Glymphatic influx and clearance are perturbed in Huntington's disease.

The accumulation of mutant huntingtin protein aggregates in neurons is a pathological hallmark of Huntington's disease (HD). The glymphatic system, a brain-wide perivascular network, facilitates the exchange of interstitial fluid and cerebrospinal fluid (CSF), supporting interstitial solute clearance of brain wastes. In this study, we employed dynamic glucose-enhanced (DGE) MRI to measure d-glucose clearance from CSF as a tool to predict glymphatic function in a mouse model of HD. We found significantly diminished CSF clearance efficiency in HD mice before phenotypic onset. The impairment of CSF clearance efficiency worsened with disease progression. These DGE MRI findings in compromised glymphatic function were further verified with fluorescence-based imaging of CSF tracer influx, suggesting an impaired glymphatic function in premanifest HD. Moreover, expression of the astroglial water channel aquaporin-4 in the perivascular compartment, a key mediator of glymphatic function, was significantly diminished in both HD mouse brain and human HD brain. Our data, acquired using a clinically translatable MRI, indicate a perturbed glymphatic network in the HD brain. Further validation of these findings in clinical studies will provide insights into the potential of glymphatic clearance as a therapeutic target as well as an early biomarker in HD.

Relationship between fill volume and transport in peritoneal dialysis-from bench to bedside.

Larger fill volumes in peritoneal dialysis (PD) typically improve small solute clearance and water removal, and vice versa-but the relationship between intraperitoneal volume and the capacities for solute and water transport in PD has been little studied. Here, it is proposed that this relative relationship is described by a simple ratio (Volumenew/Volumeold)2/3 up to a critical break-point volume, beyond which further volume increase is less beneficial in terms of solute and water removal. To scrutinize this hypothesis, experiments were conducted in a rat model of PD alongside a retrospective analysis of data from a prior clinical study. Rats underwent PD with either three consecutive fills of 8 + 8 + 8 mL (n = 10) or 12 + 12 + 12 mL (n = 10), with 45-minute dwell time intervals. This approach yielded 60 estimations of water and solute transport, characterized by osmotic conductance to glucose and solute diffusion capacities, respectively. Comparative analysis of the predictive efficacy of the two models-the simple ratio versus the break-point model-was performed using Monte Carlo cross-validation. The break-point model emerged as a superior predictor for both water and solute transfer, demonstrating its capability to characterize both experimental data from rats and clinical data from patients. The present analysis indicates that relatively simple calculations can be used to approximate clinical effects on solute and water removal when prescribing a lower or higher fill volume to patients with PD.

Crucial role of Aquaporin-4 extended isoform in brain water Homeostasis and Amyloid-β clearance: implications for Edema and neurodegenerative diseases

The water channel aquaporin-4 (AQP4) is crucial for water balance in the mammalian brain. AQP4 has two main canonical isoforms, M23, which forms supramolecular structures called Orthogonal Arrays of Particles (OAP) and M1, which does not, along with two extended isoforms (M23ex and M1ex). This study examines these isoforms’ roles, particularly AQP4ex, which influences water channel activity and localization at the blood-brain barrier. Using mice lacking both AQP4ex isoforms (AQP4ex-KO) and lacking both AQP4M23 isoforms (OAP-null) mice, we explored brain water dynamics under osmotic stress induced by an acute water intoxication (AWI) model. AQP4ex-KO mice had lower basal brain water content than WT and OAP-null mice. During AWI, brain water content increased rapidly in WT and AQP4ex-KO mice, but was delayed in OAP-null mice. AQP4ex-KO mice had the highest water content increase at 20 min. Immunoblot analysis showed stable total AQP4 in WT mice initially, with increases at 30 min. AQP4ex and its phosphorylated form (p-AQP4ex) levels rose quickly, but the p-AQP4ex/AQP4ex ratio dropped at 20 min. AQP4ex-KO mice showed a compensatory rise in canonical AQP4 at 20 min post-AWI. These findings highlight the important role of AQP4ex in water content dynamics in both normal and pathological states. To evaluate brain waste clearance, amyloid-β (Aβ) removal was assessed using a fluorescent Aβ intra-parenchyma injection model. AQP4ex-KO mice demonstrated markedly impaired Aβ clearance, with extended diffusion distances and reduced fluorescence in cervical lymph nodes, indicating inefficient drainage from the brain parenchyma. Mechanistically, the polarization of AQP4 at astrocytic endfeet is essential for efficient clearance flow, aiding interstitial fluid movement into the CSF and lymphatic system. In AQP4ex-KO mice, disrupted polarization forces reliance on slower, passive diffusion for solute clearance, significantly reducing Aβ removal efficiency and altering extracellular space dynamics. Our results underscore the importance of AQP4ex in both brain water homeostasis and solute clearance, particularly Aβ. These findings highlight AQP4ex as a potential therapeutic target for enhancing waste clearance mechanisms in the brain, which could have significant implications for treating brain edema and neurodegenerative diseases like Alzheimer’s.

Effect of Intra-Dialytic Exercise Onhemodialysis Session Adequacy and Solutes Clearance and Rebound in Prevalent Hemodialysis Patients

Abstract Background Hemodialysis is an indispensable therapeutic intervention for patients with end-stage renal disease (ESRD). However, it has certain limitations in managing the reduction in physical functionality and cardiovascular fitness. On the other hand, intradialytic exercise has demonstrated potential in enhancing health-related quality of life (HRQOL) and cardiopulmonary fitness in patients with chronic kidney disease who are undergoing maintenance hemodialysis. Aim of the Work This study aimed to investigate the impact of intra-dialytic exercise on the efficiency of hemodialysis sessions, the clearance of various solutes, and solute rebound in patients with ESRD receiving regular hemodialysis. Patients and Methods The study included forty adult ESRD patients undergoing regular hemodialysis, divided into two groups: Group 1 (intra-dialytic exercise program) and Group 2 (no intra-dialytic exercise program). Clinical characteristics were matched between the groups to ensure unbiased findings. Results The intra-dialytic exercise group showed significantly lower blood urea nitrogen levels and higher urea reduction ratio (URR%) compared to the control group. Equilibrated Kt/V (eKt/V) values were also higher in the exercise group, suggesting more efficient dialysis treatment. In terms of minerals, the exercise group had reduced phosphorus levels and higher phosphorus reduction rate (Po4 RR%) compared to the control group. However, no significant difference was found in potassium levels between the groups. Conclusion The findings support previous research on the positive effects of intra-dialytic exercise on dialysis efficacy and electrolyte management. Intra-dialytic exercise may enhance waste product clearance and improve overall health outcomes in ESRD patients.

Lost dwell time and cycler alarms in inpatient automated peritoneal dialysis at a tertiary care hospital

Background and aims Dwell time is a critical component of automated peritoneal dialysis (APD) prescription, the stage at which transmembrane mass and fluid transfer occur. Loss of prescribed dwell time (LDT) can negatively influence the efficiency of APD. We investigated the incidence of LDT and related causes using APD in the acute care setting at a tertiary care center. Methods Retrospective analysis was conducted of all inpatients receiving APD treatments from 1 December 2021 to 1 June 2023. Patient demographics, comorbidities, laboratory, and treatment data were extracted from electronic medical records and a propriety database. Results N = 235 cycler treatments completed by 32 patients were included for analysis. The total LDT per treatment exceeding 30 minutes and 60 minutes occurred in 27% and 20% of all treatments. LDT of more than 10 minutes per each cycle exchange occurred in 26%. Session disruptions were caused by slow out-flow (55%), inadequate drain volumes (32%), patient line occlusions (20%), and priming errors (23%). The slow flow alarm requiring user intervention was reported to occur in about one-third of all treatments (31%). Conclusion There was significant LDT and inadequate drain volume seen in about one-quarter and one-third of all inpatient APD treatments respectively. This can impact solute clearance and ultrafiltration. Slow flow alarms were the most prevalent and the leading cause of LDT followed by inadequate drain volume. Future studies are required to investigate measures to reduce slow drain and improve drain volume in the hospital setting.

Genetically Modified Porcine Kidneys Have Sufficient Tissue Integrity for Use in Pig-to-Human Xenotransplantation.

We sought to determine if genetically modified porcine kidneys used for xenotransplantation had sufficient tissue integrity to support long-term function in a human recipient. Kidney transplantation remains the best available treatment for patients with end-stage kidney disease. However, a shortage of available donor human kidneys prevents many patients from achieving the benefits of transplantation. Xenotransplantation is a potential solution to this shortage. Recent pre-clinical human studies have demonstrated kidneys from genetically modified pig donors can be transplanted without hyperacute rejection and are capable of providing creatinine and other solute clearance. It is unknown whether the porcine kidneys would tolerate the relatively higher resting blood pressure in an adult human recipient compared with the pig donor or non-human primate (NHP) recipients used in translational studies. Furthermore, previous experience in NHPs raised concerns about the tissue integrity of the porcine ureter and post-xenotransplant growth of the porcine kidney. Kidneys recovered from porcine donors with 10 gene edits were transplanted into decedent brain-dead recipients who were not eligible for organ donation. Decedents underwent bilateral native nephrectomy before transplant and were followed for 3 to 7 days. Standard induction and maintenance immunosuppression was used as previously reported. Vital signs, including blood pressure, were recorded frequently. Kidney xenografts were assessed daily, serially biopsied, and were measured at implantation and study completion. Three decedents underwent successful xenotransplantation. Subcapsular hematomas developed, requiring incision of the xenograft capsules to prevent Page kidney. Blood pressures were maintained in a physiologic range for adult humans (median arterial pressures (MAP) 108.5mmHg (Interquartile Range (IQR): 97-114mmHg), 74mmHg (IQR: 71-78mmHg), and 95mmHg (IQR: 88-99mmHg, respectively) and no bleeding complications or aneurysm formation was observed. Serial biopsies were taken from the xenografts without apparent loss of tissue integrity despite the lack of a capsule. Ureteroneocystotomies remained intact without evidence of urine leak. Xenograft growth was observed, but plateaued, in 1 decedent with increased volume of the left and right xenografts by 25% and 26%, respectively, and in the context of human growth hormone levels consistently less <0.1ng/ml and insulin-like growth factor 1 levels ranging from 34-50ng/ml. The findings of this study suggest kidneys from 10-gene edited porcine donors have sufficient tissue integrity to tolerate xenotransplantation into a living human recipient. There was no evidence of anastomotic complications, and the xenografts tolerated needle biopsy without issue. Xenograft growth occurred but plateaued by the study end; further observation and investigation will be required to confirm this finding and elucidate underlying mechanisms.

Biological sex and BMI influence the longitudinal evolution of adolescent and young adult MRI-visible perivascular spaces.

An association recently emerged between magnetic resonance imaging (MRI)-visible perivascular spaces (MV-PVS) with intracerebral solute clearance and neuroinflammation, in adults. However, it is unknown how MV-PVS change throughout adolescence and what factors influence MV-PVS volume and morphology. This study assesses the temporal evolution of MV-PVS volume in adolescents and young adults, and secondarily evaluates the relationship between MV-PVS, age, sex, and body mass index (BMI). This analysis included a 783 participant cohort from the longitudinal multicenter National Consortium on Alcohol and Neurodevelopment in Adolescence study that involved up to 6 imaging visits spanning 5 years. Healthy adolescents aged 12-21 years at study entry with at least two MRI scans were included. The primary outcome was mean MV-PVS volume (mm 3 /white matter cm 3 ). On average, males had greater MV-PVS volume at all ages compared to females. A linear mixed-effect model for MV-PVS volume was performed. Mean BMI and increases in a person's BMI were associated with increases in MV-PVS volume over time. In females only, changes in BMI correlated with MV-PVS volume. One unit increase in BMI above a person's average BMI was associated with a 0.021 mm 3 /cm 3 increase in MV-PVS volume (p<0.001). This longitudinal study showed sex differences in MV-PVS features during adolescence and young adulthood. Importantly, we report that increases in BMI from a person's mean BMI are associated with increases in MV-PVS volume in females only. These findings suggest a potential link between MV-PVS, sex, and BMI that warrants future study.

Online Hemodiafiltration: A New Perspective for Patients With End-Stage Renal Disease.

Introduction Online hemodiafiltration (OL-HDF) is the most effective renal replacement therapy (RRT), which allows the enhanced removal of small and large uremic toxins by combining diffusion and convective transport of solutes. Although the goal of OL-HDF is to provide greater clearance of solutes with a preference for intermediate molecules responsible for many of the complications of chronic kidney disease (CKD), the studies reported to date and their meta-analyses are conflicting in nature and do not show a significant advantage of convective therapies on patient prognosis. Materials and methods At the Clinic of Nephrology and Dialysis, University Hospital "St. Marina", Varna, Bulgaria, 41 patients were monitored in a retrospective study for a two-year period, randomized into two groups, conducting OL-HDF after dilution and hemodialysis (HD) with the aim of studying the effect of convective therapies on the clinical outcome, the achieved quality of life, and the prognosis of the patient. Results The study found a significantly higher quality of life in patients undergoing OL-HDF with significantly higher values ​​of indicators of dialysis adequacy and nutritional status, better control of the anemic syndrome with the reduction of erythropoietin doses, significantly lower frequency of episodes of intradialytic hypotension with improved recovery, and 3.6-fold lower risk of death compared with conventional dialysis. Discussion Three major randomized controlled trials have compared survival outcomes in patients receiving HD or post-dilution OL-HDF, reporting conflicting results. Meta-analyses of the published studies have also been unable to provide a clear and definitive answer regarding the potential benefits of choosing one treatment over the other. Overall mortality, anemia, phosphate control, and small molecule clearance appear to be insufficiently influenced by the treatment method. On the other hand, cardiovascular mortality, hemodynamic stability, and clearance of middle and protein-bound molecules seem to be better in patients treated with OL-HDF. Conclusions Despite the conflicting data reported so far, OL-HDF is associated with better clinical outcome and prognosis for end-stage renal disease (ESRD) patient and undoubtedly warrants extensive future study with a view to improved quality of life in the growing dialysis population.

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.

Astrocyte regulation of extracellular space parameters across the sleep-wake cycle.

Multiple subfields of neuroscience research are beginning to incorporate astrocytes into current frameworks of understanding overall brain physiology, neuronal circuitry, and disease etiology that underlie sleep and sleep-related disorders. Astrocytes have emerged as a dynamic regulator of neuronal activity through control of extracellular space (ECS) volume and composition, both of which can vary dramatically during different levels of sleep and arousal. Astrocytes are also an attractive target of sleep research due to their prominent role in the glymphatic system, a method by which toxic metabolites generated during wakefulness are cleared away. In this review we assess the literature surrounding glial influences on fluctuations in ECS volume and composition across the sleep-wake cycle. We also examine mechanisms of astrocyte volume regulation in glymphatic solute clearance and their role in sleep and wake states. Overall, findings highlight the importance of astrocytes in sleep and sleep research.

Personalized peritoneal dialysis prescription—beyond clinical or analytical values

ABSTRACT Traditionally, dialysis adequacy has been assessed primarily by determining the clearance of a single small solute, urea. Nevertheless, it has become increasingly evident that numerous other factors play a crucial role in the overall well-being, outcomes and quality of life of dialysis patients. Consequently, in recent years, there has been a notable paradigm shift in guidelines and recommendations regarding dialysis adequacy. This shift represents a departure from a narrow focus only on the removal of specific toxins, embracing a more holistic, person-centered approach. This new perspective underscores the critical importance of improving the well-being of individuals undergoing dialysis while simultaneously minimizing the overall treatment burden. It is based on a double focus on both clinical outcomes and a comprehensive patient experience. To achieve this, a person-centered approach must be embraced when devising care strategies for each individual. This requires a close collaboration between the healthcare team and the patient, facilitating an in-depth understanding of the patient's unique goals, priorities and preferences while striving for the highest quality of care during treatment. The aim of this publication is to address the existing evidence on this all-encompassing approach to treatment care for patients undergoing peritoneal dialysis and provide a concise overview to promote a deeper understanding of this person-centered approach.

Enhanced transport of brain interstitial solutes mediated by stimulation of sensorimotor area in rats.

Solute transport in the brain is essential for maintaining cerebral homeostasis. Recent studies have shown that neuronal activity enhances the transport of cerebrospinal fluid solutes, but its impact on interstitial solute transport has not been established. In this study, we investigated whether neuronal activity affects the transport of interstitial solutes. Fluorescent Texas Red ovalbumin was injected intracortically into the unilateral sensorimotor area of the Sprague-Dawley rats. Regional neuronal activity around the injection site was elicited by transdermal electrical stimulation of a corresponding forelimb for 90 min ( n = 6). The control group of rats ( n = 6) did not receive any electrical stimulation. Subsequently, the spatial distributions of the tracer over the cortical surface and from the brain sections were imaged and compared between two groups. The ovalbumin fluorescence from the cervical lymph nodes was also compared between the groups to evaluate the effect of neuronal activity on solute clearance from the brain. Tracer distribution over the brain surface/sections revealed a significantly higher uptake of ovalbumin in the hemisphere ipsilateral to the injection among the stimulated animals compared to the unstimulated group. This difference, however, was not seen in the hemisphere contralateral to injection. A trace amount of ovalbumin in the lymph nodes was equivalent between the groups, which indicated a considerable time needed for interstitial solutes to be drained from the brain. The results suggest that neuronal activity enhances interstitial solute transport, calling for further examination of ultimate routes and mechanisms for brain solute clearance.

#1067 The impact of hemodialysis (HD) versus hemodiafiltration (HDF) on the effect of intradialytic exercise: a multicentre cohort study

Abstract Background and Aims Diminished physical function in HD patients is a critical issue, necessitating strategic approaches to enhance the efficacy of exercise therapy. The differential impacts of HD and HDF on solute clearance, albumin loss, uremic conditions, and malnutrition could influence the success of exercise interventions. Presently, empirical evidence for this is lacking. This investigation explores how HD and HDF modalities influence the efficacy of exercise therapy administered during dialysis sessions. Method This study encompassed intradialytic resistance exercises, involving 414 patients with end-stage renal disease across 10 centers. Participants were voluntarily enlisted in an exercise regimen during their dialysis sessions. The intradialytic regimen comprised stretching and four types of resistance exercises utilizing elastic tubes, conducted thrice weekly over six months. Parameters such as 10-meter walking speed, knee extensor muscle strength, serum albumin levels (Alb), normalized protein catabolic rate (nPCR), and Creatinine Generation Rate (%CGR) were assessed pre-and post-intervention. Statistical analysis included propensity score matching to adjust for baseline characteristics, segregating patients into HD and HDF cohorts. Changes in the aforementioned indicators before and after intervention (Δ) were calculated. Analytical methods included paired t-tests for within-group comparisons and independent t-tests for between-group comparisons of Δ values. A 5% risk threshold was established for statistical significance. Ethical clearance was obtained from the Seirei Christopher University Ethics Committee. Results A propensity score matching yielded 70 matched pairs. There were no significant differences in baseline subject characteristics after propensity score matching. Within-group analyses in the HD group revealed significant improvements in 10-meter walking speed (1.42 ± 0.41→1.60 ± 0.46 m/s, p = 0.000), knee extensor strength (44.3 ± 14.7→49.6 ± 13.8%, p = 0.000), and a reduction in Kt/V (1.69 ± 0.32→1.64 ± 0.32, p = 0.006) after six months. The HDF group significantly enhanced 10-meter walking speed (1.54 ± 0.40→1.72 ± 0.40, p = 0.000), knee extensor muscle strength (51.7 ± 17.1→57.4 ± 17.7%, p = 0.000), nPCR (0.88 ± 0.15→0.94 ± 0.18, p = 0.009), and %CGR (106.3 ± 23.2→112.9 ± 25.2, p = 0.002) (pre to post value, respectively). There are no significant differences in other variables between pre- and post-values in each group. Comparative analysis between groups demonstrated a significantly lower ΔAlb (HD 0.04 ± 0.24 HDF −0.05 ± 0.27, p = 0.045)and a higher 7, p =0(HD 1.47 ± 18.2 HDF 6.65 ± 17.2, p = 0.004)in the HDF group compared to the HD group. Conclusion The study demonstrated a notable HDF group improvement in %CGR, an indicator of muscle mass, despite a decrease in albumin levels. This suggests that albumin loss due to HDF minimally affects the augmentation of physical function. The findings suggest integrating exercise therapy with HDF may positively influence protein consumption and muscle mass enhancement.

#2879 Residual kidney function is more than urinary output alone in PD patients: insights derived from tubular functional Na MRI of the kidney

Abstract Background and Aims Maintenance of a cortico-medullary concentration gradient (CMG) is required for urine concentration and is one of most important tubular functions. We have previously demonstrated that the CMG can be quantified in both healthy controls and patients receiving HD, using 23NaMRI of the kidney. Peritoneal dialysis (PD) patients, in general, are considered to have better preservation of residual renal function (RKF), than comparative haemodialysis (HD) patients. We aimed to investigate if this was evident with respect to functional imaging of the CMG, to explore the concept that glomerular and tubular function may be dichotomized in patients with chronic kidney disease (CKD) requiring maintenance dialysis. Method We conducted an exploratory pilot study for 8 PD patients and 21 HD patients. Patients were instructed to fast from midnight before scanning. Urines samples were collected to measure osmolarity after fasting and a first MRI scan- performed to acquire baseline anatomical and sodium images. All MR imaging was carried out on a GE MR750 3T (GE Healthcare, WI) instrument. A custom-built two-loop (18cm in diameter) butterfly radiofrequency surface coil tuned for 23Na frequency (33.786 MHz) was used to acquire renal 23Na images. Results PD participants were 60 ± 10 years old, 50% male, mean body mass index (BMI) was 26.7 ± 4.6 kg/m2 and dialysis vintage was 20 ± 13 months, mean creatinine and urea clearance was 12 ± 7 mL/min/1.73 m2; HD participants were well matched, 60 ±18 years old, 52% men, BMI 27 ± 6 kg/m2 and dialysis vintage was 33 ± 25 months respectively. Urinary osmolarity was 284 ± 66 mosm/L and 239 ± 72, p = 0.1; mean medulla to cortex ratio was 1.2 ± 0.2 and 1.2 ± 0.1, p = 0.2 between PD and HD participants respectively. 7/8 PD participants were able to perform 24 hrs urine collection. Mean urine volume was substantial at 1525 ± 594 mL. We found no correlation between urine volume and corticomedullary gradient (Fig. 1A). Fig. 2C illustrates a 75 year old male, with medulla to cortex ratio at 1, urine volume 2100 mL, CLcrUr 18 mL/min/1.73 m2 and Fig. 1C showed a 55 years old patients, male, medulla to cortex ratio at 1.4, urine volume 2100 mL, CLcrUr 18 mL/min/1.73 m2. Conclusion These results underscore residual kidney function currently estimated by urine volume provides an incomplete assessment. Despite PD patients retaining higher degrees of RKF than HD patients, as assessed by urinary volume and small solute clearance, both patient groups have very similar degrees of directly imaged tubular function. The clinical importance of a focus on functional tubular mass to outcomes in dialysis patients is currently under further investigation.

#2784 Deep learning algorithm predicts individual ultrafiltration trajectories for patients on automated peritoneal dialysis 12 weeks ahead

Abstract Background and Aims Adequate small solute clearance and ultrafiltration (UF) are the main requirements for fluid and salt homeostasis on peritoneal dialysis (PD). New automated peritoneal dialysis (APD) systems that allow remote patient monitoring in terms of PD treatment analysis have the potential to improve clinical outcomes. UF on APD although dependent on PD prescription, i.e. fill volumes and glucose concentration, exhibits substantial intra- and interindividual variation, even day-by-day. As conventional statistical methods are not able to assess these complex non-linear relationships adequately, we aimed to build a deep learning algorithm to predict ultrafiltration trajectories of individual patients 12 weeks ahead. Method Data on daily UF and PD prescriptions (i.e., glucose concentration, fill volumes) was extracted from the APD cycler management software (PD Link, Baxter, IL, USA) and patient charts at the Medical University of Vienna, for a secondary analysis of this cohort. The Keras high-level API for TensorFlow in R software (R Core Team 2023) was used to create a Long Short-Term Memory (LSTM) recurrent neural network based on historic prescription and gcUF data of 26 weeks (after the first 90 days of APD) to predict individual UF trajectories for the following 12 weeks. Results APD machine readouts from a total of 123 patients, with a mean time on PD of 117 (±73) days, were retrieved. The final recurrent neural network consisted of four LSTM layers with 64 cells each, sigmoid activation. The final model was fit using 30 epochs, 49 steps per epoch, and recurrent dropout to avoid overfitting. A 40-40-20% data split was used to train, validate, and test the model adequately. This deep learning algorithm was able to predict individual UF values, for each day of the upcoming 12 weeks, with an accuracy of at mean 201ml. Upon visual inspection, predicted individual UF trajectories smoothly resemble the overall day-by-day trajectory of the patient but fail to account for extreme spikes in either direction. Conclusion In conclusion, historic daily APD cycler and prescription data in coalescence with respective daily measurements of membrane function (i.e., gcUF) can be used to predict individual daily ultrafiltration values and trajectories of APD patients 12 weeks ahead using a deep learning algorithm. Therefore, continuous collection of PD prescription data and UF measurements may be used to monitor peritoneal membrane function of patients on APD and alert clinical teams upon detection of relevant changes of UF trajectories already 12 weeks ahead to facilitate early intervention. In contrast to current “screening” methods on PD, i.e., Peritoneal Equilibrium Test, these methods could reduce treatment burden.