Solute Transfer Rate Research Articles

Recent advances in the understanding of the peritoneal membrane.

The efficiency of peritoneal dialysis (PD) as a life-sustaining replacement therapy for patients with kidney failure relies on the integrity and function of the peritoneal membrane. Here, we review the most recent advances in the understanding of the peritoneal membrane and its role in PD. A recent update of the ISPD guidelines proposed a revised definition of membrane dysfunction, emphasizing the importance of fluid balance in patients treated with PD and identified three main mechanisms leading to insufficient peritoneal ultrafiltration (UF). The Bio-PD study, the first genomewide association study in PD, demonstrated that 20% of the interindividual variability in the peritoneal solute transfer rate is genetically determined, and identified several loci of potential relevance for peritoneal transport. A candidate-gene approach identified and characterized a common and functional variant in the promoter of the AQP1 gene associated with water transport and clinical outcomes in PD. Innovative strategies to preserve the integrity of the peritoneal membrane and to enhance UF are also discussed, including the use of gliflozins; steady glucose concentration PD; modulation of GLUT proteins; and cytoprotective additives. A comprehensive understanding of the peritoneal membrane and of the mechanisms driving UF may help individualizing PD prescription and improving outcomes in patients treated with PD.

Can one long peritoneal dwell with icodextrin replace two short dwells with glucose?

Due to the slower dissipation of the osmotic gradient, icodextrin-based solutions, compared to glucose-based solutions, can improve water removal. We investigated scenarios where one icodextrin-based long dwell (Extraneal) replaced two glucose-based exchanges. The three-pore model with icodextrin hydrolysis was used for numerical simulations of a single exchange to investigate the impact of different peritoneal dialysis schedules on fluid and solute removal in patients with different peritoneal solute transfer rates (PSTRs). We evaluated water removal (ultrafiltration, UF), absorbed mass of glucose (AbsGluc) and carbohydrates (AbsCHO, for glucose and glucose polymers), ultrafiltration efficiency (UFE = UF/AbsCHO) per exchange, and specified dwell time, and removed solute mass for sodium (ReNa), urea (ReU), and creatinine (ReCr) for a single peritoneal exchange with 7.5% icodextrin (Extraneal®) and glucose-based solutions (1.36% and 2.27%) and various dwell durations in patients with fast and average PSTRs. Introducing 7.5% icodextrin for the long dwell to replace one of three or four glucose-based exchanges per day leads to increased fluid and solute removal and higher UF efficiency for studied transport groups. Replacing two glucose-based exchanges with one icodextrin exchange provides higher or similar water removal and higher daily sodium removal but slightly lower daily removal of urea and creatinine, irrespective of the transport type present in the case of reference prescription with three and four daily exchanges. One 7.5% icodextrin can replace two glucose solutions. Unlike glucose-based solutions, it resulted only in minor differences between PSTR groups in terms of water and solute removal with UFE remaining stable up to 16h.

Ultrafiltration Patterns during Automated Peritoneal Dialysis: Findings and Insights to Peritoneal Physiology.

With the growing use of automated peritoneal dialysis (APD), it is important to improve our knowledge of the clinical patterns and physiology of APD treatment sessions. The ultrafiltration (UF) achieved during each cycle of an APD treatment is assumed to be relatively linear if the delivered prescription is the same. We set out to determine if that is indeed the case. Single-center, cross-sectional study of prevalent PD patients. All adult APD patients (> 18 years of age), who had been on PD for >3 months, and >3 months on APD were included. Continuous ambulatory PD patients or those with peritonitis within 3 months of the consent date were excluded. Individual treatment data from 7 consecutive APD treatment sessions with consistent dialysate composition for each cycler exchange were collected for each subject. Thirty-nine subjects met the inclusion criteria and were enrolled. The probability of yielding a positive UF was 48.9% for cycle 1, rising to 90.5% by cycle 6. Adjusting for average dextrose concentration, dwell time, fill volume, solute transfer rate, and number of cycles, we observed that cycles 2 through 6 achieved progressively higher UF volumes than cycle 1 (p < 0.001). The first and last cycles demonstrated significantly different cycle UF volumes compared to a middle cycle (-230 ml and 277 ml, respectively, p < 0.001). We observed a consistent increase in UF volumes achieved per cycle over the course of an APD treatment session with numerous clinical and physiologic implications. This provides the foundation for future studies investigating peritoneal inter-cycle variations and membrane physiology.

Survival and its relationship with the type of peritoneal solute transfer rate, in patients with chronic kidney disease incident on peritoneal dialysis therapy in RTS Colombia between the years 2007–2017

IntroductionIn some studies, the peritoneal solute transfer rate (PSTR) through the peritoneal membrane has been related to an increased risk of mortality. It has been observed in the literature that those patients with rapid diffusion of solutes through the peritoneal membrane (high/fast transfer) and probably those with high average transfer characterized by the Peritoneal Equilibrium Test (PET) are associated with higher mortality compared to those patients who have a slow transfer rate. However, some authors have not documented this fact. In the present study, we want to evaluate the (etiological) relationship between the characteristics of peritoneal membrane transfer and mortality and survival of the technique in an incident population on peritoneal dialysis in RTS Colombia during the years 2007–2017 using a competing risk model. Materials and methodsA retrospective cohort study was carried out at RTS Colombia in the period between 2007 and 2017. In total, there were 8170 incident patients older than 18 years, who had a Peritoneal Equilibration Test (PET) between 28 and 180 days from the start of therapy. Demographic, clinical, and laboratory variables were evaluated. The (etiological) relationship between the type of peritoneal solute transfer rate at the start of therapy and overall mortality and technique survival were analyzed using a competing risk model (cause-specific proportional hazard model described by Royston-Lambert). ResultsPatients were classified into four categories based on the PET result: Slow/Low transfer (16.0%), low average (35.4%), high average (32.9%), and High/Fast transfer (15.7%). During follow-up, with a median of 730 days, 3025 (37.02%) patients died, 1079 (13.2%) were transferred to hemodialysis and 661 (8.1%) were transplanted. In the analysis of competing risks, adjusted for age, sex, presence of DM, HTA, body mass index, residual function, albumin, hemoglobin, phosphorus, and modality of PD at the start of therapy, we found cause-specific HR (HRce) for high/fast transfer was 1.13 (95% CI 0.98–1.30) p = 0.078, high average 1.08 (95% CI 0.96–1.22) p = 0.195, low average 1.09 (95% CI 0.96–1.22) p = 0.156 compared to the low/slow transfer rate. For technique survival, cause-specific HR for high/rapid transfer of 1.22 (95% CI 0.98–1.52) p = 0.66, high average HR was 1.10 (95% CI 0.91–1.33) p = 0.296, low average HR of 1.03 (95% CI 0.85–1.24) p = 0.733 compared with the low/slow transfer rate, adjusted for age, sex, DM, HTA, BMI, residual renal function, albumin, phosphorus, hemoglobin, and PD modality at start of therapy. Non-significant differences. ConclusionsWhen evaluating the etiological relationship between the type of peritoneal solute transfer rate and overall mortality and survival of the technique using a competing risk model, we found no etiological relationship between the characteristics of peritoneal membrane transfer according to the classification given by Twardowski assessed at the start of peritoneal dialysis therapy and overall mortality or technique survival in adjusted models. The analysis will then be made from the prognostic model with the purpose of predicting the risk of mortality and survival of the technique using the risk subdistribution model (Fine & Gray).

#2122 Dynamics of peritoneal transport and peritoneal dialysis outcomes

Abstract Background and Aims Volume overload is one of the most important factors associated with cardiovascular disease in peritoneal dialysis (PD) patients. On the other hand, the dynamics of peritoneal transport predicts important changes in the peritoneal membrane associated with local and systemic inflammation, which may be important for the progression of cardiovascular disease. The changes in free water transport (FWT) over time can characterize the development of peritoneal fibrosis. In a prospective study with retrospective historical control, the influence of the initial status and dynamics of peritoneal FWT on the outcomes of peritoneal dialysis, hard and surrogate cardiovascular outcomes was evaluated. Method According ISPD Recommendations (2021) the function of peritoneal membrane solute transfer was evaluated in classical PET in the exchange of 2 liters of 2.5% glucose solution with the calculation of the creatinine D/P4 ratio, which was used in the analysis as a continuous value (peritoneal solute transfer rate - PSTR), as well as categorized into high, medium-high, medium-low and low (H, HA, LA, L, respectively) levels of peritoneal transport. The mass transfer coefficient (MTAC) was also calculated. The ultrafiltration function of the membrane and its dynamics were evaluated by measuring the transport of water through small pores and free water through ultrapores, in double mini-PET (in two one-hour exchanges with solutions of 4.25% and 1.5% glucose). FWT is the calculated value; the primary measured value is the degree of reduction of sodium in the dialysis solution one hour after the start of the exchange (dipNa) formed as a result of electrolyte-free water transport through ultrapores (aquaporins), which dilutes dialysate. Results Table 1 shows the average values of peritoneal transport indicators at the beginning of follow-up and the annual changes calculated over the entire period of prospective follow-up for each patient. Major adverse cardiovascular events (Table 2) were recorded with a relatively low frequency, but significantly differed by incidence between the subgroups with high (H) and high-average (HA) peritoneal transport, on the one hand, and low-average (LA) and low(L), on the other: 0.626 ± 0.049 vs. 0.320 ± 0.042 events per year; p&amp;lt;0.001, (49% fewer events). Similarly, there was a significant difference in the MACE incidence between patients with slow and rapid decrease in free water transport (divided by the median of the rate of in free water transport decrease): 0.414 ± 0.044 vs. 0.510 ± 0.051 events per year; p &amp;lt; 0.001, (19% fewer events). The same calculations for nonfatal cardiovascular events showed a fewer incidence of 47.2% and 17.1%, respectively. Thus, patients with a high transport status (according to the PET test) and patients with a rapid decrease in water transport through aquaporins (indicating an increase in fibrotic changes in the peritoneal mesothelium), accompanied also by an increase in peritoneal permeability to solutes, including glucose, are at greater risk of progression of cardiovascular disease. Conclusion In addition to confirming the link between the initial status of peritoneal transport and the subsequent incidence of cardiovascular events, it would be interesting to confirm the influence of cardiovascular disease (as a proinflammatory condition and as a factor of volume overload, forcing the wider use of concentrated solutions which damage the peritoneum) on the progression of peritoneal fibrosis, but according to available materials it was not possible due to the limited number of patients in the study (especially – patients with repeated assessments of peritoneal transport after the cardiovascular events) and low frequency of peritoneal transport monitoring, on the one hand, and uncertainty in identifying the exact time of development of heart failure and the need for revascularization. Continued prospective observation would clarify these links.

Predicting solute transfer rate in patients initiating peritoneal dialysis

BackgroundWhile assessment of membrane characteristics is fundamental to peritoneal dialysis (PD) prescription in patients initiating therapy, peritoneal equilibration test has theoretical and practical drawbacks. We wished to determine whether an equation using simple clinical variables could predict fast (above population mean) peritoneal solute transfer rate without dialysate sampling.MethodsWe measured peritoneal solute transfer rate, as determined by peritoneal equilibration test using the 4-h dialysate to plasma creatinine ratio, in consecutive PD outpatients attending a single tertiary hospital for their first clinical follow-up within 3 months of dialysis initiation. An equation estimating peritoneal solute transfer rate based on readily available clinical variables was generated in a randomly selected modeling group and tested in a distinct validation group.ResultsWe included 712 patients, with 562 in the modeling group and 150 in the validation group. Mean age was 58.4 ± 15.9 with 431 (60.5%) men. Mean peritoneal solute transfer rate value was 0.73 ± 0.13. An equation based on gender, race, serum sodium and albumin yielded a receiving operator characteristics (ROC) area under the curve (AUC) to detect fast peritoneal solute transfer rate (> 0.73) of 0.74 (0.67–0.82). Estimated peritoneal solute transfer rate values based on percentiles 15th (> 0.66), 20th (> 0.68), 25th (> 0.69) and 30th (> 0.70) could rule out fast peritoneal solute transfer rate with negative predictive values of 100%, 93.5%, 84.2% and 80.0%, respectively.ConclusionsAn equation based on simple clinical variables allows ruling out fast transport in a significant proportion of patients initiating PD with a high degree of confidence without requiring dialysate sampling. This could prove useful in guiding dialysis prescription of PD patients in daily clinical practice, particularly in low-resource settings.Graphical abstract

Dapagliflozin in peritoneal dialysis patients: a pilot study evaluating peritoneal membrane function

BackgroundPatients taking SGLT-2 inhibitors may experience delayed peritoneal fibrosis, better ultrafiltration of water and toxins, and higher survival rates. We aimed to evaluate the possible effects of Dapagliflozin in changing the peritoneal solute transfer rate, reducing peritoneal glucose absorption, and, hence, increasing ultrafiltration.MethodologyA pilot pre-post interventional study was used to evaluate 20 patients on continuous ambulatory peritoneal dialysis (CAPD) enrolled in a one-month self-controlled study [Trial#: NCT04923295]. Inclusion criteria included being over 18, and having a Peritoneal Dialysis (PD) vintage of at least six months. All participants were classified as having high or average high transport status based on their Peritoneal Equilibrium Test with a D0/D4 > 0.39. and using at least two exchanges with 2.35% dextrose over the previous three months before enrollment.ResultsFollowing the treatment, 13 patients had an increase in median D4/D0 from 0.26 [0.17–0.38] to 0.31 [0.23–0.40], while seven patients had a decline from 0.28 [0.17–0.38] to 0.23 [0.14–0.33]. Additionally, nine patients had a decrease in median D/P from 0.88 [0.67–0.92] to 0.81 [0.54–0.85], while 11 patients had an increase from 0.70 [0.6–0.83] to 0.76 [0.63–0.91].ConclusionAccording to the findings of this study, Dapagliflozin usage in peritoneal dialysis patients did not result in a reduction in glucose absorption across the peritoneal membrane. Additionally, Dapagliflozin was also associated with a small increase in sodium dip, a decrease in peritoneal VEGF, and a decrease in systemic IL-6 levels all of which were not statistically significant. Further large-scale studies are required to corroborate these conclusions.

Magneto-double-diffusive natural convection and irreversibility analysis of a nanofluid flowing in an annular concentric space

In the present article, magneto-double-diffusive density driven convection accompanied by an entropy optimization analysis of Al2O3-water nanofluid filled in a horizontal coaxial annular space is numerically addressed. The double-diffusive natural nanofluid flow which is produced due to the maintaining of constant and different temperature and solute on the inner and outer cylinders is affected by a uniform vertical magnetic field. Dimensionless governed equations which are developed through law of conservation of mass, momentum, and energy are numerically solved via finite volume approach, and parametric control analysis is developed. By using Corcione empirical correlations considering the Brownian diffusion of 4% of Al2O3 nanoparticles in water, the thermal conductivity and viscosity of the mixture nanofluid are determined. Results are performed and interpreted in detail for wide range of relevant variables: Rayleigh (102 ≤ Ra ≤ 105), Hartmann (0 ≤ Ha ≤ 30), Lewis numbers (0 ≤ Le ≤ 10), and Buoyancy ratio (−4 ≤ N ≤ 4) to evaluate the double-diffusive convective nanofluid flow, heat and solute transfer rates as well as entropies produced in the system.

Tamoxifen exerts anti-peritoneal fibrosis effects by inhibiting H19-activated VEGFA transcription

BackgroundPeritoneal dialysis (PD) remains limited due to dialysis failure caused by peritoneal fibrosis. Tamoxifen (TAM), an inhibitor of estrogen receptor 1 (ESR1), has been reported to treat fibrosis, but the underlying mechanism remains unknown. In this study, we sought to explore whether tamoxifen played an anti-fibrotic role by affecting transcription factor ESR1.MethodsESR1 expression was detected in the human peritoneum. Mice were daily intraperitoneally injected with 4.25% glucose PD dialysate containing 40 mM methylglyoxal for 2 weeks to establish PD-induced peritoneal fibrosis. Tamoxifen was administrated by daily gavage, at the dose of 10 mg/kg. Chromatin immunoprecipitation (ChIP) and dual‐luciferase reporter assay were performed to validate ESR1 bound H19 promoter. Gain-of-function and loss-of-function experiments were performed to investigate the biological roles of H19 on the mesothelial-mesenchymal transition (MMT) of human peritoneal mesothelial cells (HPMCs). Intraperitoneal injection of nanomaterial-wrapped 2′-O-Me-modified small interfering RNA was applied to suppress H19 in the mouse peritoneum. RNA immunoprecipitation and RNA pull-down assays demonstrated binding between H19 and p300. Exfoliated peritoneal cells were obtained from peritoneal dialysis effluent to analyze the correlations between ESR1 (or H19) and peritoneal solute transfer rate (PSTR).ResultsESR1 was increased significantly in the peritoneum after long-term exposure to PD dialysate. Tamoxifen treatment ameliorated high glucose-induced MMT of HPMCs, improved ultrafiltration rate, and decreased PSTR of mouse peritoneum. Tamoxifen reduced the H19 level by decreasing the ESR1 transcription of H19. Depletion of H19 reversed the pro-fibrotic effect of high glucose while ectopic expression of H19 exacerbated fibrotic pathological changes. Intraperitoneal injection of nanomaterial-wrapped 2′-O-Me-modified siRNAs targeting H19 mitigated PD-related fibrosis in mice. RNA immunoprecipitation (RIP) and RNA pull-down results delineated that H19 activated VEGFA expression by binding p300 to the VEGFA promoter and inducing histone acetylation of the VEGFA promoter. ESR1 and H19 were promising targets to predict peritoneal function.ConclusionsHigh glucose-induced MMT of peritoneal mesothelial cells in peritoneal dialysis via activating ESR1. In peritoneal mesothelial cells, ESR1 transcribed the H19 and H19 binds to transcription cofactor p300 to activate the VEGFA. Targeting ESR1/H19/VEGFA pathway provided new hope for patients undergoing peritoneal dialysis.Graphic

Matrix metalloproteinase-10 deficiency has protective effects against peritoneal inflammation and fibrosis via transcription factor NFκΒ pathway inhibition

One of the most common causes of discontinued peritoneal dialysis is impaired peritoneal function. However, its molecular mechanisms remain unclear. Previously, by microarray analysis of mouse peritoneum, we showed that MMP (matrix metalloproteinase)-10 expression is significantly increased in mice with peritoneal fibrosis, but its function remains unknown. Chlorhexidine gluconate (CG) was intraperitoneally injected to wild-type and MMP-10 knockout mice to induce fibrosis to elucidate the role of MMP-10 on peritoneal injury. We also examined function of peritoneal macrophages and mesothelial cells obtained from wild-type and MMP-10 knockout mice, MMP-10-overexpressing macrophage-like RAW 264.7 cells and MeT-5A mesothelial cells, investigated MMP-10 expression on peritoneal biopsy specimens, and the association between serum proMMP-10 and peritoneal solute transfer rates determined by peritoneal equilibration test on patients. MMP-10 was expressed in cells positive for WT1, a mesothelial marker, and for MAC-2, a macrophage marker, in the thickened peritoneum of both mice and patients. Serum proMMP-10 levels were well correlated with peritoneal solute transfer rates. Peritoneal fibrosis, inflammation, and high peritoneal solute transfer rates induced by CG were all ameliorated by MMP-10 deletion, with reduction of CD31-positive vessels and VEGF-A-positive cells. Expression of inflammatory mediators and phosphorylation of NFκΒ subunit p65 at S536 were suppressed in both MMP-10 knockout macrophages and mesothelial cells in response to lipopolysaccharide stimulation. Overexpression of MMP-10 in RAW 264.7 and MeT-5A cells upregulated pro-inflammatory cytokines with phosphorylation of NFκΒ subunit p65. Thus, our results suggest that inflammatory responses induced by MMP-10 are mediated through the NFκΒ pathway, and that systemic deletion of MMP-10 ameliorates peritoneal inflammation and fibrosis caused by NFκΒ activation of peritoneal macrophages and mesothelial cells.

The centre-calculated cutoff value is better for identifying fast peritoneal solute transfer of patients on peritoneal dialysis than the traditional value: a retrospective cohort study.

The mean 4-h dialysate to plasma ratio of creatinine (4-h D/Pcr) is a vital cutoff value for recognizing the fast peritoneal solute transfer rate (PSTR) in patients on peritoneal dialysis (PD); however, it shows a noticeable centre effect. We aimed to investigate our centre-calculated cutoff value (CCV) of 4-h D/Pcr and compare it with the traditional cutoff value (TCV) (0.65). In this study, we enrolled incident PD patients at our centre from 2008 to 2019, and divided them into fast or non-fast PSTR groups according to baseline 4-h D/Pcr-based CCV or TCV. We compared the efficiency of the fast PSTR recognized by two cutoff values in predicting mortality, ultrafiltration (UF) insufficiency and technical survival. In total, 1905 patients were enrolled, with a mean 4-h D/Pcr of 0.71±0.11. Compared with TCV (0.65), CCV (0.71) showed superiority in predicting mortality of PD patients [hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.02-1.59 vs HR 1.24, 95% CI 0.97-1.59]. The odds ratio (OR) of the fast PSTR in centre classification was slightly higher than traditional classification in predicting UF insufficiency (OR 1.67, 95% CI 1.25-2.24 vs OR 1.60, 95% CI 1.15-2.22). Additionally, the restricted cubic splines 4-h D/Pcr has an S-shaped association with mortality and UF insufficiency, and the inflection points of 4-h D/Pcr were 0.71 (equal to CCV). The CCV of 4-h D/Pcr for identifying fast PSTR was 0.71. It was superior to TCV in predicting mortality and UF insufficiency.

Feasibility of [18F]fluoropivalate hybrid PET/MRI for imaging lower and higher grade glioma: a prospective first-in-patient pilot study

PurposeMRI and PET are used in neuro-oncology for the detection and characterisation of lesions for malignancy to target surgical biopsy and to plan surgical resections or stereotactic radiosurgery. The critical role of short-chain fatty acids (SCFAs) in brain tumour biology has come to the forefront. The non-metabolised SCFA radiotracer, [18F]fluoropivalate (FPIA), shows low background signal in most tissues except eliminating organs and has appropriate human dosimetry. Tumour uptake of the radiotracer is, however, unknown. We investigated the uptake characteristics of FPIA in this pilot PET/MRI study.MethodsTen adult glioma subjects were identified based on radiological features using standard-of-care MRI prior to any surgical intervention, with subsequent histopathological confirmation of glioma subtype and grade (lower-grade – LGG – and higher-grade – HGG – patients). FPIA was injected as an intravenous bolus injection (range 342–368 MBq), and dynamic PET and MRI data were acquired simultaneously over 66 min.ResultsAll patients tolerated the PET/MRI protocol. Three patients were reclassified following resection and histology. Tumour maximum standardised uptake value (SUVmax,60) increased in the order LGG (WHO grade 2) < HGG (WHO grade 3) < HGG (WHO grade 4). The net irreversible solute transfer, Ki, and influx rate constant, K1, were significantly higher in HGG (p < 0.05). Of the MRI variables studied, DCE-MRI-derived extravascular-and-extracellular volume fraction (ve) was high in tumours of WHO grade 4 compared with other grades (p < 0.05). SLC25A20 protein expression was higher in HGG compared with LGG.ConclusionTumoural FPIA PET uptake is higher in HGG compared to LGG. This study supports further investigation of FPIA PET/MRI for brain tumour imaging in a larger patient population.Clinical trial registrationClinicaltrials.gov, NCT04097535.

Supervivencia y su relación con el tipo de transferencia de solutos de membrana peritoneal, en pacientes con enfermedad renal crónica incidentes en terapia de diálisis peritoneal en RTS Colombia entre los años 2007-2017

IntroductionIn some studies, the peritoneal solute transfer rate (PSTR) through the peritoneal membrane has been related to an increased risk of mortality. It has been observed in the literature that those patients with rapid diffusion of solutes through the peritoneal membrane (high/fast transfer) and probably those with high average transfer characterized by the peritoneal equilibrium test (PET) are associated with higher mortality compared to those patients who have a slow transfer rate. However, some authors have not documented this fact. In the present study, we want to evaluate the (etiological) relationship between the characteristics of peritoneal membrane transfer and mortality and survival of the technique in an incident population on peritoneal dialysis in RTS Colombia during the years 2007 to 2017 using a competing risk model. Materials and methodsA retrospective cohort study was carried out at RTS Colombia in the period between 2007 and 2017. In total, there were 8170 incident patients older than 18 years, who had a PET between 28 and 180 days from the start of therapy. Demographic, clinical, and laboratory variables were evaluated. The (etiological) relationship between the type of peritoneal solute transfer rate at the start of therapy and overall mortality and technique survival were analyzed using a competing risk model (cause-specific proportional hazard model described by Royston-Lambert). ResultsPatients were classified into four categories based on the PET result: slow/low transfer (16.0%), low average (35.4%), high average (32.9%), and high/fast transfer (15.7%). During follow-up, with a median of 730 days, 3025 (37.02%) patients died, 1079 (13.2%) were transferred to hemodialysis and 661 (8.1%) were transplanted. In the analysis of competing risks, adjusted for age, sex, presence of DM, HTA, body mass index, residual function, albumin, hemoglobin, phosphorus, and modality of PD at the start of therapy, we found cause-specific HR (HRce) for high/fast transfer was 1.13 (95% CI 0.98–1.30) P = .078, high average 1.08 (95% CI 0.96–1.22) P = .195, low average 1.09 (95% CI 0.96–1.22) P = .156 compared to the low/slow transfer rate. For technique survival, cause-specific HR for high/rapid transfer of 1.22 (95% CI 0.98–1.52) P = .66, high average HR was 1.10 (95% CI 0.91–1.33) P = .296, low average HR of 1.03 (95% CI 0.85–1.24) P = .733 compared with the low/slow transfer rate, adjusted for age, sex, DM, HTA, BMI, residual renal function, albumin, phosphorus, hemoglobin, and PD modality at start of therapy. Non-significant differences. ConclusionsWhen evaluating the etiological relationship between the type of peritoneal solute transfer rate and overall mortality and survival of the technique using a competing risk model, we found no etiological relationship between the characteristics of peritoneal membrane transfer according to the classification given by Twardowski assessed at the start of peritoneal dialysis therapy and overall mortality or technique survival in adjusted models. The analysis will then be made from the prognostic model with the purpose of predicting the risk of mortality and survival of the technique using the risk subdistribution model (Fine & Gray).

#3478 THE EFFECT ON NET ULTRAFILTRATION WHEN TRANSFERRING PATIENTS FROM NOCTURNAL INTERMITTENT (NIPD) TO CONTINUOUS CYCLING PERITONEAL DIALYSIS (CCPD)

Abstract Background and Aims Peritoneal Dialysis (P.D.) Adequacy includes a variety of targets such as the sufficient uremic toxins removal (Κt/V), patients’ euvolemia, acid-base and electrolyte balance etc.. Based on incremental PD prescription NIPD is often a reasonable modality choice when there is adequate Residual Renal Function (RRF). Eventually due to RRF decrease patients need to increase their PD adequacy by adding a solution during the day i.e Icodextrin (CCPD). The aim of this study was to evaluate the alteration of Cyclers’ ultrafiltration(UF) as well as Total Ultrafiltration (sum of Cycler ultrafiltration and the UF of the initial drainage) when transferring patients from NIPD to CCPD Method This is a single center retroprospective study of 16 patients (m = 9,f = 7). These patients were transferred from NIPD to CCPD due to inadequate PD adequacy. The patients’ mean age was 53.4±19 years, their mean PD duration was 74.3±25.7 months and their mean Peritoneal Solute Transfer Rate (PSTR-D/Pcr) was 0.69±0.12. We evaluated small solute clearance targets (Kt/V – t:total,p:peritoneal,r:renal), RRF (eGFR, Vurine), Cycler’ ultrafiltration, the UF of the initial drainage and the sum of them (Total UF) on three consecutive days before the initiation of CCPD and three consecutive days after the initiation. The patients’ cycler treatment program remain constant and all of them received an initial day volume of 1000 ml with Icodextrin. Results We compared the alterations with Paired t-Test (normal distripution) We found a statistically significant improvement of the peritoneal fraction of Kt/V when applying CCPD (p = 0.01), on the other hand we found a statistically significant decrease from Cycler's UF (p&amp;lt;0.05) as well as from Total UF (p&amp;lt;0.05) without any statistically significant increase in urine's volume. Additionally, from the regression analysis there was statistically significant correlation between PSTR and ΔUF(UFNIPD-UFCCPDtotal) showing that the faster the transporter the greater the ultrafiltration loss (p = 0.035, R = 0.58). Conclusion Transferring patients with adequacy problems from NIPD to CCPD improves small solute clearances but in some cases the risk for total ultrafiltration decrease is important and may lead to overhydration. It is necessary to contact perspective studies with hydration status evaluation ie Bioimpedance Spectroscopy.

Gene polymorphisms of VEGF and KDR are associated with initial fast peritoneal solute transfer rate in peritoneal dialysis

BackgroundPeritoneal dialysis (PD) is an effective and successful renal replacement therapy. The baseline peritoneal solute transfer rate (PSTR) is related to local membrane inflammation and may be partially genetically determined. Herein, we focused on vascular endothelial growth factor (VEGF) and its receptor, kinase insert domain containing receptor (KDR).MethodsThis study recruited 200 PD patients from Renji Hospital in Shanghai, China. We analysed the association between the polymorphisms of VEGF and KDR and the 4-hour dialysate-to-plasma ratio for creatinine (4 h D/P Cr), which was measured between one and three months after initiating PD.ResultsThe CC genotype in VEGF rs3025039 and the AA genotype in KDR rs2071559 were both positively associated with a fast baseline PSTR (VEGF rs3025039 CC vs. TT + TC: 0.65 ± 0.12 vs. 0.61 ± 0.11; P = 0.029; KDR rs2071559 AA vs. GA + GG: 0.65 ± 0.12 vs. 0.62 ± 0.12; P = 0.039).ConclusionBaseline PSTR was partly determined by VEGF and KDR gene polymorphisms.

Peritoneal equilibration testing: Your questions answered.

The peritoneal equilibration test (PET), first described in 1987, is a semiquantitative assessment of peritoneal transfer characteristics in patients undergoing peritoneal dialysis. It is typically performed as a 4-h exchange using 2.27/2.5% dextrose dialysate with serial measurements of blood and dialysate creatinine, urea, and glucose concentrations. The percentage absorption of glucose and D/P creatinine ratio are used to determine peritoneal solute transfer rates. It is used to both help guide peritoneal dialysis prescriptions and to prognosticate. There are several derivative tests which have been described in the literature. In this review, we describe the original PET, the various iterations of the PET, the information gleaned, and the use in the setting of poor solute clearance and in the diagnosis of membrane dysfunction, and limitations of the PET.

Predictors of serum vancomycin levels in peritoneal dialysis-associated peritonitis.

Intraperitoneal (IP) vancomycin is often first-line empiric therapy for peritoneal dialysis (PD) peritonitis; however, whether dosing should be adjusted for patient-specific characteristics remains unclear. We sought to identify factors associated with the day 3 vancomycin serum level in patients receiving vancomycin for PD peritonitis. Retrospective single-centre adult cohort of 58 patients with PD peritonitis treated with IP vancomycin between January 2016 and May 2022. Linear regression was used to examine the association between day 3 vancomycin level and candidate predictors including age, sex, weight, glomerular filtration rate (GFR), urea and creatinine clearance (total, residual, dialysate), PD modality, peritoneal solute transfer rate and initial vancomycin dose. Logistic regression was used to evaluate the likelihood of achieving a level (≥15 mg/L) associated with these predictor variables. A 2-g loading dose was given in 51 cases, and 38 patients (66%) had a therapeutic day 3 level. Each 5 mg/kg increase in initial vancomycin dose was associated with a 1.38 mg/L (95% confidence interval 0.52, 2.23) increase in day 3 level. Each 1 mL/min increase in GFR was associated with a 0.29 mg/L decrease (95% confidence interval 0.05, 0.52) in day 3 level. The likelihood of achieving a therapeutic level was approximately four times higher with an initial dose of ≥25 mg/kg compared to <25 mg/kg (odds ratio 3.75, 95% confidence interval 1.05, 13.46). Following an average 2-g vancomycin loading dose for suspected PD peritonitis, one-third of patients were subtherapeutic on day 3. GFR and weight-based dosing were independently associated with day 3 vancomycin level, and their consideration could improve the likelihood of achieving an early therapeutic level.

Peritoneal Small Solute Transfer Rate (PSTR) vs. Clinical Outcome in Peritoneal Dialysis Patients: Assessment by Restricted Mean Survival Times (RMST)

Peritoneal Small Solute Transfer Rate (PSTR) vs. Clinical Outcome in Peritoneal Dialysis Patients: Assessment by Restricted Mean Survival Times (RMST)

Relative Contributions of Pseudohypoxia and Inflammation to Peritoneal Alterations with Long-Term Peritoneal Dialysis Patients.

Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.

International Icodextrin Use and Association with Peritoneal Membrane Function, Fluid Removal, Patient and Technique Survival.

Icodextrin has been shown in randomized controlled trials to benefit fluid management in peritoneal dialysis (PD). We describe international icodextrin prescription practices and their relationship to clinical outcomes. We analyzed data from the prospective, international PDOPPS, from Australia/New Zealand, Canada, Japan, the United Kingdom, and the United States. Membrane function and 24-hour ultrafiltration according to icodextrin and glucose prescription was determined at baseline. Using an instrumental variable approach, Cox regression, stratified by country, was used to determine any association of icodextrin use to death and permanent transfer to hemodialysis (HDT), adjusted for demographics, comorbidities, serum albumin, urine volume, transplant waitlist status, PD modality, center size, and study phase. Icodextrin was prescribed in 1986 (35%) of 5617 patients, >43% of patients in all countries, except in the United States, where it was only used in 17% and associated with a far greater use of hypertonic glucose. Patients on icodextrin had more coronary artery disease and diabetes, longer dialysis vintage, lower residual kidney function, faster peritoneal solute transfer rates, and lower ultrafiltration capacity. Prescriptions with or without icodextrin achieved equivalent ultrafiltration (median 750 ml/d [interquartile range 300-1345 ml/d] versus 765 ml/d [251-1345 ml/d]). Icodextrin use was not associated with mortality (HR=1.03; 95% CI, 0.72 to 1.48) or HDT (HR 1.2; 95% CI, 0.92 to 1.57). There are large national and center differences in icodextrin prescription, with the United States using significantly less. Icodextrin was associated with hypertonic glucose avoidance but equivalent ultrafiltration, which may affect any potential survival advantage or HDT.