The osmo-metabolic approach: a novel and tantalizing glucose-sparing strategy in peritoneal dialysis.
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ABSTRACT:
SUBMITTER: Bonomini M
PROVIDER: S-EPMC8036224 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Glucose-containing peritoneal dialysis solutions may exacerbate metabolic abnormalities and increase cardiovascular risk in diabetic patients. Here, we examined whether a low-glucose regimen improves metabolic control in diabetic patients undergoing peritoneal dialysis. Eligible patients were randomly assigned in a 1:1 manner to the control group (dextrose solutions only) or to the low-glucose intervention group (IMPENDIA trial: combination of dextrose-based solution, icodextrin and amino acids; EDEN trial: a different dextrose-based solution, icodextrin and amino acids) and followed for 6 months. Combining both studies, 251 patients were allocated to control (n=127) or intervention (n=124) across 11 countries. The primary endpoint was change in glycated hemoglobin from baseline. Mean glycated hemoglobin at baseline was similar in both groups. In the intention-to-treat population, the mean glycated hemoglobin profile improved in the intervention group but remained unchanged in the control group (0.5% difference between groups; 95% confidence interval, 0.1% to 0.8%; P=0.006). Serum triglyceride, very-low-density lipoprotein, and apolipoprotein B levels also improved in the intervention group. Deaths and serious adverse events, including several related to extracellular fluid volume expansion, increased in the intervention group, however. These data suggest that a low-glucose dialysis regimen improves metabolic indices in diabetic patients receiving peritoneal dialysis but may be associated with an increased risk of extracellular fluid volume expansion. Thus, use of glucose-sparing regimens in peritoneal dialysis patients should be accompanied by close monitoring of fluid volume status.
| S-EPMC3810077 | biostudies-literature
Project description:The main reason why peritoneal dialysis (PD) still has limited use in the management of patients with end-stage renal disease (ESRD) lies in the fact that the currently used glucose-based PD solutions are not completely biocompatible and determine, over time, the degeneration of the peritoneal membrane (PM) and consequent loss of ultrafiltration (UF). Here we evaluated the biocompatibility of a novel formulation of dialytic solutions, in which a substantial amount of glucose is replaced by two osmometabolic agents, xylitol and l-carnitine. The effect of this novel formulation on cell viability, the integrity of the mesothelial barrier and secretion of pro-inflammatory cytokines was evaluated on human mesothelial cells grown on cell culture inserts and exposed to the PD solution only at the apical side, mimicking the condition of a PD dwell. The results were compared to those obtained after exposure to a panel of dialytic solutions commonly used in clinical practice. We report here compelling evidence that this novel formulation shows better performance in terms of higher cell viability, better preservation of the integrity of the mesothelial layer and reduced release of pro-inflammatory cytokines. This new formulation could represent a step forward towards obtaining PD solutions with high biocompatibility.
| S-EPMC7795315 | biostudies-literature
Project description:IntroductionThe osmotic conductance to glucose (OCG) is a crucial determinant of ultrafiltration (UF) in peritoneal dialysis (PD) patients and can be used to monitor membrane integrity in patients on long-term PD. It has been proposed that OCG can be assessed based on drained volumes in 2 consecutive 1-hour glucose dwells, usually 1.5% and 4.25% glucose, in a so-called double mini-peritoneal equilibration test (dm-PET). However, recent data indicated that the dm-PET provides a poor estimate of OCG unless the residual volume (RV) is taken into account. We introduce an easy, robust, and accurate method to measure OCG and compare it with conventional methods.MethodsIn a prospective cohort of 21 PD patients, a modified version of the dm-PET was performed, along with the determination of RV before, between, and after dwells. Based on computer simulations derived from the 3-pore model (TPM) for membrane permeability, we developed and validated a novel single-dwell method to estimate OCG. We next validated the equation in an independent cohort consisting of 32 PD patients.ResultsSingle-dwell OCG correlated more closely with actual UF (r = 0.94 vs. r = 0.07 for conventional dm-PET), sodium sieving, and free water transport (FWT) compared with other methods. These findings were replicated in the validation cohort in which OCG calculated using the single-dwell method closely correlated with parameters of osmotic water transport, even when RV was not taken into account, using only drained volumes.ConclusionWe propose a novel, easy, and robust single-dwell method to determine OCG in individual patients and to monitor membrane integrity over time on PD.
| S-EPMC7610002 | biostudies-literature
Project description:BackgroundThe aim of this study was to evaluate the impact of peritoneal dialysis (PD) strategy on technique and patient survival.MethodsThis was a retrospective, single-center study conducted on consecutive patients with chronic kidney disease who underwent PD between January 2009 and December 2019. The study sample was stratified into four different groups according to PD technique [automated (APD) or manual (CAPD)] and icodextrin use (yes versus no). The primary endpoints were survival of both technique and patient.ResultsA total of 531 patients were included in the analysis. Mean ± standard deviation age was 60.6 ± 14.6 years, 68.4% (363) were men and 34.8% (185) had diabetes. The median technique survival time was 19 (15) months. A total of 185 (34.8%), 96 (18.1%), 99 (18.7%) and 151 (28.4%) patients were included in the CAPD/No-Icodextrin, CAPD/Icodextrin, APD/No-Icodextrin and APD/Icodextrin study groups, respectively. Throughout the study, 180 (33.9%) patients underwent renal transplant, 71 (13.4%) were changed to hemodialysis and 151 (28.4%) died. Age [hazard ratio (HR) 0.975, 95% confidence interval (CI) 0.960-0.990, P = .001] and incidence of early peritoneal infection (HR 2.440, 95% CI 1.453-4.098, P = .001) were associated with technique survival, while age (HR 1.029, 95% CI 1.013-1.045, P < .001), Charlson Index (HR 1.192, 95% CI 1.097-1.295, P < 0.001), use of icodextrin (HR 0.421, 95% CI 0.247-0.710, P < .001) and APD/Icodextrin (HR 0.499, 95% CI 0.322-0.803, P = .005) were associated with patient survival.ConclusionsIcodextrin use and APD/Icodextrin had a positive impact on patient survival, while older age and higher Charlson Index had a negative one. Age and incidence of early peritoneal infection significantly impacted on technique survival.
| S-EPMC10689157 | biostudies-literature
Project description:Background and objectivesWhile peritoneal dialysis with icodextrin is commonly used in patients with poor peritoneal membrane characteristics, the data on the usefulness of this solution in patients with lower transport characteristics are limited. The study was designed to compare icodextrin to glucose in Chinese prevalent peritoneal dialysis patients of different peritoneal transport characteristics (PET) categories.Design, setting, participants, & measurementsThis was a randomized, double-blind, perspective control study. Stable prevalent continuous ambulatory peritoneal dialysis (CAPD) patients were randomized to either 7.5% icodextrin (ICO) or 2.5% glucose (GLU) solution for 4 wk. Peritoneal membrane function was measured to define PET category in baseline. Creatinine clearance (Ccr), urea nitrogen clearance (C(BUN)), ultrafiltration (UF) during the long night dwell, dialysate, and metabolic biomarkers were measured at baseline, 2, and 4 wk. UF, Ccr, and C(BUN) were compared among different PET categories.ResultsA total of 201 CAPD patients were enrolled in the study. There were no baseline differences between the groups. Following 2 and 4 wk of therapy, Ccr, C(BUN,) and UF were all significantly higher in the ICO versus the GLU group. Additionally, switching to ICO resulted in a significant increase in UF in high, high-average, and low-average transporters as compared with baseline. The extent of increased UF was more obvious in higher transporters. Blood cholesterol level in the ICO group decreased significantly than that in the GLU group.ConclusionCompared with glucose-based solution, 7.5% icodextrin significantly improved UF and small solute clearance, even in patients with low-average peritoneal transport.
| S-EPMC2774964 | biostudies-literature
Project description:Longitudinal surveillance of peritoneal membrane function is crucial in defining patients with a risk of ultrafiltration failure. Long PD is associated with increased low molecular weight solute transport and decreased ultrafiltration and free water transport. Classic PET test only provides information about low molecular solute transport, and the vast majority of longitudinal studies are based on this test and include patients using conventional dialysates. Our aim was to prospectively analyze longitudinal data on peritoneal function in patients on biocompatible solutions using a novel test. Membrane function data were collected based on uni-PET (a combination of modified and mini PET). A total of 85 patients (age 61.1 ± 15.1 years) with at least one test/year were included. The median follow up was 36 months (21.3, 67.2). A total of 219 PETs were performed. One-way repeated measures ANOVA showed that there were no statistically significant differences over time in ultrafiltration, free water transport, ultrafiltration through small pores, sodium removal, D/D0 and D/PCre in repeated PET-tests. Twenty-three tests revealed ultrafiltration failure in 16 (18.8%) patients. Those patients were longer on PD, had higher D/P creatinine ratios, lower ultrafiltration at one hour with lower free water transport and higher urine volume at baseline. Multivariate analysis revealed that the variation of ultrafiltration over repeated PET-tests independently correlated only with D/Pcreatinine, free water transport and ultrafiltration through small pores. Uni-PET is a combination of two tests that provides more information on the function of the membrane compared with PET. Our study on a PD cohort using only biocompatible solutions revealed that function membrane parameters remained stable over a long time. Ultrafiltration failure was correlated with increased D/P creatinine and decreased free water transport and ultrafiltration through small pores.
| S-EPMC8396924 | biostudies-literature
Project description:Heat sterilization of peritoneal dialysis fluids (PDFs) leads to the formation of glucose degradation products (GDPs), which impair long-term peritoneal dialysis. The current study investigated the effects of metal ions, which occur as trace impurities in the fluids, on the formation of six major α-dicarbonyl GDPs, namely glucosone, glyoxal, methylglyoxal, 3-deoxyglucosone, 3-deoxygalactosone, and 3,4-dideoxyglucosone-3-ene. The chelation of metal ions by 2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid (DTPA) during sterilization significantly decreased the total GDP content (585 μM vs. 672 μM), mainly due to the decrease of the glucose-oxidation products glucosone (14 μM vs. 61 μM) and glyoxal (3 μM vs. 11 μM), but also of methylglyoxal (14 μM vs. 31 μM). The glucose-dehydration products 3-deoxyglucosone, 3-deoxygalactosone, and 3,4-dideoxyglucosone-3-ene were not significantly affected by chelation of metal ions. Additionally, PDFs were spiked with eleven different metal ions, which were detected as traces in commercial PDFs, to investigate their influence on GDP formation during heat sterilization. Iron(II), manganese(II), and chromium(III) had the highest impact increasing the formation of glucosone (1.2-1.5 fold increase) and glyoxal (1.3-1.5 fold increase). Nickel(II) and vanadium(III) further promoted the formation of glyoxal (1.3 fold increase). The increase of the pH value of the PDFs from pH 5.5 to a physiological pH of 7.5 resulted in a decreased formation of total GDPs (672 μM vs 637 μM). These results indicate that the adjustment of metal ions and the pH value may be a strategy to further decrease the content of GDPs in PDFs.
| S-EPMC8116238 | biostudies-literature
Project description:UNLABELLED:? BACKGROUND:A low protein diet supplemented with ketoacids has been shown to improve the metabolic profile, including insulin resistance, in patients with chronic kidney disease (CKD), but whether ketoacids alone exert similar effects is unknown. In this prospective randomized controlled trial, we aimed to evaluate the effects of ketoacid supplementation on insulin resistance, systemic inflammation, oxidative stress and endothelial dysfunction among 100 CKD patients undergoing peritoneal dialysis (PD). ? METHODS:Patients from one Chinese PD center were randomly assigned to take ketoacids (12 tablets per day) (n = 50) versus a control group (n = 50) for 6 months in an open-label parallelarm design. Daily protein intake of 0.8 - 1.2 g/kg/d and daily energy intake of 25 - 35 kcal/kg/d was prescribed to both groups. Insulin resistance was evaluated using homeostatic model assessment (HOMA-IR) index as the primary outcome. We assessed systemic inflammation using high-sensitive C-reactive protein (hs-CRP) and interleukin-6 (IL-6), oxidative stress using plasma oxidized low density lipoprotein (oxLDL), adipokines using leptin and adiponectin and endothelial dysfunction using serum soluble intercellular adhesion molecule-1 (sICAM) and soluble vascular adhesion molecule-1 (sVCAM) as secondary outcomes. ? RESULTS:There were no significant differences in baseline characteristics between the 2 groups except a slightly higher age in patients assigned to the intervention. A total of 89% of participants completed the 6-month intervention. There was no significant difference in the change of HOMA-IR values from baseline between groups after adjusting for baseline age, gender, body mass index and HOMA-IR. For secondary outcomes, hs-CRP varied significantly between groups (p = 0.02), increasing over time for the control group while remaining stable for the ketoacid group. Similarly, the leptin/adiponectin ratio (LAR) differed between groups (p < 0.001), remaining stable in the ketoacid group but increasing in the control group. ? CONCLUSION:Ketoacid therapy administered for 6 months had no effect on HOMA-IR but resulted in improvements in hs-CRP and LAR, suggesting metabolic benefit. Future studies are needed to confirm these results and any potential benefit in vascular health of PD patients.
| S-EPMC4690629 | biostudies-literature
Project description:Unlabelled?BackgroundPeritoneal dialysis (PD) has limited power for liquid extraction (ultrafiltration), so fluid overload remains a major cause of treatment failure. ?MethodsWe present steady concentration peritonal dialysis (SCPD), which increases ultrafiltration of PD exchanges by maintaining a constant peritoneal glucose concentration. This is achieved by infusing 50% glucose solution at a constant rate (typically 40 mL/h) during the 4-hour dwell of a 2-L 1.36% glucose exchange. We treated 21 fluid overload episodes on 6 PD patients with high or average-high peritoneal transport characteristics who refused hemodialysis as an alternative. Each treatment consisted of a single session with 1 to 4 SCPD exchanges (as needed). ?ResultsUltrafiltration averaged 653 ± 363 mL/4 h - twice the ultrafiltration of the peritoneal equilibration test (PET) (300 ± 251 mL/4 h, p < 0.001) and 6-fold the daily ultrafiltration (100 ± 123 mL/4 h, p < 0.001). Serum and peritoneal glucose stability and dialysis efficacy were excellent (glycemia 126 ± 25 mg/dL, peritoneal glucose 1,830 ± 365 mg/dL, D/P creatinine 0.77 ± 0.08). The treatment reversed all episodes of fluid overload, avoiding transfer to hemodialysis. Ultrafiltration was proportional to fluid overload (p < 0.01) and inversely proportional to final peritoneal glucose concentration (p < 0.05). ?ConclusionThis preliminary clinical experience confirms the potential of SCPD to safely and effectively increase ultrafiltration of PD exchanges. It also shows peritoneal transport in a new dynamic context, enhancing the influence of factors unrelated to the osmotic gradient.
| S-EPMC5033632 | biostudies-literature
Project description:BackgroundIrisin is a recently discovered myokine thought to be involved in multiple metabolism abnormalities in most dialysis patients. However, the myokine has not been thoroughly studied in peritoneal dialysis. This study aimed to evaluate serum irisin levels and establish their relation to dialysis adequacy, insulin resistance, and bone metabolism status in patients on peritoneal dialysis.MethodsA total of 59 nondiabetic prevalent peritoneal dialysis patients and 52 age- and sex-matched healthy controls were enrolled in this cross-sectional study. Serum irisin concentration was assessed by enzyme-linked immunosorbent assay. The correlations between serum irisin and dialysis adequacy, clinical, and metabolic variables were investigated.ResultsSerum irisin levels were lower in nondiabetic peritoneal dialysis patients (17.02ng/ml) compared with healthy controls (22.17ng/ml, P<0.001). Multivariate regression analysis revealed that fasting glucose levels were correlated inversely with serum irisin levels in peritoneal dialysis patients. Serum irisin levels were associated with neither insulin resistance nor bone metabolism in our patients. Serum irisin levels were positively associated with peritoneal Kt/Vurea (β = 4.933, 95% confidence interval [CI] = 0.536-9.331, P = 0.029) and peritoneal CCr (β = 0.259, 95% CI = 0.053-0.465, P = 0.015) among peritoneal dialysis patients.ConclusionsThe study demonstrated that non-diabetic peritoneal dialysis patients have lower serum irisin levels, and the levels were correlated with peritoneal dialysis adequacy, indicating adequate dialysis may improve irisin secretion. Additional studies are needed to provide a confirmation.
| S-EPMC5406024 | biostudies-literature