Dapagliflozin in peritoneal dialysis patients: a pilot study evaluating peritoneal membrane function
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SUBMITTER: Hamdan Z
PROVIDER: S-EPMC10811926 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:IntroductionPreservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality.MethodsWe conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined.ResultsOne hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (-28.0 ml/min per year; 95% CI: -60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (-291 ml/min per year; 95% CI: -550 to -32) while this was absent in biocompatible treatment.ConclusionDespite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions.
| S-EPMC7710881 | biostudies-literature
Project description:IntroductionVarious studies have reported the importance of complement regulators in preventing mesothelial damage during peritoneal dialysis (PD). Its assessment, however, is limited in clinical practice due to the lack of easy access to the peritoneal membrane. Recently, a soluble form of the complement regulatory protein CD59 (sCD59) has been described. We therefore aimed to investigate the role of sCD59 in PD.MethodsPlasma sCD59 was measured in 48 PD patients, 41 hemodialysis patients, 15 non-dialysis patients with chronic kidney disease and 14 healthy controls by ELISA (Hycult; HK374-02). Additionally, sCD59 and sC5b-9 were assessed in the peritoneal dialysate.ResultssCD59 and sC5b-9 were detectable in the peritoneal dialysate of all patients, and marginally correlated (r = 0.27, P = 0.06). Plasma sCD59 levels were significantly higher in PD patients than in patients with chronic kidney disease and healthy controls, but did not differ from hemodialysis patients. During follow-up, 19% of PD patients developed peritoneal membrane failure and 27% of PD patients developed loss of residual renal function. In adjusted models, increased sCD59 levels in the dialysate (HR 3.44, 95% CI 1.04-11.40, P = 0.04) and in plasma (HR 1.08, 95% CI 1.01-1.17, P = 0.04) were independently associated with the occurrence of peritoneal membrane failure. Higher plasma levels of sCD59 were also associated with loss of residual renal function (HR 1.10, 95% CI 1.04-1.17, P < 0.001).ConclusionsOur study suggests that sCD59 has potential as a biomarker to predict peritoneal membrane function and loss of residual renal function in PD, thereby offering a tool to improve patient management.
| S-EPMC8192357 | 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:Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications. Combining clinical and peritoneal transport data with the measurement of molecular biomarkers, such as the chemokine CCL18, would improve the complex diagnosis and management of PMF. We measured CCL18 levels in 43 patients' effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by retrospective longitudinal study, and evaluated their association with PMF/EPS development and peritoneal risk factors. To confirm the trends observed in the longitudinal study, a cross-sectional study was performed on 61 isolated samples from long-term (more than 3 years) patients treated with PD. We observed that the patients with no membrane dysfunction showed sustained low CCL18 levels in peritoneal effluent over time. An increase in CCL18 levels at any time was predictive of PMF development (final CCL18 increase over baseline, p = .014; and maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF (odds ratio 4.3; 95% CI 0.90-20.89; p = .067). Moreover, CCL18 levels in effluent at year 3 of PD were independently associated with a risk of PMF development, adjusted for the classical (water and creatinine) peritoneal transport parameters. These trends were confirmed in a cross-sectional study of 61 long-term patients treated with PD. In conclusion, our study shows the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to predict PMF and suggests CCL18 as a new marker and mediator of this serious condition as well as a new potential therapeutic target.
| S-EPMC5393879 | biostudies-literature
Project description:We performed a network meta-analysis of randomised controlled trials (RCTs) and non-randomised studies in adult peritoneal dialysis patients to evaluate the effects of specific renin-angiotensin aldosterone systems (RAAS) blockade classes on residual kidney function and peritoneal membrane function. Key outcome parameters included the following: residual glomerular filtration rate (rGFR), urine volume, anuria, dialysate-to-plasma creatinine ratio (D/P Cr), and acceptability of treatment. Indirect treatment effects were compared using random-effects model. Pooled standardised mean differences (SMDs) and odd ratios (ORs) were estimated with 95% confidence intervals (CIs). We identified 10 RCTs (n = 484) and 10 non-randomised studies (n = 3,305). Regarding changes in rGFR, RAAS blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) were more efficacious than active control (SMD 0.55 [0.06-1.04] and 0.62 [0.19-1.04], respectively) with the protective effect on rGFR observed only after usage ≥12 months, and no differences among ACEIs and ARBs. Compared with active control, only ACEIs showed a significantly decreased risk of anuria (OR 0.62 [0.41-0.95]). No difference among treatments for urine volume and acceptability of treatment were observed, whereas evidence for D/P Cr is inconclusive. The small number of randomised studies and differences in outcome definitions used may limit the quality of the evidence.
| S-EPMC6925258 | biostudies-literature
Project description:The impact of PDF supplementation with alanyl-glutamine (AlaGln) on peritoneal immune-competence in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36) was tested by relating functional test results to transcriptome changes (RNAseq and miRNA analysis) in PD effluent cells.
2018-01-25 | E-MTAB-5462 | biostudies-arrayexpress
Project description:The impact of PDF supplementation with alanyl-glutamine (AlaGln) on peritoneal immune-competence in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36) was tested by relating functional test results to transcriptome changes (RNAseq and miRNA analysis) in PD effluent cells.
2018-01-25 | E-MTAB-5461 | biostudies-arrayexpress
Project description:BackgroundThe prevalence of osteopenia and osteoporosis is higher in patients with chronic kidney disease than that in the general population. Although physical exercise prevents bone loss in hemodialysis (HD) patients, previous studies have not focused on peritoneal dialysis (PD) patients. Therefore, we aimed to evaluate the effects of home-based exercise on bone mineral density (BMD) in patients with PD.MethodsStable outpatients undergoing PD were randomly assigned to the intervention group (n = 26; male, 20; median age, 66 years) or usual-care group (n = 27; male, 21; median age, 64 years). Patients in the intervention group performed home-based exercises (resistance exercise, stretching, and aerobic exercise such as walking) for 6 months, whereas those in the usual-care group performed stretching and their usual physical activity. Based on dual X-ray absorptiometry, the primary outcomes were the BMD data of the lumbar spine and proximal femoral neck. Secondary outcomes included physical function and physical activity. Pre- and post-intervention values were compared.ResultsThere was no significant within-group change in the BMD of the lumbar spine, femoral neck, and hip after 6 months of the exercise program. The intervention group had significantly improved 30-s chair-stand test, 6-min walk test, and physical activity results.ConclusionsHome-based exercises in patients with PD did not improve BMD at any of the sites evaluated. Improvement in physical function and physical activity may reduce the risk of falls in patients with PD.Trial registrationUMIN Clinical Trials Registry, UMIN000041678 . Registered September 4, 2020; retrospectively registered.
| S-EPMC7977172 | biostudies-literature
Project description:In peritoneal dialysis (PD) patients, fungi and Pseudomonas aeruginosa are considered important causative microorganisms for peritonitis with poor prognosis. Our objective was to explore expressions of membrane complement (C) regulators (CRegs) and tissue injuries in the peritoneum of patients with PD-related peritonitis, including fungal and Pseudomonas aeruginosa peritonitis. In peritoneal biopsy tissues obtained at PD catheter removal, we investigated the severity of peritonitis-associated peritoneal injuries and the expression of CRegs, CD46, CD55, and CD59 against peritoneal tissues without any episode of peritonitis. In addition, we evaluated peritoneal injuries among fungal and Pseudomonas aeruginosa-peritonitis (P1) and Gram-positive bacterial peritonitis (P2). We also observed deposition of C activation products such as activated C and C5b-9 and measured sC5b-9 in the PD fluid of patients. As a result, the severity of peritoneal injuries correlated inversely with the expression of peritoneal CRegs. Peritoneal CReg expression in peritonitis was significantly reduced compared to no peritonitis. Peritoneal injuries were more severe in P1 than in P2. CReg expression was further decreased and C5b-9 further increased in P1 than in P2. In conclusion, severe peritoneal injuries due to fungal and Pseudomonas aeruginosa-peritonitis decreased CReg expression and increased deposition of activated C3 and C5b-9 in the peritoneum, suggesting that peritonitis, particularly fungal and Pseudomonas aeruginosa-peritonitis, might induce susceptibility to further peritoneal injuries due to excessive C activation.
| S-EPMC10252763 | biostudies-literature
Project description:BackgroundWe have compared the effects of conventional lactate-based peritoneal dialysis fluid (CPDF) with respect to bicarbonate/lactate-based fluid on peritoneal ultrafiltration (UF) and peritoneal permeability, and on variations on gene expression in cells isolated from effluents of patients' peritoneal bags.MethodsThis was a non-randomized sequential prospective study including all incident peritoneal dialysis (PD) patients (n = 40) recruited in our centre. Peritoneal equilibration tests (PETs) were performed using CPDF or BPDF both containing 2.27% glucose during a 48-h interval in four different sequences. Gene expression variation of selected genes was measured by reverse transcription polymerase chain reaction in mesothelial cells obtained from the total drained fluid during the PET.ResultsIn the overall study, the use of BPDF was associated with significantly lower mass transfer area coefficient for urea and creatinine, longer accelerated peritoneal examination test times for urea and creatinine, lower total pore area available for exchange over diffusion distance and lower UF. There were no differences in the gene expression of aquaporins 1-3, endothelial and inducible nitric oxide synthase (NOS3 and NOS2), or interleukin-6. The SNAIL and E-CADHERIN gene expression normalized ratio was evaluated in peritoneal effluents of cells obtained from CPDF and BPDF. We observed that the SNAIL/E-CADHERIN mRNA ratio decreased when the dialysis sequence started with BPDF and went on to CPDF, but not when the sequence was the opposite.ConclusionThis study shows that those patients who started PD treatment with BPDF were characterized by a better biocompatibility profile. BPDF associates with lower peritoneal permeability to small molecules and lower UF.
| S-EPMC6275447 | biostudies-literature