Peritoneal Membrane Transport Research Articles

Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data.

Background and Objectives: Peritoneal dialysis (PD) is a renal replacement therapy modality in which the dialysis dose can be individually adapted according to the patients' residual kidney function (RKF). RKF is a crucial factor for technique and patient survival. Pharmacological strategies aimed at slowing the loss of RKF in patients on PD are limited. Therefore, we aimed to assess the potential effects and safety of sodium-glucose cotransporter 2 (SGLT-2) inhibitors on the preservation of RKF in patients with and without type 2 diabetes mellitus (T2DM) on PD during an average follow-up of 6 months. Materials and Methods: In this retrospective observational, single-center study on real-world data, we included patients from the Peritoneal Dialysis Unit of the Hospital General Universitario de Ciudad Real, who started treatment with SGLT-2 inhibitors during the period from December 2022 to December 2023. Data on analytical and clinical parameters, RKF, and peritoneal membrane transport function were retrospectively collected at months 0, 3, and 6. Results: Out of 31 patients in our unit, 16 prevalent patients initiated treatment with SGLT-2 inhibitors (13 empagliflozin and 3 dapagliflozin). A total of 62.5% were male and the mean age was 67.3 years. The baseline peritoneal ultrafiltration was higher in the non-diabetic patient (NDMP) group than in the diabetic patient (DMP) group. However, the residual diuresis volume, 24 h residual renal clearance rate of urea in urine, and 24 h proteinuria were higher in the DMP group than in the NDMP group. At the sixth month, patients in both groups preserved RKF and diuresis, with a trend towards a non-significant reduction in proteinuria and blood pressure. Only two patients of the DMP group presented adverse effects. Conclusions: The use of SGLT-2 inhibitors in our sample of patients with and without T2DM on PD appears to be safe and effective to preserve RKF.

#2253 The gender influence on peritoneal membrane transport

Abstract Background and Aims The classification of peritoneal dialysis (PD) patients based on their peritoneal transport was introduced by Twardowski in 1987, analysing a cohort of 86 PD patients, where gender was not specified. Method Aiming to analyze gender differences in the interpretation of peritoneal transport outcomes, we completed a single-center cross-sectional study of 143 incident patients in PD between 2015 and 2022. We also, assessed differences in their follow-up outcomes until PD cessation (21.2 ± 17 months). Results We analyzed 143 patients (55.3 ± 15.5 years, 92% hypertension, 25.5% diabetic, Charlson index 5.9 ± 2.4 points), corresponding to 85 men (M) and 58 women (W). M were older (M 56.4 ± 15.4 years vs. W 53.7 ± 15.7 years, NS) and associated higher comorbidity (hypertension M 95.8% vs. W 86.4%, p = 0.04 and diabetes M 33.7% vs. W 13.6%, P = 0.007, NS on Charlson index) compared to W. Creatinine transport in W is slower than in M (D/P Cr M 0.73 ± 0.1 vs W 0.69 ± 0.1, p = 0.017), but no differences in glucose transport were observed. Although most patients were classified as medium-high transporters, the percentage of M was significantly higher than W (H 71.1% vs M 52.6%). In our cohort, initial adequacy tests using incremental PD reveal that W have a higher total Kt/v (M 2.2 ± 0.5 vs W 2.8 ± 1.9, p = 0.021) attributed to a higher peritoneal Kt/v (M 0. 95 ± 0.41 vs. W 1.3 ± 1.1, p = 0.035) and renal Kt/v (NS). Despite W presented lower residual renal function (NS) and lower residual diuresis (H 1.5 ± 0.7 L vs. M 1.3 ± 0.6 L) compared with M. There was no gender difference in average duration of PD (M 22.4 vs. W 21.5 months). However, most W ended PD to receive a kidney transplant (46.8%), while most M transitioned to haemodialysis (41.3%). Nineteen patients died during follow-up, with 68.4% being M (NS). Conclusion Differences in D/P Cr and normal distribution curves between M and W suggest significant differences in peritoneal membrane transport. Classical methods of assess PD quality and adequacy may need to be corrected by gender, further studies are needed to determine these differences.

Role of endothelial hyaluronan in peritoneal membrane transport and disease conditions during peritoneal dialysis

Peritoneal membrane dysfunction in peritoneal dialysis (PD) is primarily attributed to angiogenesis; however, the integrity of vascular endothelial cells can affect peritoneal permeability. Hyaluronan, a component of the endothelial glycocalyx, is reportedly involved in preventing proteinuria in the normal glomerulus. One hypothesis suggests that development of encapsulating peritoneal sclerosis (EPS) is triggered by protein leakage due to vascular endothelial injury. We therefore investigated the effect of hyaluronan in the glycocalyx on peritoneal permeability and disease conditions. After hyaluronidase-mediated degradation of hyaluronan on the endothelial cells of mice, macromolecules, including albumin and β2 microglobulin, leaked into the dialysate. However, peritoneal transport of small solute molecules was not affected. Pathologically, hyaluronan expression was diminished; however, expression of vascular endothelial cadherin and heparan sulfate, a core protein of the glycocalyx, was preserved. Hyaluronan expression on endothelial cells was studied using 254 human peritoneal membrane samples. Hyaluronan expression decreased in patients undergoing long-term PD treatment and EPS patients treated with conventional solutions. Furthermore, the extent of hyaluronan loss correlated with the severity of vasculopathy. Hyaluronan on endothelial cells is involved in the peritoneal transport of macromolecules. Treatment strategies that preserve hyaluronan in the glycocalyx could prevent the leakage of macromolecules and subsequent related complications.

Association between protein energy wasting and peritoneal membrane transport in peritoneal dialysis.

fast peritoneal transport (FT) has been associated with peritoneal albumin loss and protein energy wasting (PEW); however, this relationship has not been fully studied. the aim of this study was to analyze the differences in nutritional parameters between fast-transport peritoneal membrane (FT-PET) and slow-transport peritoneal membrane (ST-PET), and analyze the association between FT-PET and PEW in peritoneal dialysis (PD) patients. a cross-sectional study of patients on PD. Peritoneal transport characteristics were assessed using the peritoneal equilibration test (PET). Malnutrition inflammation score (MIS) was used for PEW identification. Clinical and biochemical characteristics between patients with and without PEW were assessed. Association between FT-PET status and PEW were evaluated using univariate and multivariate logistic regression. a total of 143 patients were included. FT-PET group showed a higher prevalence of hypoalbuminemia, edema, lower phase angle, lower energy intake, and higher values of MIS score. FT-PET was significantly associated with PEW on univariate (OR: 3.5, 95 % CI: 1.56-7.83, p = 0.002) and multivariate models (OR: 2.6, 95 % CI: 1.02-6.6, p = 0.04). This association was maintained in patients where baseline PET was performed after initiating PD therapy (OR: 6.2, 95 % CI: 1.01-38.6, p = 0.04). FT-PET is associated with PEW evaluated by MIS score. Clinical trials to study nutritional interventions personalized to peritoneal-membrane transport characteristics should be designed.

#6690 THE ASSOCIATION BETWEEN SERUM CHEMERIN AND PERITONEAL MEMBRANE TRANSPORT FUNCTION IN INCIDENT PERITONEAL DIALYSIS PATIENTS: A PROSPECTIVE COHORT STUDY

Abstract Background and Aims Some biomarkers in drained dialysate or peritoneal membrane have been found related to the dialysate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays roles in inflammation, adipogenesis and metabolism. In this study, we intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients. Method This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test (PET) after PD for 4–6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay (ELISA). The patients’ CVDs were recorded during the follow-up period. Results 151 eligible patients with a mean age of 46.59±13.52 years were enrolled. And the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was found to be positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (HDL) (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 vs 27.37 ng/mL, p = 0.000). And there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42% vs 21%, p = 0.009). Conclusion Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of peritoneal membrane. And serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.

INCIDENCE, CLINICAL OUTCOME AND CHANGES OF PERITONEAL MEMBRANE TRANSPORT STATUS IN TREATED CONTINUOUS AMBULATORY PERITONEAL DIALYSIS (CAPD) RELATED PERITONITIS

Peritoneal dialysis-related peritonitis remains the most common complication and a key barrier to peritoneal dialysis’ long-term success. The present study aimed to report on the incidence of peritonitis and clinical outcomes in CKD patients on CAPD at a hospital in Vietnam’s south and evaluate the peritoneal membrane transport status before and after peritonitis therapy. This study was a cross-sectional study involving 141 participants sampled from the warded adult patients at An Giang center general hospital, in Vietnam. Peritonitis rate was measured in terms of incidences per patient-year. Dialysis fluid was drawn under aseptic conditions and treated using a culture approach to identify bacteria. The response treatment time for each episode of peritonitis after receiving empirical antibiotic medication. We use Peritoneal Equilibration Test (PET) to determine the peritoneal transport status. Peritonitis was found in 29.8% of the cases. The number of episodes of peritonitis per patient-year was 0.035. Negative bacteria account for 81.0 percent of all cases tested. It took an average of 3 to 5 days for a clinical response. Before and after peritonitis, there was no statistically significant connection between transport status groups. The rate of peritonitis identified in this study was significantly lower than that recommended by the International Society for Peritoneal Dialysis (ISPD) recommendations. More research is needed to fully understand the variables that influence the clinical outcomes of peritonitis and the remaining function of the peritoneal membrane.

Effects of sitagliptin on peritoneal membrane: The potential role of mesothelial cell tight junction proteins.

The roles of tight junction (TJ) proteins in peritoneal membrane transport and peritoneal dialysis (PD) require further characterisation. Dipeptidyl peptidase-4 is expressed in mesothelial cells, and its activity may affect peritoneal membrane function and morphology. Human peritoneal mesothelial cells (HPMCs) were isolated and cultured from omentum obtained during abdominal surgery, and paracellular transport functions were evaluated by measuring transmesothelial electrical resistance (TMER) and dextran flux. Sprague-Dawley rats were infused daily with 4.25% peritoneal dialysate with and without sitagliptin administration for 8 weeks. At the end of this period, rat peritoneal mesothelial cells (RPMCs) were isolated to evaluate TJ protein expression. In HPMCs, the protein expression of claudin-1, claudin-15, occludin and E-cadherin was decreased by TGF-β treatment but reversed by sitagliptin co-treatment. TMER was decreased by TGF-β treatment but improved by sitagliptin co-treatment. Consistent with this, dextran flux was increased by TGF-β treatment and reversed by sitagliptin co-treatment. In the animal experiment, sitagliptin-treated rats had a lower D2/D0 glucose ratio and a higher D2/P2 creatinine ratio than PD controls during the peritoneal equilibration test. Protein expression of claudin-1, claudin-15 and E-cadherin decreased in RPMCs from PD controls but was not affected in those from sitagliptin-treated rats. Peritoneal fibrosis was induced in PD controls but ameliorated in sitagliptin-treated rats. The expression of TJ proteins including claudin-1 and claudin-15 was associated with transport function both in HPMCs and in a rat model of PD. Sitagliptin prevents peritoneal fibrosis in PD and can potentially restore peritoneal mesothelial cell TJ proteins.

The Association between Serum Chemerin and Peritoneal Membrane Transport Function in Patients Undergoing Incident Peritoneal Dialysis: A Prospective Cohort Study

Introduction: Some biomarkers in drained dialyzate or peritoneal membrane have been found related to the dialyzate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays important roles in inflammation, adipogenesis, and metabolism. We intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients. Methods: This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test after PD for 4–6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay. The patients’ CVDs were recorded during the follow-up period. Results: 151 eligible patients with a mean age of 46.59 ± 13.52 years were enrolled, and the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 ng/mL vs. 27.37 ng/mL, p = 0.000), and there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42 vs. 21%, p = 0.009). Conclusions: Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of the peritoneal membrane, and serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.

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

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

MO706: The Peritoneal Equilibration Test at the Start of Peritoneal Dialysis and Patient Outcome. Analysis in the Presence of Competing Events

Abstract BACKGROUND AND AIMS The success of peritoneal dialysis (PD) depends on the integrity of the peritoneal membrane. The most common peritoneal functional alteration is an impaired ultrafiltration caused by fast peritoneal solute transfer rate. This situation can be present at start of PD and compromise the durability of the membrane through the stay on PD. If the patient leaves PD for another reason, as in the case of a kidney transplant, it affects the probability of a membrane dysfunction appearance. It is known as a competitive event. The aim of this study was to determine whether baseline peritoneal transport status was a risk factor of mortality and technique failure in a cohort of Spanish PD patients using a statistical competing risk model. METHOD The multicenter retrospective cohort study included adult patients of the Levante Registry PD Work Group in Spain who started PD between February 1993 and June 2020. All patients needed to have a peritoneal equilibration test (PET) performed within the first 6 months after PD start. Patients were followed until technique failure, transplantation, renal function recovery, death, or until September 2020. Peritoneal transport status was considered both as a continuous (D/PCr4h) and as a categorical variable, according to the four groupings of D/PCr values defined by Twardoski. We analysed the effect of peritoneal transport over mortality, peritonitis and technique failure by a competing risk model. Kidney transplantation and renal function recovery were considered competing events. RESULTS A total of 4848 patients were enrolled. Baseline PET measurements were available in 2.307 (47.6%). The median follow-up time was 22.2 months (IQR 11.5–40.5). The main characteristics according to the peritoneal transport status are summarized in Table 1. When peritoneal membrane transport was analysed as a continuous variable, D/PCr was an independent risk factor of technique failure. The hazard ratio subdistribution for technique failure was 1.08 [(1.01; 1.16), P-value = 0.018] for every 0.1 increase in D/P Cr ratio. This effect disappeared when the use of icodextrin was included in the model. Baseline peritoneal transport was not associated with a higher mortality or peritonitis risk. CONCLUSION Basal peritoneal transport rate is an independent risk factor for death-censored technique failure in the Levante DP incident population. The use of icodextrin in these patients seems to mitigate this negative effect and may improve the outcomes in PD in patients with initial fast transport. Conventional methods for survival analysis ignoring the competing events may be inappropriate this cohort of patients.

FC089: The Absence of Sting Prevents Peritoneal Damage in a Murine Model of Peritoneal Fibrosis

Abstract BACKGROUND AND AIMS Peritoneal dialysis (PD) is the current replacement therapy for end-stage renal disease (ESRD) patients until renal transplantation can be achieved. However, chronic exposure to non-physiological PD fluids (PDF) and occasional infection episodes may lead to peritoneal damage and membrane transport failure. Chronic inflammation, together with mesothelial-to-mesenchymal transition (MMT) and submesothelial fibrosis, is a hallmark of PDF-associated peritoneal damage whose intrinsic mechanisms are still expected to be disclosed [1–2]. Activation of the innate immunity is the cornerstone for infectious agents’ elimination, also enrolled in response to damage-associated molecular patterns (DAMPs) released from stressed or injured host cells. Leakage of DNA from stressed mitochondria and damaged genomic DNA may act as DAMPs that are recognized by cytosolic double-strand DNA sensors, like the stimulator of interferon gene (STING), to mount an inflammatory response [3]. Excessive activation of STING is involved in autoinflammatory, autoimmune, and increasingly related to several chronic inflammatory conditions [4]. Thus, this study aimed to investigate the role of STING in experimental peritoneal damage. METHOD We induced peritoneal fibrosis in wild-type and STING-KO mice by intraperitoneal administration of 0.1% chlorhexidine gluconate (CHX) daily for 4 weeks. No treated WT and STING-KO mice were used as control. Then, mice were euthanized, and peritoneal tissue and peritoneal lavage fluids were recollected for the following experiments. STING mRNA (Tmem173) and protein levels in control and CHX-treated wild-type were measured by RT-qPCR, western blot and immunohistochemistry. Peritoneal levels of the STING downstream proteins TBK1 and IRF3 and their phosphorylated isoforms were assayed by western blot. Peritoneal membrane thickness was measured in formalin-fixed paraffin-embedded tissues stained with Masson's trichrome stain. Fibronectin protein levels were evaluated by western blot and MMT, fibrosis, and inflammation markers were determined by RT-qPCR. Inflammatory cells present in peritoneal effluents were assayed by flow cytometry. RESULTS We found that in the peritoneum of CHX-treated wild-type mice both Tmem173 expression and STING protein levels were increased. Interestingly, STING-positive cells were located in areas of peritoneal thickness and immune infiltration. Moreover, the protein levels of IRF3, p-IRF3, TBK1 and p-TBK1 were increased, indicating that the STING pathway is activated in experimental peritoneal damage. In STING-KO mice, CHX-induced peritoneal damage was prevented. STING-KO mice under CHX treatment showed decreased peritoneal membrane thickness and attenuated CHX-induced expression of fibrosis and MMT markers, such as Tgb1, Snai1, Cdh2, Col1a1, Fn1 and fibronectin protein when compared with CHX-treated WT mice. The absence of STING also prevented the gene expression of cytokines (Il1b, Il6 and Ifng) and chemokines (Ccl5, Ccl2 and Ccl19) and macrophages infiltration into the peritoneum. Inflammatory cell recruitment into the peritoneal cavity was also decreased in STING-KO mice, including CD3+CD4+ lymphocytes and CD11b+F4/80+ macrophages. CONCLUSION In summary, STING absence prevents peritoneal membrane thickness, fibrosis, and inflammation induced by CHX in a mice model. These results suggest that STING plays a key role in peritoneal membrane injury. Therefore, STING may become a new potential therapeutic target in PD-associated peritoneal damage.

MO720: Elevated Dialysate IL-6 Concentrations are Prospectively Associated with Impaired TLR-Stimulated Cytokine Release from Peritoneal Cells—a Longitudinal Cohort Study

Abstract BACKGROUND AND AIMS Infectious complications and peritoneal inflammation occurring in a significant proportion of PD patients lead to progressive peritoneal membrane injury and account for most peritoneal dialysis (PD) technique failures. Reduced peritoneal immune-competence, caused by the continuous exposure to PD fluids, has been described as a therapy-related pathomechanism. We therefore hypothesized a relationship between dialysate interleukin 6 (IL-6) concentrations and peritoneal host defense. We established an ex vivo stimulation assay to test host defense mechanisms in only 9 mL of PD effluent. The aim of this study was to analyse basal inflammation and immune-competence in the PD population at routine conditions to evaluate the assay as surrogate parameter of immune competence and linking it to PD vintage and clinical outcome parameters. METHOD We prospectively analysed 195 serial routine peritoneal equilibration tests (PETs) of 123 stable PD patients treated exclusively with low-GDP, multi-chamber PD fluids during the glucose dwells and compared the data to routine follow-up clinical data. The cohort represents 76% of all eligible PD patients treated between April 2013 and September 2020 at the local Department of Nephrology. The study was approved by the local ethics committee and was conducted in accordance with the Declaration of Helsinki. All participants underwent a standardized 4-h PET with 3.86% glucose PDF as routine follow-up to test peritoneal membrane transport function, with an additional ex vivo cell stimulation protocol. PD effluent samples were obtained at the 1- and 4-h PET timepoints and immediately processed. Effluent samples were collected directly from the drainage bags into standard 9 mL additive-free sample tubes. For ex vivo stimulation, 100 ng/mL toll-like receptor (TLR) 4 agonist LPS and TLR2 agonist Pam3Cys were added to the effluent in the 9 mL collection tubes in duplicates and incubated at 37°C for 24 h. Unstimulated samples kept in parallel were used as controls. IL-6 concentrations were measured with ELISA in the supernatants. RESULTS Patients were stratified into two cohorts (incident and prevalent) at 120 days of continuous PD therapy. The cohorts were statistically indistinguishable except for stratification-specific variables. During a total follow-up period of 2499 patient-months, 55 patients underwent repeated PETs. Ex vivo stimulation of peritoneal cells significantly increased the IL-6 release 20-fold compared to unstimulated controls and resulted in a dwell-time dependent increase, with a significant lower cytokine released at the 1 h PET timepoint. To assess local inflammation, IL-6 concentrations in PD effluent of the 4 h PET were analysed. PD effluent IL-6 concentrations from the entire study cohort or from incident and prevalent patient subcohorts correlated neither with patient characteristics, RRF, disease background (including prior peritonitis) nor with time on PD. Effluent IL-6 concentrations correlated significantly with markers of systemic inflammation, serum CRP and albumin, with PSTR and with peritoneal protein loss. Interestingly, effluent IL-6 concentrations also had predictive value for risk of a subsequent peritonitis episode during follow-up. Effluent IL-6 levels were, in contrast, negatively correlated with ex vivo–stimulated IL-6 release from PD effluent cells, most remarkably in PD patients with history of prior peritonitis. CONCLUSION This longitudinal study provides the first direct evidence in PD patients of a correlation between peritoneal inflammation and impaired peritoneal immune cell function, likely driving infectious complications. Our study results suggest a mechanistic link between peritoneal inflammation and host defense that may foster innovative therapeutic approaches to improve clinical outcomes of chronic PD.

MO670: Angiotensin Converting Enzyme Blockers, Angiotensin Receptor Blockers and Statins are Associated with a Reduction of Inflammation Markers Without Modification of the Peritoneal Membrane Transport Status in Peritoneal Dialysis

Abstract BACKGROUND AND AIMS Therapy with angiotensin converting enzyme inhibitors (ACE) and angiotensin receptor blockers (ARB) as well as statins might protect the peritoneal membrane and vessels in peritoneal dialysis. The aim of this study was to analyse the effect of treatment on peritoneal transport and inflammation markers. METHOD The first two peritoneal equilibration tests in adult peritoneal dialysis patients, respectively, 6 and 12 months after dialysis start, were analysed for this retrospective study. Use of ACE, ARB and statins was registered. Serum C reactive protein (sCRP), blood leukocyte and platelet count were used as inflammation markers. Data sets of 220 examinations were acquired. Mann–Whitney U-test was performed for the comparison of therapy groups. Median patient age was 67 years. RESULTS A total of 84 measurements (38.2%) were without ACE and ARB, whereas 93 measurements (423%) without statins. Dialysate to plasma (D/P) creatinine in patients without ACE, ARB and statins was 0.64 (all median values, n = 41), respectively, in patients under therapy with ACE, ARB and statins 0.66 (n = 52). Use of ACE and ARB without statins resulted in D/P creatinine 0.64 (n = 54), whereas use of statins alone in D/P creatinine 0.63 (n = 48). The difference between groups was statistically not significant. There was a tendency of higher values of D/P creatinine (median 0.68) in patients under therapy with ACE and statins (Fig. A). sCRP was higher in patients without ACE, ARB and statins compared to patients with ACE, ARB or statins (0.60 versus 0.30 mg/dL, P &amp;lt; 0.05) (Fig. B). Furthermore platelet count was slightly higher in patients without ACE, ARB and statins (25 8000 versus 22 6000/mm3). Blood leukocyte count did not present significant differences (median values 6930 to 6855/mm3). CONCLUSION Our data suppose the absence of a protective effect of ACE, ARB and statins on peritoneal transport expressed by P/D creatinine despite reduced signs of systemic inflammation.

Baseline Peritoneal Membrane Transport Characteristics Are Associated with Peritonitis Risk in Incident Peritoneal Dialysis Patients.

The peritoneal equilibration test (PET) is a semi-quantitative measurement that characterizes the rate of transfer of solutes and the water transfer rate across the peritoneum in patients treated with peritoneal dialysis (PD). The results of the PET are used to maximize daily peritoneal ultrafiltration and solute clearances. Previous studies have shown that high transport status is associated with ultrafiltration failure, malnutrition, and reduced survival; however, the way in which peritoneum transport characteristics affect peritonitis risk is unknown. In the current cohort study, we recruited 898 incident-PD patients and used intention-to-treat analysis to test if baseline PET affected the subsequent 3-year peritonitis rate. Among all recruited PD patients, 308 (34.2%) developed peritonitis within three years. Multivariate Cox regression analysis showed that the high-transport group has the greatest peritonitis risk (HR 1.98, 95% CI: 1.08–3.62) even after an adjustment for demographics, comorbid diseases, and biochemical measurements. We concluded that a baseline high peritoneal membrane transport rate is an independent risk factor for peritonitis in incident PD patients.

The Effect of Far-Infrared Therapy on the Peritoneal Membrane Transport Characteristics of Uremic Patients Undergoing Peritoneal Dialysis: An Open-Prospective Proof-of-Concept Study.

Long-term peritoneal dialysis (PD) can lead to detrimental changes in peritoneal membrane function, which may be related to the accumulation of glucose degradation products. A previous study demonstrated that 6 months of far-infrared (FIR) therapy may decrease glucose degradation products in PD dialysate. Due to limited literature on this matter, this study aims to investigate the effect of FIR therapy on the peritoneal membrane transport characteristics of PD patients. Patients were grouped according to baseline peritoneal transport status: lower transporters (low and low-average) and higher transporters (high-average and high). Both groups underwent 40 min of FIR therapy twice daily for 1 year. In lower transporters, FIR therapy increased weekly dialysate creatinine clearance (6.91 L/wk/1.73 m2; p = 0.04) and D/P creatinine (0.05; p = 0.01). In higher transporters, FIR therapy decreased D/P creatinine (−0.05; p = 0.01) and increased D/D0 glucose (0.05; p = 0.006). Fifty percent of high transporter patients shifted to high-average status after FIR therapy. FIR therapy may decrease D/P creatinine for patients in the higher transporter group and cause high transporters to shift to high-average status, which suggests the potential of FIR therapy in improving peritoneal membrane function in PD patients.

MO710GALECTIN-3, IS IT A NEW PLAYER IN PERITONEAL INFLAMMATION AMONG PATIENTS UNDERGOING PERITONEAL DIALYSIS?

Abstract Background and Aims Peritoneal dialysis (PD) is a common used method for renal replacement therapy. Prolonged PD treatment causes structural and functional changes in the peritoneal membrane which are attributed to local inflammatory process in the peritoneal cavity. Galectin-3 (Gal-3) is a galactoside-binding lectin with pro-inflammatory and pro-fibrotic effects. The aim of this study was to assess correlation between Gal-3 serum and dialysate effluent levels with peritoneal membrane transport characteristics. Method Gal-3 levels in serum and dialysate effluent were measured simultaneously in prevalent PD patients in morning visit or during peritoneal equilibration test (PET). Gal-3 levels were correlated with clinical and laboratory parameters. Interlukin (IL) -6 levels were measured in dialysate effluent. Gal-3 mRNA and protein expression were evaluated after exposure of primary endothelial cell culture to several dialysate solutions. Results 37 PD patients were included in the study; mean age was 65.7±13.1 years, mean dialysis vintage was 17.5±13 months. Gal-3 levels in dialysate effluent correlated with peritoneal equilibration test (PET) results (0.663, p=0.005) and effluent IL-6 levels (0.674, p=0.002) but not with serum Gal-3 levels or dialysis vintage. Patients with high PET results had higher effluent Gal-3 levels as compared average low PET results. In multivariate regression analysis effluent IL-6 level was the most dominant predictor of effluent Gal-3 levels. Gal-3 mRNA and protein expression in primary endothelial cell culture were not affected by stimulation with dialysate solutions. Conclusion Our study demonstrated presence of Gal-3 within the dialysate effluent in PD patients. Gal-3 levels correlated with peritoneal membrane transport characteristics and effluent IL-6 levels suggesting a role in the inflammatory process within the peritoneal cavity.

Peritoneal Membrane Transport Characteristics in Uni-PET with Preceding Icodextrin Dwell as Compared to Classic PET with Preceding Glucose Dwell: A Prospective Study

Peritoneal Membrane Transport Characteristics in Uni-PET with Preceding Icodextrin Dwell as Compared to Classic PET with Preceding Glucose Dwell: A Prospective Study

P1213ROLE OF PERITONEAL PHOSPHORUS TRANSPORT IN PERITONEAL DIALYISIS REGIMEN FOR THE MANAGEMENT OF HYPERPHOSPHATEMIA

Abstract Background and Aims The ratio D/P-Creatinine (DP-Cr) obtained by the peritoneal equilibrium test (PET) is the most widely used parameter to characterize the type of peritoneal membrane transport, and it is used to determine the dialysis regimen for ultrafiltration (UF). It has been suggested that net UF influences the final clearance of solutes, so guiding ultrafiltration by D/P-Phosphorus (DP-P) instead of DP-Cr could have some added value in the management of hyperphosphatemia. The objective of this study is to define if there is a correlation between DP-P and DP-Cr, and if these are related to the clearance of phosphorus (P) and creatinine (Cr). Method retrospective analysis of PETs performed during 2016 and 2017 in our center. DP-Cr and DP-P were calculated, and in patients with 24h effluent sample the day of the PET, it was also analyzed weekly Kt/V-urea, and peritoneal Cr and P clearance (CrCl and PCl, respectively). Statistical analysis was done using t-Student test for independent data and Pearson correlation coefficient, with SPSS Statistical Package program v.23, establishing a significance level of p&amp;lt;0.05. Results 68 PETs were analyzed in 54 patients, mean age 60.4 years (SD 17), predominantly men (69% vs 31%). The mean plasma P, DP-Cr and DP-P were respectively 4.5 mg/dL (SD 1.2), 0.74 (SD 0.12) and 0.71 (SD 0.17). The correlation coefficient DP-P/DP-Cr showed a significant relationship (r=0.84, p&amp;lt;0.001), which was maintained when analyzing patients according to phosphorus levels: DP-P/DP-Cr with P&amp;lt;5 mg/dL (r=0.81); and P≥5 mg/dL (r=0.93) (p&amp;lt;0.001).Patients in DP-P ≥50th percentile had P levels of 4.2 (± 1.05), and those in&amp;lt;50th percentile had levels of 4.88 (± 1.38) (p &amp;lt;0.031). Moreover, in patients with 24h effluent analyzed the day of the PET (n=35), the average PCl and CrCl was 4.1 and 2.85 ml/min, with statistical significant correlation (r=0.92, p&amp;lt;0.001).However, in these patients no relationship was found between DP-Cr and CrCl (r=0.068, p=0.7), nor between DP-P and PCl (r=0.052, p=0.7). Conclusion The DP-P/DP-Cr high correlation suggests that both parameters could be useful to classify the type of peritoneal transport. However, although patients with higher DP-P had better control of hyperphosphatemia, thus suggesting a direct positive relationship between DP-P and PCl, our data showed no correlation between them.

Peritoneal Transport Characteristics at the Beginning and in Long Term Peritoneal Dialysis: a Single Center Experience.

Introduction:Peritoneal dialysis (PD) is an established treatment for patients with end-srage kidney disease. The method was developed as an alternative to hemodialysis (HD) presenting a patient survival rate equivalent to HD and better preservation of residual renal function. Peritoneal dialysis (PD) patients have different peritoneal membrane permeability (transport) characteristics. High peritoneal membrane permeability is associated with increased mortality risk in the patient population.Aim:The aim of this study was to analyze the importance of the peritoneal membrane transport status in patients treated with continuous ambulatory peritoneal dialysis (CAPD).Methods:The study included 60 adult continuous ambulatory peritoneal dialysis (CAPD) patients, 29 male and 31 female, mean age 56.63±15.06 years. All patients treated with conventional glucose- based PD fluids. For the short term (within 3 month after start of PD) and long term (more than 12 months) peritoneal dialysis analysis of peritoneal transport characteristics has been used peritoneal functional test (PFT). With the test, categorisation of patients was possible into high (H), high-average (HA), low average (LA), and low (L) transporters.Results:Dialysate–to plasma ratio (D/P) of creatinine showed significantly increased over time (0.654±0.141 vs... 0.705±0.13, p<0.001). In multivariate analysis age, gender, time on dialysis, comorbid diseases, diabetes mellitus (DM), serum albumin, were considered as independent factors influencing the PFT. The high transporter group had higher D/Pcreat (H 0.84±0.03 vs... LA 0.57±0.05, p<0.001), higher proportion of man (H 100% vs... LA 39.5%, p<0.05), higher proportion of patients with comorbid diseases (H 60% vs... LA 20.9%, p<0.05), lower serum albumin concentration (H 29±6.0 vs... LA 37±5.2, p<0.001), lower D4/D0 glucose ( H 0.23±0.07 vs... LA 0.42±0.14, p<0.001), and lower drained volume (H 600±173 vs... LA 1016±355, p<0.001).Conclusion:The PFT was en easy, inexpensive, reliable test to assess peritoneal transport type and it also provided information about peritoneal clearance of solutes and ultrafiltration. Peritoneal transport type classification was recognized not only as aid for prescription, but also as a prognostic index.

P1149PERITONEAL MEMBRANE CHARACTERISTICS OVER TIME: A LONGITUDINAL STUDY

Abstract Background and Aims Modified PET (use of 3.86% glucose dialysate instead of 2.27%) and temporal drainage at one hour allows a more complete study of peritoneal membrane transport, as it provides information about sodium sieving, free water transport (FWT) and ultrafiltration failure (UFF). Longitudinal data using this PET are sporadic. Aims of our study were a) longitudinal follow-up of the membrane function using modified PET b) evaluation of UFF and association with clinical and membrane characteristics. Method We analyzed all modified PET tests performed in our unit during the last 9 years. Patients who underwent the first test during the first year of treatment and then once a year were included. We estimated classic peritoneal transport parameters like D/P creatinine, D/D0 glucose and ultrafiltration (UF) at 4 hours. Moreover we calculated sodium seiving expressed as Dip/DPNa= (Dialysate sodium time 0/plasma sodium)-(Dialysate sodium time 1 hour/plasma sodium)], sodium removal (in one hour) and FWT. We collected clinical and lab data of the patients too. Results A total of 219 PETs were performed in 85 PD patients, (median age 64 years (range 18-45). The baseline membrane characteristics of the patients were: DP creatinine=0.74±0.11, D/D0glucose=0.28±0.08, DipDPNa=0.05±0.04, sodium removal=29,804 ±26,894 (mmol/L), FWT=214.9±194.7 ml and UF =655.1±265.5 ml. On multivariate regression analysis D/P creatinine, FWT and sodium removal were significant independent covariates accounting for 50% of the variability of ultrafiltration . The patients were followed-up for a median of 36 months (range 2.4-143).For the repeated measurements, the analysis showed that the observed values of D/Pcre,D/D0, Dip/DPNa, FWT and UF remained rather stable across the different time measurements. During the study, 23 out of 85 pts developed peritoneal UF failure (UFF). Analysis was performed using univariate random effects logistic time-series models and only D/D0 (OR=0.84, P=0.001), D/P Cre (OR=1.15, p&amp;lt;0.001), urine volume (OR=1.26, p=0.027) and sodium removal (OR=0.99, p=0.003) were significantly associated with relative risk of UFF development. Conclusion Surprisingly, our patients present a stable membrane function over time. Possible explanations could be the low peritonitis rate and strict use of hypertonic glucose dialysates. Ultrafiltration failure was correlated with higher D/P creatinine and lower D/D0 glucose values, higher baseline urine volume and lower sodium sieving.