Peritoneal Solute Transport Rate Research Articles

Short-term peritoneal rest reduces peritoneal solute transport rate and increases ultrafiltration in high/high average transport peritoneal dialysis patients: a crossover randomized controlled trial

ABSTRACT Background The peritoneal solute transport rate (PSTR) tends to increase over time in some patients undergoing peritoneal dialysis (PD), potentially leading to ultrafiltration (UF) failure. Previous case reports have shown a significant decrease in PSTR and subsequent recovery of UF after discontinuing PD for a while. Therefore, we conducted a randomized controlled crossover study to evaluate the impact of short-term peritoneal rest on PSTR. Methods The study involved 14 continuous ambulatory peritoneal dialysis (CAPD) patients with high/high-average transport rate. Two groups were randomly assigned different treatment sequences: one group underwent daily intermittent peritoneal dialysis (IPD) for 4 weeks followed by CAPD, while the other group initially received CAPD treatment for 4 weeks and then switched to IPD. Peritoneal equilibration tests were performed before and after each treatment to evaluate PSTR and paired t-tests were used to compare the changes. Volume load, serum potassium and other clinical indicators were monitored at the same time. Results Short-term peritoneal rest (daily IPD) significantly reduced PSTR, with a decrease in the dialysate:plasma creatinine ratio from 0.71 ± 0.05 to 0.65 ± 0.07 (P < .001). Additionally, ultrafiltration significantly increased from 210 ± 165 ml to 407 ± 209 ml (P = .001). But there were no significant changes in interleukin-6 and vascular endothelial growth factor of PD effluent. No serious adverse events such as hypotension or hyperkalaemia occurred. Conclusions In PD patients with high and high-average transport, a 4-week period of short-term peritoneal rest by switching from CAPD to IPD (without long dwell) can lead to reductions in PSTR and increases in UF volumes, while maintaining clinical safety.

A retrospective study of baseline peritoneal transport character and left ventricular hypertrophy in incident peritoneal dialysis patients: interrelationship and prognostic impacts

Background Left ventricular hypertrophy is associated with adverse outcomes among peritoneal dialysis patients. The aim of this study was to evaluate the prognostic impact of baseline left ventricular hypertrophy and its relationship with baseline peritoneal transfer characteristics in peritoneal dialysis patients. Methods We enrolled 151 incident peritoneal dialysis patients to perform a multicentric retrospective cohort study since January 1, 2017 to January 31, 2021. Patients were grouped based on baseline dialysate-to-plasma creatinine ratio at 4 h as follows: low (<0.50), low average (0.5–0.64), high average (0.65–0.80) and high (≥0.81). Echocardiography and clinic data were recorded yearly. The Cox proportional hazards models and competing risk model were used to evaluate patients’ survival. Generalized linear mixed models were performed to explore risk factors associated with left ventricular hypertrophy. Results During a median follow-up period of 33 months (range, 16–48 months), 21 (13.9%) patients died, including 16 (10.60%) cardiovascular deaths. Controlling the competing risks of switching to hemodialysis, kidney transplantation and loss to follow-up, baseline left ventricular hypertrophy was an independent risk factor for all-cause mortality (subdistribution hazard ratio, 2.645; 95% confidence interval, 1.156–6.056; p = 0.021). Baseline high and high average transport status were positively related to left ventricular mass index and left atrium diameter 2 years after PD initiation. Conclusion Baseline fast peritoneal solute transport rate may be an effect factor for aggravating left ventricular hypertrophy which predicted poor outcomes for peritoneal dialysis patients. The findings offered important ideas for further prospective intervention study.

Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study

BackgroundThe associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. Subjects and designA total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFβ were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. ResultsA trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r=0.32, p=0.01), MCP-1 (r=0.47, p=0.01), IL-6 (r=0.48, p=0.01). Conversely, no significant correlation was found between D/P Cr and TGF-β (r=0.04, p=0.70), TNF-ɑ (r=0.22, p=0.05), VEGF (r=0.02, p=0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p=0.03). ConclusionElevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment.

The benefits of peritoneal dialysis (PD) solution with low-glucose degradation product in residual renal function and dialysis adequacy in PD patients: A meta-analysis.

The peritoneal effects of low-glucose degradation product (GDP)-containing peritoneal dialysis (PD) solutions have been extensively described. To systematically evaluate the efficacy and safety of low GDP solution for PD patients, specifically the effect on residual renal function (RRF) and dialysis adequacy, we conducted a meta-analysis of the published randomized controlled trials (RCTs). Different databases were searched for RCTs that compared low GDP-PD solutions with conventional PD solutions in the treatment of PD patients with continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). The outcomes of RCTs should include RRF and may include small solute clear-ance, peritoneal transport status, nutritional status, and all-cause mortality. Seven studies (632 patients) were included. Compared with the conventional solution, low-GDP solution preserved RRF in PD patients over time (MD 0.66 mL/min, 95% CI 0.34 to 0.99; p&lt;0.0001), particularly in one year of treatment (p&lt;0.01), and improved weekly Kt/V (MD 0.11, 95% CI 0.05 to 0.17; p=0.0007) without an increased 4-hour D/Pcr (MD 0.00, 95% CI -0.02 to 0.02; p=1.00). Notably, the MD of RRF and urine volume between the two groups tended to decrease as time on PD progressed up to 24 months. Patients using low GDP PD solutions did not have an increased risk of all-cause mortality (MD 0.97, 95% CI 0.50 to 1.88; p=0.93). Our meta-analysis confirms that the low GDP PD solution preserves RRF, improves the dialysis adequacy without increasing the peritoneal solute transport rate and all-cause mortality. Further trials are needed to deter-mine whether this beneficial effect can affect long-term clinical outcomes.

Peritoneal dialysis effluent-derived exosomal miR-432-5p: an assessment tool for peritoneal dialysis efficacy.

BackgroundUltrafiltration (UF) volume and peritoneal solute transport rate (PSTR) are common parameters used to evaluate the efficacy of peritoneal dialysis (PD) on individual patients. It is unclear whether the level of exosomal microRNA (miRNA) in peritoneal dialysis effluent (PDE) can predict UF or PSTR. This study was designed to investigate if there is a correlation between PDE exosomal miRNA (miR-432-5p) levels and various UF volumes and PSTRs in PD patients. It also aimed to explore the underlying mechanism of water and dialytic sodium removal (DSR).MethodsThe PSTR was quantified using the 4-hour (4 h) 3.86% dialysate to plasma creatinine ratio. The PDE exosomes (PDE-exo) were isolated by ultracentrifugation. An miRNA assay was used to identify the different miRNA in the PDE-exo of patients in a high (H; PSTR >0.65, n=5) and low (L; PSTR <0.65, n=5) group. We focused on miR-432-5p as bioinformatic analysis had shown that it could be involved in sodium transport. We used mimic/inhibitor transfection and dual luciferase reporter assay to verify the target genes of miR-432-5p. We used PKH-67 stained PDE-exo to observe their interaction with human MeT-5A mesothelial cells.ResultsOur results showed that the PDE-exo-miR-432-5p level was higher in group H than in group L. The levels of PDE-exo-miR-432-5p were positively correlated with PSTR (r=0.391; P<0.05; n=40) and negatively correlated with the 4 h UF volume (r=−0.376; P<0.05; n=40) and 4 h DSR (r=−0.535; P<0.01; n=24). Epithelial sodium channel α subunit (α-ENaC) was revealed as a direct target gene of miR-432-5p and expressed on both human peritoneum and MeT-5A cells. Furthermore, we found the PKH67 labeled-PDE-exo could be internalized into MeT-5A cells.ConclusionsA high PDE-exo-miR-432-5p level was associated with poor UF volume and DSR. It may be that PDE-exo-miR-432-5p affects DSR through downregulating α-ENaC expression.

Glycoprotein 96 in Peritoneal Dialysis Effluent-Derived Extracellular Vesicles: A Tool for Evaluating Peritoneal Transport Properties and Inflammatory Status.

BackgroundExtracellular vesicles (EVs) from peritoneal dialysis effluent (PDE), containing molecules such as proteins and microRNAs (miRNAs), may be potential biological markers to monitor peritoneal function or injury. Peritoneal inflammation is an important determinant of peritoneal solute transport rate (PSTR). Thus, the aim of this study is to determine whether the specific proteins capable of evaluating the PSTR could be found in PDE-EVs, and explore the underlying mechanism for the association between PSTR and peritoneal inflammation.MethodsSixty patients undergoing peritoneal dialysis (PD) were divided into two groups: high/high average transport (H/A) group (PET >0.65) and low/low average transport (L/A) group (PET <0.65). EVs derived from PDE (PDE-EVs) were isolated by ultracentrifugation. Proteomic analysis was performed to explore the differentially expressed proteins and identify the potential biomarkers in PDE-EVs from the two groups, and we focused on glycoprotein 96 (GP96) as it could be involved in the inflammatory process. The expression of GP96 in PDE-EVs and inflammatory cytokines was quantified by real-time PCR and enzyme-linked immunosorbent assay. The infiltration of macrophages and neutrophils into the peritoneum was detected using immunohistochemistry in a PD rat model.ResultsThe expression of PDE-EVs-GP96 was significantly higher in the H/A group, and was positively correlated with the PSTR and the level of the inflammatory factor interleukin (IL)-6. GP96-enriched EVs enhanced the secretion of proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 in macrophages, which was reversed by a pharmacological GP96-specific inhibitor (PU-WS13). The GP96 inhibitor also reduced local peritoneal inflammation by decreasing the infiltration of inflammatory cells and levels of proinflammatory cytokines (IL-6 and TNF-α) and chemokines (CCL2, CXCL1, and CXCL2) in a PD rat model.ConclusionsPDE-EVs-GP96 is a new promising tool to evaluate the status of peritoneal inflammation and PSTR, and the mechanism may be related to affecting the inflammatory properties of macrophages.

Relationship between peritoneal solute transport and dialysate inflammatory markers in peritoneal dialysis patients: A cross-sectional study

BackgroundThe associated factors of peritoneal small solute transport was not fully understood. This research aimed to investigate the connection between dialysate inflammatory markers (e.g. macrophage migration inhibitory factor, MIF) in peritoneal dialysis (PD) effluent and peritoneal solute transport rate (PSTR) properties. Subjects and designA total of 80 stable PD patients in the First ShaoYang Hospital were enrolled in present study. Overnight PD effluent and serum inflammatory markers including MIF, MCP-1, VEGF, IL-6, TNFα and TGFβ were detected. Pearson correlation analysis and Logistic regression was performed to determine the risk factors for the increased PSTR. ResultsA trend toward increased values of MIF, MCP-1 and IL-6 in PD effluent was observed in subjects with high PSTR when compared with those with low PSTR. The Pearson correlation test showed that D/P Cr exhibited positive correlations with dialysis effluent MIF (r=0.32, p=0.01), MCP-1 (r=0.47, p=0.01), IL-6 (r=0.48, p=0.01). Conversely, no significant correlation was found between D/P Cr and TGF-β (r=0.04, p=0.70), TNF-ɑ (r=0.22, p=0.05), VEGF (r=0.02, p=0.86) and serum inflammatory markers. In the unadjusted regression analysis, dialysis effluent MIF (OR 2.41), MCP-1 (OR 1.72), IL-6 (OR 1.55) were associated with high PSTR condition. Multivariate logistic regression analysis showed that the adjusted odds ratios (OR) of dialysis effluent MIF for high PSTR were 2.47 in all subjects (p=0.03). ConclusionElevated MIF, MCP-1 and IL-6 levels in PD effluent were associated with increased PSTR. Elevated dialysis effluent MIF levels was an independent risk factor for high PSTR in subjects with PD treatment.

The prognosis and risk factors of baseline high peritoneal transporters on patients with peritoneal dialysis.

The relationship between baseline high peritoneal solute transport rate (PSTR) and the prognosis of peritoneal dialysis (PD) patients remains unclear. The present study combined clinical data and basic experiments to investigate the impact of baseline PSTR and the underlying molecular mechanisms. A total of 204 incident CAPD patients from four PD centres in Shanghai between 1 January 2014 and 30 September 2020 were grouped based on a peritoneal equilibration test after the first month of dialysis. Analysed with multivariate Cox and logistic regression models, baseline high PSTR was a significant risk factor for technique failure (AHR 5.70; 95% CI 1.581 to 20.548 p = 0.008). Baseline hyperuricemia was an independent predictor of mortality (AHR 1.006 95%CI 1.003 to 1.008, p < 0.001) and baseline high PSTR (AOR 1.007; 95%CI 1.003 to 1.012; p = 0.020). Since uric acid was closely related to high PSTR and adverse prognosis, the in vitro experiments were performed to explore the underlying mechanisms of which uric acid affected peritoneum. We found hyperuricemia induced epithelial‐to‐mesenchymal transition (EMT) of cultured human peritoneal mesothelial cells by activating TGF‐β1/Smad3 signalling pathway and nuclear transcription factors. Conclusively, high baseline PSTR induced by hyperuricaemia through EMT was an important reason of poor outcomes in CAPD patients.

Effluent Osteopontin levels reflect the peritoneal solute transport rate.

Long-term peritoneal dialysis (PD) is accompanied by low-grade intraperitoneal inflammation and may eventually lead to peritoneal membrane injury with a high solute transport rate and ultrafiltration failure. Osteopontin (OPN) is highly expressed through the stimulation of pro-inflammatory cytokines in many cell types. This study aimed to investigate the potential of OPN as a new indicator of peritoneal deterioration. One hundred nine continuous ambulatory PD patients were analyzed. The levels of OPN and IL-6 in peritoneal effluents or serum were analyzed by ELISA kits. The mean effluent OPN concentration was 2.39 ± 1.87 ng/mL. The OPN levels in drained dialysate were correlated with D/P Cr (p < 0.0001, R = 0.54) and D/D0 glucose (p < 0.0001, R = 0.39). Logistic regression analysis showed that the OPN levels in peritoneal effluents were an independent predictive factor for the increased peritoneal solute transport rate (PSTR) obtained by the peritoneal equilibration test (p < 0.001). The area under the receiver operating characteristic curve of OPN was 0.84 (95% CI: 0.75–0.92) in predicting the increased PSTR with a sensitivity of 86% and a specificity of 67%. The joint utilization of effluent OPN with age, effluent IL-6, and serum albumin further increased the specificity (81%). Thus, OPN may be a useful indicator of peritoneal deterioration in patients with PD.

Associations between dialysate interleukin-6 and Tie-2 and peritoneal solute transport rate and outcomes for patients undergoing peritoneal dialysis: A prospective cohort study.

Objectives:We designed this prospective observational study to clarify the associations between dialysate IL-6, a marker of ongoing peritoneal inflammation, Tie2, an important factor in angiogenesis in the peritoneum, and a high peritoneal solute transport rate (PSTR) in patients undergoing peritoneal dialysis (PD) and to investigate their outcome predictive roles.Methods:A total of 60 stable continuous ambulatory peritoneal dialysis (CAPD) patients from a single center in China were analyzed in this prospective study. We measured dialysate levels of IL-6 and Tie-2 using ELISAs. Our primary study endpoint was all-cause mortality with 10 years’ follow-up.Results:For the evaluation of PSTR, we used the Dialysis/Plasma creatinine (D/Pcr) ratio. We subdivided the patients into two groups for statistical evaluation: low and low average D/Pcr (<0.64; L/A), and high and high average D/Pcr (≥0.65; H/A) transporters. The mean levels of dialysates IL-6 (21.71 ± 8.88 pg/mL) and Tie-2 (1.23 ± 0.43 ng/mL) were significantly higher in the H/A (high and high average, group than those in the L/A group (13.94 ± 5.43 pg/mL, p<0.001 and 0.95 ± 0.43 ng/mL, p=0.019; respectively). Moreover, IL-6 and Tie-2 were positively correlated with D/Pcr (r=0.366, p=0.004 and r=0.402, p=0.001; respectively). Both dialysates IL-6 and Tie-2 were independent determinants of a high peritoneal solute transport rate. After follow-up for 42.65±18.08 months, 30 patients (50.0%) had died. An increased D/Pcr increased the risk of all-cause mortality in patients with CAPD (p=0.018), but the dialysates IL-6 and Tie2 were not independent predictors of all-cause mortality (p>0.05).Conclusion:Our results suggest that patients undergoing CAPD have a high peritoneal solute transport status with local peritoneal inflammation and angiogenesis. Increased D/Pcr is a relative risk factor for mortality and technique failure in patients undergoing CAPD.

Comparison of peritoneal function within the first 1 year of peritoneal dialysis between diabetic and non‐diabetic patients

The aim of this study was to compare the changes in peritoneal function and residual renal function in the first year between diabetic and non-diabetic patients receiving peritoneal dialysis (PD). We extracted 73 incident PD patients (male, 73%; age, 59 ± 15 years) from a previous cohort, and investigated the changes in PD-related parameters, including the dialysate to plasma ratio of creatinine (D/P Cr) and Kt/V. D/P Cr increased in non-diabetics, whereas it did not change significantly in diabetic patients. These differences were more pronounced among icodextrin users. On multivariate analysis, the presence of diabetes was independently associated with the changes in D/P Cr. On the contrary, there was no significant difference in the changes of renal Kt/V between the two groups. A higher peritoneal solute transport rate at the start of PD in diabetics was attenuated within 1 year. Icodextrin is thought to have an important role through improving body fluid status.

Analysis of Factors Influencing the Prognostic Significance of Hyponatremia in Peritoneal Dialysis Patients

Background: The evidence linking low serum sodium levels with the risk of mortality in peritoneal dialysis (PD) patients is controversial. Considering the different mechanisms contributing to hyponatremia in these patients, it is conceivable that the prognostic significance of this factor may vary, according to the clinical setting. Methods: Following a retrospective, observational design, we analyzed the association between hyponatremia and mortality in 748 patients incident on PD. We applied multivariate strategies of analysis, with the main objective of identifying subgroups of patients in whom hyponatremia could sustain different degrees of association with mortality (main outcome variable). For this purpose, we performed preliminary analyses to: (1) disclose predictors of serum sodium levels before and after (mean of first 3 months) initiation of PD (main study variable) and (2) investigate the overall prognostic significance of hyponatremia, in our patients. Results: Comorbidity, hypoalbuminemia, and lower glomerular filtration rate (GFR) were main predictors of hyponatremia. Use of icodextrin was another inverse correlate of serum sodium, and the only consistent predictor of a decline of natremia, once PD was started. Multivariate analysis confirmed early hyponatremia as an independent marker of survival. However, stratified analyses showed that this association was most apparent in specific subsets, namely, hypoalbuminemic, more anemic patients with higher baseline levels of GFR and C-reactive protein and faster peritoneal solute transport rates. Other factors potentially reinforcing the prognostic significance of hyponatremia included lower lean body mass levels, nonprescription of renin-angiotensin-aldosterone system antagonists, and use of icodextrin-based PD solution. On the contrary, baseline overhydration or categorization by classic predictors of mortality (age, comorbidity, diabetes) did not appear to influence the risk pattern associated with lower serum sodium levels. Conclusions: Our results suggest that hyponatremia performs as a consistent correlate of the risk of mortality mainly in PD patients manifesting direct or indirect signs of inflammation and wasting, while this association is not apparently linked to the presence of overhydration or nominal, preexisting comorbid conditions.

Dialysate copeptin and peritoneal transport in incident peritoneal dialysis patients

PurposeSystemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD). Arginine vasopressin (AVP) and its surrogate marker copeptin play important roles in many pathophysiological processes in chronic kidney disease. The aim of this study was to assess if copeptin concentrations in plasma and dialysate were related to peritoneal transport parameters and residual renal function (RRF) in incident PD patients.MethodsIn 37 clinically stable incident PD patients (mean age 50 years, 68% women, 32% diabetes), a 4 h peritoneal equilibration test (PET) was performed 4–6 weeks after the onset of PD. Plasma (at 2 h of PET) and dialysate (at 4 h) concentrations of copeptin, high-sensitivity C-reactive protein and interleukin-6 (IL-6) were determined.ResultsPlasma (80.7 ± 37.3 pg/mL) and dialysate (33.2 ± 18.0 pg/mL) concentrations of copeptin were correlated (Rs = 0.52, p = 0.001). Plasma and dialysate copeptin concentrations were negatively correlated with renal function as assessed by renal Kt/V (Rs = − 0.38; p = 0.021 and Rs = − 0.33; p = 0.047, respectively). At PET, dialysate copeptin negatively correlated with D/P creatinine (Rs = − 0.35, p = 0.033), and positively with D/D0 glucose (Rs = 0.33, p = 0.045) and ultrafiltration (Rs = 0.37, p = 0.024). Multivariate analysis showed that low dialysate copeptin (β = –0.30, p = 0.049) and high dialysate IL-6 (β = + 0.40, p = 0.012) were independent determinants of higher D/P creatinine.ConclusionsDialysate copeptin was negatively associated with D/P creatinine in incident PD patients suggesting a potential influence of copeptin or AVP on peritoneal solute transport rate that might involve vasoactive mechanisms.

Dialysate cell-free mitochondrial DNA fragments as a marker of intraperitoneal inflammation and peritoneal solute transport rate in peritoneal dialysis

BackgroundMitochondrial DNA (mtDNA) released into extracellular subsequent to cell injury and death can promote inflammation in patients and animal models. However, the effects of peritoneal dialysate cell-free mtDNA on intraperitoneal inflammation and peritoneal solute transport rate (PSTR) in peritoneal dialysis (PD) patients remain unclear.MethodsWe select the incident patients who began PD therapy between January 1, 2009, and December 30, 2010. Peritoneal dialysate was collected at the time of peritoneal equilibration test. The cell-free mtDNA, IL-6, IL-17A, TNF-α and IFN-γ were measured. All patients were followed till December 2017. The results were compared with PSTR and patient survival.ResultsOne hundred and eighty-nine patients were included in the study. The average age was 47.1 ± 13.5 years, 55.6% of the patients were males. The average PSTR was 0.66 ± 0.12, the median dialysate mtDNA levels were 4325 copies/ul. The median concentrations of IL-6, IL-17A, TNF-α and IFN-γ were 25.9, 10.8, 25.8 and 17.9 pg/ml, respectively. We found that dialysate mtDNA was significantly correlated with PSTR (r = 0.461, P < 0.001), IL-6 (r = 0.568, P < 0.001), TNF-α (r = 0.454, P < 0.001) and IFN-γ (r = 0.203, P = 0.005). After adjustment for multiple covariates, dialysate mtDNA levels were independently correlated with IL-6 and PSTR. Dialysate mtDNA levels were not associated with patient survival.ConclusionsWe found that dialysate mtDNA levels correlated with the degree of intraperitoneal inflammatory status in PD patients. Peritoneal effluent mtDNA was an independent determinant of PSTR but did not affect patient survival.

Excessive salt intake increases peritoneal solute transport rate via local tonicity-responsive enhancer binding protein in subtotal nephrectomized mice.

High peritoneal transport is associated with high mortality and technical failure in peritoneal dialysis (PD). Baseline peritoneal solute transport rate (PSTR) as measured by the peritoneal equilibration test (PET) within 6 months after PD initiation varies between patients. Sodium is reported to be stored in the skin or muscle of dialysis patients. This study investigated whether excessive salt intake in uremic mice caused peritoneal alterations without exposure to PD fluid. Sham-operated (Sham) and subtotal nephrectomized (Nx) mice were randomly given tap water or 1% sodium chloride (NaCl)-containing water for 8 weeks. PET was then performed to evaluate peritoneal function. Human mesothelial cell line Met-5A was used for in vitro studies. We observed higher PSTR in Nx mice with 1% NaCl-containing drinking water (Nx + salt) compared with those with tap water (Nx + water), along with enhanced angiogenesis and inflammation in the peritoneum. Blockade of interleukin (IL)-6 signaling rescued peritoneal transport function in Nx + salt mice. In cultured Met-5A, additional NaCl in the medium upregulated IL-6 as well as vascular endothelial growth factor-A, associated with increased expression and nuclear translocation of tonicity-responsive enhancer binding protein (TonEBP). Knockdown of TonEBP lowered the induction caused by high tonicity. Peritoneal TonEBP expression was higher in Nx + salt mice, while removal of high-salt diet lowered TonEBP level and improved peritoneal transport function. Excessive dietary salt intake caused peritoneal membrane functional and structural changes under uremic status. TonEBP regulated hypertonicity-related inflammatory changes and might play a crucial role in high baseline peritoneal transport.

Peritoneal Protein Clearance Is a Function of Local Inflammation and Membrane Area Whereas Systemic Inflammation and Comorbidity Predict Survival of Incident Peritoneal Dialysis Patients.

It is not clear whether the association of increased peritoneal protein clearance (PPCl) with worse survival on peritoneal dialysis (PD) is a consequence of either local or systemic inflammation or indicative of generalized endothelial dysfunction associated with comorbidity. To investigate this we determined the relationship of PPCl to comorbidity, membrane area (equivalent to low molecular weight peritoneal solute transport rate), local and systemic inflammation and hypoalbuminaemia, and for each of these with patient survival. 257 incident patients from three GLOBAL Fluid Study centers were included in this analysis. Clinical profiles were collected at baseline along with a peritoneal equilibration test, 24-h dialysate protein and paired plasma and dialysate cytokine measurements. Although peritoneal protein clearance was associated with increased age and severe comorbidity on univariate analysis, only dialysate IL-6, peritoneal solute transport rate, plasma albumin and cardiac comorbidities (ischaemic heart disease and left ventricular dysfunction) were independent explanatory variables on multivariate analysis. While peritoneal protein clearance and daily peritoneal protein loss were associated with survival in univariate analysis, on multivariate analysis only plasma IL-6, age, residual kidney function, comorbidity, and plasma albumin were independent predictors. Peritoneal protein clearance is primarily a function of peritoneal membrane area and local membrane inflammation. The association with comorbidity and survival is predominantly explained by its inverse relationship to hypoalbuminaemia, especially in diabetics.

Associations Between Peritoneal Glucose Exposure, Glucose Degradation Product Exposure, and Peritoneal Membrane Transport Characteristics in Peritoneal Dialysis Patients: Secondary Analysis of the balANZ Trial.

Glucose is the most commonly used osmotic medium in peritoneal dialysis (PD) solutions, and its use has been associated with both local and systemic adverse effects. Previous, single-center, observational cohort studies have reported conflicting findings regarding whether a relationship exists between peritoneal glucose exposure and peritoneal small solute transport rate. In this secondary analysis of the balANZ multicenter, multinational, randomized controlled trial of a neutral pH, ultra-low glucose degradation product (biocompatible) versus conventional PD solutions over a 2-year period, the relationship between time varying peritoneal glucose exposure and change in peritoneal solute transport rate, (measured as dialysate to plasma creatinine ratio at 4 hours [D:PCr4h]), was evaluated using multivariable, multilevel linear regression. Baseline peritoneal glucose exposure was also assessed as either a continuous or categorical variable. The study included 165 patients (age 58.1 ± 14.2 years, 55% male, 33% diabetic). Peritoneal glucose exposure increased over time (coefficient 1.49, 95% confidence interval [CI] 1.07 - 1.92 and was not significantly associated with change in D:PCr4h (coefficient 0.00004, 95% CI -0.0001 - 0.0002, p = 0.68). Similar results were found when peritoneal glucose exposure was examined as a baseline continuous or categorical variable. A significant 2-way interaction was observed with PD solution type, whereby a progressive increase in D:PCr4h was seen in the patients receiving conventional PD solution, but not in those receiving biocompatible solution. Increases in peritoneal solute transport rate in PD patients over time were not associated with peritoneal glucose exposure, although a strong and positive association with PD solution glucose degradation product content was identified. Peritoneal glucose exposure may be a less important consideration than peritoneal glucose degradation product exposure with respect to peritoneal membrane function over time.

A Large Intraperitoneal Residual Volume Hampers Adequate Volumetric Assessment of Osmotic Conductance to Glucose

In end-stage renal disease patients treated with peritoneal dialysis (PD), the osmotic conductance to glucose (OCG) represents the intrinsic ability of the membrane to transport water in response to a crystalloid osmotic gradient. A progressive loss of OCG in long-term PD patients indicates the development of fibrosis in the peritoneal interstitium, and helps identify patients at risk for encapsulating peritoneal sclerosis. The double mini-peritoneal equilibration test (PET) has been proposed as a simple method to assess OCG using the difference in initial ultrafiltration rates generated by 2 successive dwells using 1.36% and 3.86% glucose-based, 1-h PET. However, the presence of a large peritoneal residual volume (RV) may potentially interfere with the correct evaluation of drained volumes, limiting the reliability of OCG assessed by the double mini-PET. We retrospectively reviewed data from 53 peritoneal function tests in 35 consecutive PD patients starting PD at our center between March 2013 and March 2017. The test consisted of a uni-PET (double mini-PET combined with a 3.86%, 4-h PET) performed at PD start, then yearly. In addition to peritoneal solute transport rate and net ultrafiltration, the tests provided information about osmotic water transport (OCG, sodium sieving, and free-water transport) as well as the RV estimated from albumin dilution. Contrary to sodium sieving, net ultrafiltration, and free-water transport, OCG did not correlate with any of the other parameters of osmotic water transport. In multivariate regression analyses, the RV was identified as the only determinant of OCG, while it did not alter the robust association between sodium sieving/free-water transport and their respective determinants. Considering only baseline tests or the whole series of tests, the presence of a large intraperitoneal RV was associated with discrepant values between OCG and sodium sieving, and with an artificial increase in OCG. A large RV leads to significant overestimation of OCG using the double mini-PET, potentially reducing the ability of OCG to identify patients with progressive fibrosis in the peritoneal interstitium. On the other hand, sieving of the dialysate sodium, a biochemical surrogate for OCG, is independent of the RV and may therefore be more reliable. A call for caution is warranted in patients with a large RV to avoid misinterpretation of OCG values derived from the double mini-PET.

Biocompatible Solutions and Long-Term Changes in Peritoneal Solute Transport.

The inflammation-driven increase in peritoneal solute transport rate that occurs during long-term peritoneal dialysis is associated with higher mortality, hospitalization, and encapsulating peritoneal sclerosis. Because biocompatible solutions were developed to mitigate these effects, we examined the association with their use and longitudinal peritoneal solute transport rate. We analyzed subjects from the multinational prospective Global Fluid Study with three or more peritoneal solute transport rate measurements >2 months from the start of peritoneal dialysis. Follow-up was for 7.5 years (median, 2.3 years; interquartile range, 1.8-3.6) in biocompatible solutions and 12.8 years (median, 3.2 years; interquartile range, 1.9-4.3) for standard solutions. Using a random intercept/slopes multilevel model, we examined the association of patients using biocompatible solutions and peritoneal solute transport rate over time, adjusting for center effects, dialysate dextrose concentration, baseline dialysate IL-6 concentration, icodextrin use, residual kidney function, and peritonitis. Of 366 patients, the 71 receiving biocompatible solutions throughout their time on peritoneal dialysis had a mean adjusted dialysate-to-plasma creatinine ratio of 0.67 compared with 0.72 for standard solutions (P=0.02). With duration of treatment, there was a continuous increase in peritoneal solute transport rate in patients using standard solutions (range, 2 months to 4 years). In contrast, patients using biocompatible solutions had peritoneal solute transport rates that plateaued after 2 years of therapy. These changes in peritoneal solute transport rate were independent of baseline inflammation and time-varying predictors of faster peritoneal solute transport rate. In patients suffering episodes of peritonitis while using standard solutions, there was an associated increase in peritoneal solute transport rate of 0.020 (95% confidence interval, 0.01 to 0.03) per episode, whereas in patients using biocompatible solutions, there was no change in this parameter (-0.014; 95% confidence interval, -0.03 to <0.01). These data suggest that a different temporal pattern in changes in peritoneal solute transport rate occurs during the course of peritoneal dialysis according to solution type and that patients using biocompatible solutions may avoid the increase in solute transport associated with peritonitis.

Differences in peritoneal solute transport rates in peritoneal dialysis.

Ultrafiltration failure associated with peritoneal membrane dysfunction is one of the main complications for patients on long-term peritoneal dialysis (PD). The dialysate-to-plasma concentration ratio (D/P) of creatinine is widely used to assess peritoneal membrane function. However, other small-sized solutes have not been studied in detail as potential indicators of peritoneal permeability. We studied the D/Ps of small, middle-sized and large molecules in peritoneal equilibration tests in 50 PD patients. We applied metabolomic analysis of comprehensive small molecular metabolites using capillary electrophoresis time-of-flight mass spectrometry. D/Ps of middle-sized and large molecules correlated positively with D/P creatinine. Most D/Ps of small molecules correlated positively with D/P creatinine. Among 38 small molecules contained in the dialysate, urea, citrulline and choline showed significantly lower ability to permeate than creatinine. In the relationship between D/Ps of creatinine and small molecules, regression coefficients of three molecules were less than 0.3, representing no correlation to D/P creatinine. Five molecules showed negative regression coefficients. Among these molecules, hippurate and 3-indoxyl sulfate showed relatively high teinpro binding rates, which may affect permeability. Serum concentrations of two molecules were higher in the Low Kt/V group, mainly due to high protein binding rates. D/Ps of some molecules did not correlate with D/P creatinine. Factors other than molecular weight, such as charge and protein binding rate, are involved in peritoneal transport rates. Metabolomic analysis appears useful to analyze small molecular uremic toxins, which could accumulate in PD patients, and the status of peritoneal membrane transport for each molecule.