Peritoneal Equilibration Test Research Articles

Supine equilibration of extracellular fluid in peritoneal dialysis varies with intra-abdominal pressure.

Increased intra-abdominal pressure (PIA) leads to venous congestion in splanchnic and adjoining circulations. The aim is to examine whether PIA in peritoneal dialysis (PD) affects the mobilization of extracellular fluid from the lower body in supine body position. Patients were studied during a regular peritoneal equilibration test (PET) in supine body position using multifrequency bioimpedance analysis to determine extracellular resistance and absolute volume overload (AVO) in wrist-to-ankle (W2A) as well as in ankle-to-ankle (A2A) configurations. Measurements were taken at baseline (T0) after draining the peritoneal cavity, at T1 shortly after filling with 2 L of standard dialysate, and at T2 before taking the 2 h PET samples. PIA was measured from the column height in the PD catheter. Extracellular resistance in the lower extremities (RL) was taken as half of the A2A resistance. Eighteen patients (56 ± 15 years, 76 ± 21 kg, body mass index (BMI) 26.4 ± 7 kg/m2, 13 men) were studied. After having assumed a supine body position for the duration of 17, 77, and 155 min, AVO continuously decreased from 1.6 ± 1.3 (T0) to 1.2 ± 1.5 (T1) and 1.0 ± 1.4 L (T2). RL significantly increased from 238 ± 57 (T0) to 254 ± 62 (T1) and 264 ± 67 Ohm (T2). This increase was negatively correlated to BMI and PIA measured at any time point, but not to net ultrafiltration volume. Orthostatic fluid shifts from the lower limbs may take up to 2 h in supine PD patients, especially with high BMI and PIA because of venous congestion in splanchnic and adjoining circulations.

Randomized controlled trial to compare the tolerability and efficacy of treatment with Icodextrin 7.5% versus Dextrose 2.5% in chronic peritoneal dialysis patients with high/high average solute transport characteristics and low residual renal function

Aim: Comparison of tolerability and efficacy of treatment with icodextrin vs. dextrose 2.5% amongst high risk cohort of chronic peritoneal dialysis patients (high/high average solute transport characteristics and low residual renal function) over 3 months. Study Design and Methodology: The study was an open-label, comparative, prospective, randomized controlled trial, conducted at department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India. A total of 349 end stage renal disease patients on chronic peritoneal dialysis were screened for eligibility over a period of 6 months and 41 patients with high / high average solute transport characteristics and low residual renal function were randomized to receive either icodextrin 7.5% solution or 2.5% dextrose solution in long dwell. Patients were assessed for adequacy of peritoneal dialysis (creatinine & urea clearance), peritoneal membrane transport characteristics including solute clearance (standard peritoneal equilibration test), body composition, total body water, fat mass and fat free mass (using whole body tetrapolar bioimpedance analyzer) at baseline and at the end of 3 months. Statistical Analysis: Continuous variables were compared with independent samples paired t test if normally distributed, or with Mann–Whitney U test if the distribution was skewed. Categorical variables were analyzed with Chi-square test or Fisher exact test as appropriate. Pearson's correlation coefficient was calculated between different quantitative variables. Paired t test and Wilcoxon signed-rank test were used for within-group comparisons. Repeated measure ANOVA was used to compare bioelectrical impedance between intervention groups. Results: The study has shown that use of icodextrin based continuous ambulatory peritoneal dialysis resulted in better ultrafiltration and improved solute clearance when compared to 2.5% dextrose based peritoneal dialysis in a select cohort of patients having high/high average transporter characteristics with poor residual renal function, however, it didn't significantly alter total body water and failed to translate into improvements in either patient's or physician's assessment of global health of response to therapy atleast at 3 months. Conclusions: Although use of icodextrin based peritoneal dialysis solution for long dwell resulted in significant improvement in solute clearance and ultrafiltration nevertheless failed to translate into better hydration status or subjective improvement scores atleast at 3 months.

Peritoneal dialysis induces alterations in the transcriptome of peritoneal cells before detectible peritoneal functional changes.

Long-term peritoneal dialysis (PD) is associated with functional and structural alterations of the peritoneal membrane. Inflammation may be the key moment, and, consequently, fibrosis may be the end result of chronic inflammatory reaction. The objective of the present study was to identify genes involved in peritoneal alterations during PD by comparing the transcriptome of peritoneal cells in patients with short- and long-term PD. Peritoneal effluent of the long dwell of patients with stable PD was centrifuged to obtain peritoneal cells. The gene expression profiles of peritoneal cells using microarray between patients with short- and long-term PD were compared. Based on microarray analysis, 31 genes for quantitative RT-PCR validation were chosen. A 4-h peritoneal equilibration test was performed on the day after the long dwell. Transport parameters and protein appearance rates were assessed. Genes involved in the immune system process, immune response, cell activation, and leukocyte and lymphocyte activation were found to be substantially upregulated in the long-term group. Quantitative RT-PCR validation showed higher expression of CD24, lymphocyte antigen 9 (LY9), TNF factor receptor superfamily member 4 (TNFRSF4), Ig associated-α (CD79A), chemokine (C-C motif) receptor 7 (CCR7), carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), and IL-2 receptor-α (IL2RA) in patients with long-term PD, with CD24 having the best discrimination ability between short- and long-term treatment. A relationship between CD24 expression and genes for collagen and matrix formation was shown. Activation of CD24 provoked by pseudohypoxia due to extremely high glucose concentrations in dialysis solutions might play the key role in the development of peritoneal membrane alterations.

Curcumin ameliorates peritoneal fibrosis via inhibition of transforming growth factor-activated kinase 1 (TAK1) pathway in a rat model of peritoneal dialysis

BackgroundPeritoneal fibrosis (PF) remains a serious complication of long-term peritoneal dialysis (PD). The goal of this study was to investigate the anti-fibrotic effects of curcumin on the PF response to PD and its’ mechanism.MethodsMale Sprague–Dawley rats were infused with 20 mL of 4.25% glucose-based standard PD fluid for 8 consecutive weeks to establish PF model and then divided into five groups: Control, received sham operation and 0.9% physiological saline; PD, received 4.25% standard PD fluid; Curcumin, PD rats injected intraperitoeally with curcumin for 8 weeks at doses of 10, 20 or 40 mg/kg. Masson’s staining was performed to evaluate the extent of PF. Peritoneal Equilibration Test (PET) was conducted to assess ultrafiltration volume (UFV) and mass transfer of glucose (MTG), quantitative RT-PCR, and immunohistochemistry or western blotting were performed to measure the expression levels of inflammation and fibrosis-associated factors. We also detected the TGF-β1 in peritoneal fluid by ELISA.ResultsCompared with the control group, the PD rats showed decreased UFV (2.54 ± 0.48 to 9.87 ± 0.78 mL, p < 0.05] and increased MTG (18.99 ± 0.86 to 10.85 ± 0.65 mmol/kg, p < 0.05) as well as obvious fibroproliferative response, with markedly increased peritoneal thickness (178.33 ± 4.42 to 25.26 ± 0.32um, p < 0.05) and higher expression of a-SMA, collagen I and TGF-β1. Treatment with curcumin significantly increased UFV, reduced MTG and peritoneal thickness of PD rats. The elevated TGF-β1 in peritoneal fluid of PD rats was significantly decreased by curcumin. It attenuated the increase in protein and mRNA of TGF-β1, α-SMA and collagen I in peritoneum of PD rats. The mRNA expressions of TAK1, JNK and p38, as well as the protein expressions of p-TAK1, p-JNK and p-p38 in peritoneum of PD rats were reduced by curcumin.ConclusionsPresent results demonstrate that curcumin showed a protective effect on PD-related PF and suggest an implication of TAK1, p38 and JNK pathway in mediating the benefical effects of curcumin.

Proteomic profiling of peritoneal dialysis effluent-derived extracellular vesicles: a longitudinal study.

Peritoneal dialysis (PD) is an optimal renal replacement therapy for patients while waiting for kidney transplantation, but functional failure of the peritoneal membrane (PM), mainly induced by exposure to PD solutions, force many patients to early abandon PD therapy. PM function is evaluated by the peritoneal equilibration test (PET), a tedious technique only detecting alterations in extensively damaged PM. In a previous study, we showed that peritoneal dialysis effluent contained extracellular vesicles (PDE-EV), and that their proteome was significantly different between newly enrolled and long-term PD patients. Here, we report the results of a longitudinal study and compare PDE-EV proteome changes with PET results. PDE was collected from 11 patients every 6months (coincident with PET controls) from 0months up to 24months on PD. PDE-EV were isolated by size-exclusion chromatography and the proteome was analyzed by mass spectrometry (LC-MS/MS). Bioinformatic analyses were conducted to evaluate differences between groups. At follow-up endpoint, patients were classified as Stable (n = 7) or Unstable (n = 4) according to PET evolution. Strikingly, PDE-EV from the Stable group showed a significantly higher protein expression compared to Unstable patients already at 6months on PD, when PET alterations had not been detected yet. PDE-EV proteome show alterations much earlier than PET monitoring, thus unveiling the potential of PDE-EV proteins as feasible biomarkers of PM alteration in PD patients.

The Behavior of the Type of Peritoneal Transport in the Inflammatory and Oxidative Status in Adults Under Peritoneal Dialysis.

Peritoneal dialysis (PD) is an alternative for managing the end-stage renal disease (ESRD). The peritoneal membrane (PM) is not just a membrane that passively responds to diffusion and convection. The characteristics of PM result in the peritoneal equilibrium test (PET) and with this test is possible to obtain the type of peritoneal transport (PT). The patient on PD can be classified in different types of PT as; Low, Low Average, High Average, and High. The aim of the study was to compare the inflammatory cytokines, oxidants, antioxidants, and oxidative DNA damage markers in the different types of PT. A cross-sectional analytical study of 77 adult PD patients was performed. Levels of lipoperoxides (LPO) were higher in all types of PT vs. healthy volunteer controls (HC) (p < 0.0001). Nitric oxide (NO) levels were found significantly down-regulated in all types of PT (p < 0.0001). The activity of the superoxide dismutase enzyme (SOD) was found to be significantly increased in all types of PT vs. the HC (p < 0.0001). The levels of the DNA repair enzyme were found to be decreased in all types of PT. The levels of the pro-inflammatory cytokines TNF-α, IL-6, the marker of oxidative DNA damage, 8-IP and the total antioxidant capacity (TAC) were all significantly decreased, contrary to the levels in HC, possibly by the clearance in the dialysis fluid in all types of PT or due to down-regulation of their expression. In conclusion, we found significant changes in markers of inflammation, oxidative stress, and oxidative damage to DNA in all types of PT; Low, low average, high average, and high PT in the values of D/P creatinine at 4 h compared to HC.

Unraveling Hepcidin Plasma Protein Binding: Evidence from Peritoneal Equilibration Testing.

Peptide hormone hepcidin regulates systemic iron metabolism and has been described to be partially bound to α2-macroglobulin and albumin in blood. However, the reported degree of hepcidin protein binding varies between <3% and ≈89%. Since protein-binding may influence hormone function and quantification, better insight into the degree of hepcidin protein binding is essential to fully understand the biological behavior of hepcidin and interpretation of its measurement in patients. Here, we used peritoneal dialysis to assess human hepcidin protein binding in a functional human setting for the first time. We measured freely circulating solutes in blood and peritoneal fluid of 14 patients with end-stage renal disease undergoing a peritoneal equilibration test to establish a curve describing the relation between molecular weight and peritoneal clearance. Calculated binding percentages of total cortisol and testosterone confirmed our model. The protein-bound fraction of hepcidin was calculated to be 40% (±23%). We, therefore, conclude that a substantial proportion of hepcidin is freely circulating. Although a large inter-individual variation in hepcidin clearance, besides patient-specific peritoneal transport characteristics, may have affected the accuracy of the determined binding percentage, we describe an important step towards unraveling human hepcidin plasma protein binding in vivo including the caveats that need further research.

Dialysis monitoring: peritoneal equilibrium test, regional citrate anticoagulation and residual renal function

The SFBC working group aimed to deal with biological tests outside the French nomenclature that may be useful for the follow-up of dialysis patients. Our discussion was divided into 3 parts: 1) evaluation of peritoneal membrane characteristics; 2) monitoring of renal replacement therapy using regional citrate anticoagulation; 3) estimation of residual renal function (RRF). International recommendations underline the importance of assessing peritoneal membrane characteristics for peritoneal dialysis prescription. This peritoneal equilibrium test requires the measurement in dialysate of the following parameters: glucose, urea, creatinine and sodium. As part of the monitoring of continuous renal replacement therapy using regional citrate anticoagulation, the determination of ionized calcium assay is essential according to national and international guidelines to ensure a balance between effective anticoagulation and appropriate calcium levels. Finally, the RRF plays a key role in the dialysis adequacy and patient survival. European and international recommendations highlight the potential interest of RRF in peritoneal dialysis and hemodialysis. The RRF corresponds to the mean of urinary urea and creatinine clearance, assessed from a urine collection with measurement of urinary urea.

Comparison of the current status of peritoneal dialysis between Foshan and other relatively developed countries or areas

Objective To investigate the current status of peritoneal dialysis (PD)patients in the hospital and to improve the treatment and management of PD. Methods Data of 178 patients undergoing PD were retrospectively analyzed, who underwent dialysis more than three months in five years and then compared with those from other relatively developed countries or areas. Results Compared with other relatively developed countries or areas, the PD patients were younger, the average age was 50.1 years, and the male patients accounted for 48.9%, the female patients accounted for 51.1%.The primary disease was chronic nephritis(54.5%), the incidence of peritonitis was lower(1 person/56 months), the pathogenic bacteria was mainly Gram-positive bacteria, accounting for 40.9%.There were 94 cases of erythroprotein less than 110 g/L(52.8%), 37 cases of serum protein less than 35 g/L(21%), 92 cases of calcium and phosphorus metabolism abnormality(51.5%), and 59.7% PD patients were KT/V>2.0 mmol/L, and peritoneal equilibration test(PET) showed high average transhipment accounted for 49.4%. Conclusions The patients with PD in our center are significantly different from those in developed countries or regions. Key words: Peritoneal Dialysis; GUANGDONG

Correlation between Ultrafiltration Coefficient and Effective Lymphatic Absorption Rate in Continuous Ambulatory Peritoneal Dialysis Patients: A Possible Paradigm Shift.

Background:The relative contribution of transcapillary water movement and lymphatic reabsorption in peritoneal dialysis (PD) is a critical issue, particularly in patients with ultrafiltration failure (UFF). Based on routine results obtained from the PD Adequest 2.0 software, the present study aimed to re-evaluate the separate effects of transcapillary water movement and lymphatic reabsorption on the net ultrafiltration capacity in continuous ambulatory peritoneal dialysis (CAPD) patients without UFF. Methods:Seventy CAPD patients without UFF and PD duration less than 2 years entered the study. The study was conducted during January-April 2016 at Mashhad University of Medical Sciences, Mashhad, Iran. Each patient had 1 to 3 peritoneal equilibration test (PET) results which were used to analyze the determinants of fluid transport, lymphatic reabsorption, and ultrafiltration. Pearson and Spearman correlation tests were used to determine the correlation between continuous and ordinal factors, respectively. The data were analyzed using the SPSS software version 19.0. Results:In terms of the effective lymphatic absorption rate (ELAR) and ultrafiltration coefficient (LpA) values, there was no difference in the high or high-average transporters compared to the low or low-average transporters. However, a positive and highly significant correlation between ELAR and LpA was found. Conclusion: A significant correlation between ELAR and LpA was found in CAPD patients without UFF and duration less than 2 years from the beginning of PD. The abstract was presented in the 53rd ERA-EDTA Congress, Austria, as a poster and published in Nephrology Dialysis Transplantation as a supplement (2016; Vol. 31).

MON-072 FAST PERITONEAL MEMBRANE PERMEABILITY WAS NOT ASSOCIATED WITH MORTALITY IN PATIENTS ON PERITONEAL DIALYSIS

Peritoneal dialysis (PD) patients have different peritoneal membrane transport characteristics. In this study, we aimed to investigate the relationship between the peritoneal membrane transport and mortality in incident PD patients. The study included 231 PD patients. A standardized peritoneal equilibration test (PET) test was performed on all patients, 4-6 weeks after initiation of regular PD. The patients were divided two groups according to PET result: fast group (fast and fast-average) and slow group (slow-average and slow). The mean patient age was 50.4±14.1 years. Fast group included more male patients (70% vs 56.4%, p=0.038). Fast group had a lower peritoneal Kt/V (1.67±0.37 vs 1.84±0.45, p=0.02) and ultrafiltration (744±627 vs 1050±703, p=0.012), compared to slow group. However, the survival of the PD patients was comparable between the two groups (log-rank P=0.481). Cox-multivariate analysis revealed only age (RR=1.075, p < 0.001), and diabetes (RR = 2.958, p = 0.001) to be independent predictors of mortality. In our study, initial fast peritoneal membrane permeability was not associated with mortality in PD patients.

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.

Clearance of Magnesium in Peritoneal Dialysis Patients: A Single-Center Study

Objective: This retrospective study aimed to investigate the clearance of magnesium (Mg) in peritoneal dialysis (PD) patients and its influencing factors. Methods: The demographic information, clinical characteristics and laboratory data of the patients were collected. According to the corrected serum Mg (cS-Mg) concentration, patients were divided into 3 groups including hypomagnesemia (Mg²⁺ < 0.77 mmol/L, group A), normal serum Mg concentration (0.77 mmol/L ≤ Mg²⁺ ≤1.03 mmol/L, group B), and hypermagnesemia (Mg²⁺ > 1.03 mmo/L, group C). Results: One hundred and fifteen patients were enrolled, and their mean 24 h-peritoneal Mg clearance was 39.75 ± 17.42 mg. The mean normalized peritoneal Mg clearance rate was 1.82 ± 0.82 L/day/1.73 m². Twenty-four-hour peritoneal Mg clearance of group A was significantly lower than that of group C (p < 0.05). Bivariate correlation analysis showed that cS-Mg was positively correlated with peritoneal dialysate Mg concentration (p < 0.01). cS-Mg was negatively correlated with the normalized peritoneal Mg clearance rate (p < 0.05). The normalized peritoneal Mg clearance rate was positively correlated with prealbumin (p < 0.05), daily peritoneal protein loss (p < 0.01) and the normalized PD-creatinine clearance rate (p < 0.01). The normalized peritoneal Mg clearance rate was also negatively correlated with the normalized renal-creatinine clearance rate (p < 0.01). Furthermore, cS-Mg of patients with continuous ambulatory PD (CAPD) was significantly lower than that of patients with daytime ambulatory PD (DAPD, p < 0.01). The normalized peritoneal Mg clearance rate of patients with CAPD was significantly higher than that of patients with DAPD (p < 0.01). Moreover, among the patients with different peritoneal transport characteristics of peritoneal equilibration test, the normalized peritoneal Mg clearance rate of high average transport patients was significantly higher than that in those with low transport, low average transport and high transport (p < 0.05). Conclusions: Serum Mg could be partly cleared by PD. The peritoneal Mg clearance was positively related with serum Mg concentration, which was concentration-dependent. Peritoneal Mg clearance was negatively correlated with the residual renal function, while being positively correlated with the nutritional status and daily peritoneal protein loss. Peritoneal Mg clearance was higher in patients with high transport characteristics or CAPD.

Targeted Metabolomic Profiling of Peritoneal Dialysis Effluents Shows Anti-oxidative Capacity of Alanyl-Glutamine.

Readily available peritoneal dialysis (PD) effluents from PD patients in the course of renal replacement therapy are a potentially rich source for molecular markers for predicting clinical outcome, monitoring the therapy, and therapeutic interventions. The complex clinical phenotype of PD patients might be reflected in the PD effluent metabolome. Metabolomic analysis of PD effluent might allow quantitative detection and assessment of candidate PD biomarkers for prognostication and therapeutic monitoring. We therefore subjected peritoneal equilibration test effluents from 20 stable PD patients, obtained in a randomized controlled trial (RCT) to evaluate cytoprotective effects of standard PD solution (3.86% glucose) supplemented with 8 mM alanyl-glutamine (AlaGln) to targeted metabolomics analysis. One hundred eighty eight pre-defined metabolites, including free amino acids, acylcarnitines, and glycerophospholipids, as well as custom metabolic indicators calculated from these metabolites were surveyed in a high-throughput assay requiring only 10 μl of PD effluent. Metabolite profiles of effluents from the cross-over trial were analyzed with respect to AlaGln status and clinical parameters such as duration of PD therapy and history of previous episodes of peritonitis. This targeted approach detected and quantified 184 small molecules in PD effluent, a larger number of detected metabolites than in all previous metabolomic studies in PD effluent combined. Metabolites were clustered within substance classes regarding concentrations after a 4-h dwell. PD effluent metabolic profiles were differentiated according to PD patient sub-populations, revealing novel changes in small molecule abundance during PD therapy. AlaGln supplementation of PD fluid altered levels of specific metabolites, including increases in alanine and glutamine but not glutamate, and reduced levels of small molecule indicators of oxidative stress, such as methionine sulfoxide. Our study represents the first application of targeted metabolomics to PD effluents. The observed metabolomic changes in PD effluent associated with AlaGln-supplementation during therapy suggested an anti-oxidant effect, and were consistent with the restoration of important stress and immune processes previously noted in the RCT. High-throughput detection of PD effluent metabolomic signatures and their alterations by therapeutic interventions offers new opportunities for metabolome-clinical correlation in PD and for prescription of personalized PD therapy.

Monitoring of Intraperitoneal Fluid Volume during Peritoneal Equilibration Testing using Segmental Bioimpedance

Background: Ultrafiltration failure and fluid overload are common in peritoneal dialysis (PD) patients. Knowledge of intraperitoneal volume (IPV) and time to peak IPV during a dwell would permit improved PD prescription. This study aimed to utilize trunk segmental bioimpedance analysis (SBIA) to quasi-continuously monitor IPV (IPV_SBIA) during the peritoneal dwell. Methods: IPV_SBIA was measured every minute using lower-trunk SBIA (Hydra 4200; Xitron Technologies Inc., CA, USA) in 10 PD patients during a standard 240-min peritoneal equilibration test (PET). The known dialysate volume (2 L) rendered IPV_SBIA calibration and calculation of instantaneous ultrafiltration volume (UFV_SBIA) possible. UFV_SBIA was defined as IPV_SBIA – 2 L. Results: Based on dialysate-to-plasma creatinine ratio, 2 patients were high, 7 high-average, and 1 low-average transporters. Technically sound IPV_SBIA measurements were obtained in 9 patients (age 59.0 ± 8.8 years, 7 females, 5 African Americans). Drained ultrafiltration volume (UFV_drain) was 0.47 ± 0.21 L and correlated (r = 0.74; p < 0.05) with end-dwell UFV_SBIA (0.55 ± 0.17 L). Peak UFV_SBIA was 1.04 ± 0.32 L, it was reached 177 ± 61 min into the dwell and exceeded end-dwell UFV_SBIA by 0.49 ± 0.28 L (95% CI: 0.27–0.7) and UFV_drain by 0.52 ± 0.31 L (95% CI: 0.29–0.76), respectively. Conclusion: This pilot study demonstrates the feasibility of trunk segmental bioimpedance to quasi-continuously monitor IPV_SBIA and identify the time to peak UFV_SBIA during a standard PET. Such new insights into the dynamics of intraperitoneal fluid volume during the dwell may advance our understanding of the underlying transport physiology and eventually assist in improving PD treatment prescriptions.

The relationship between vascular endothelial growth factor (VEGF) in the serum and drained dialysate with the quality of peritoneal dialysis and peritoneal membrane transport rates

Vascular endothelial growth factor (VEGF), a powerful angiogenetic agent crucial for microvascular hyperpermeability and neoangiogenesis in the peritoneum, is associated with increased solute transport rates in chronic peritoneal dialysis (PD) patients. We investigated the correlation between serum and drained dialysate (dd) concentrations of VEGF and the transport characteristics of peritoneal membrane and dialysis quality in 20 patients with end-stage renal failure at the beginning and after six months of PD. The serum VEGF (sVEGF) concentration rose significantly (149.33?}116.71 pg/ mL vs 239.36?}102.23 pg/mL; p=0.012) and ddVEGF concentration increased slightly (38.44?}50.47 pg/mL vs 43.55?}51.10 pg/mL) during the first 6 months of PD. At the beginning of chronic PD, ddVEGF concentrations correlated inversely with the peritoneal equilibrium test (PET) glucose (R=-0.565; p=0.009) and creatinine (R=-0.506; p=0.023) and residual renal function (RRF) (R=-0.691; p=0.001); sVEGF concentrations inversely correlated with PET creatinine (R=-0.457; p=0.043) and residual diuresis (RD) (R=-0.691; p=0.001). After 6 months of treatment, ddVEGF concentrations correlated directly with PETcreatinine (R=0.450; p=0.047), and inversely with RRF (R=-0.552; p=0.012) and residual renal weekly Kt/V (R=-0.488; p=0.029). The sVEGF concentration inversely correlated with RD (R=-0.589; p=0.006). High ddVEGF at the beginning of PD is predictive of adverse alterations of the peritoneal membrane, i.e. increased transport rate of glucose and creatinine. ddVEGF values may help to identify patients who will preserve adequate transport characteristics of the peritoneal membrane and maintain successful long-term PD.

A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health

In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and exvivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and exvivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased exvivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.