Peritoneal Transport Characteristics Research Articles

Peritoneal Protein Transport during the Baseline Peritoneal Equilibration Test Is an Accurate Predictor of the Outcome of Peritoneal Dialysis Patients

Background: Peritoneal protein excretion (PPE) is a potential marker of the outcome in peritoneal dialysis (PD) patients. Method: Observational study of a cohort of 269 patients starting PD in a single unit. Study variables: total PPE during a baseline peritoneal equilibration test (PET; PET-PPE) and 24-hour PPE. Control variables: essential baseline demographic, laboratory and adequacy markers. Main outcomes: mortality, cardiovascular events and risk of peritonitis. We applied univariate and multivariate strategies of survival analysis. Main Results: PET-PPE sustained a significant, yet limited correlation with 24-hour PPE (r = 0.46, p < 0.0005). At baseline, the main study variables showed an independent correlation with peritoneal transport characteristics (D/P_240’ creatinine) and cardiovascular comorbidity. PET-PPE (p < 0.0005, model global χ² 59.4) was a more accurate predictor of overall mortality than 24-hour PPE (p = 0.04, χ² 50.5). Moreover, PPE during PET, but not 24-hour PPE, was an independent predictor of the risks of cardiovascular and infectious mortality, and of peritonitis. Conclusions: Baseline PPE represents a strong independent marker of survival of PD patients. Estimation of PPE during PET is more accurate than 24-hour PPE for this purpose, sustains a definite independent association with cardiovascular and infectious mortality, and shows a significant correlation with the risk of peritonitis.

Risk factors for mortality in diabetic peritoneal dialysis patients

It is well established that the survival rate of diabetic end-stage renal disease patients remains the lowest among all primary diagnoses probably because of higher prevalence of cardiovascular diseases (CVD) associated with diabetes. This study was designed to evaluate the impact of CVD and other risk factors individually or in combination on mortality in diabetic peritoneal dialysis (PD) patients. In a retrospective study, 213 incident PD patients [118 had diabetes mellitus (DM), 94 were female, mean age 55 ± 13 years] underwent initial assessment of nutritional status, comorbid disease (CMD) survey, residual renal function (RRF), dialysis adequacy and peritoneal transport characteristics at a mean of 9 days (range, 3-24 days) after start of PD and were then followed for 30 ± 24 months (range, 3-115 months). Of 213 patients, 154 patients were reassessed after a mean of 11 months (range, 6-19 months). Nutritional status was assessed by subjective global assessment and other methods. CMD was graded by Davies index and included DM, CVD, liver disease and respiratory disease. On Kaplan-Meier analysis, patient survival was significantly lower in female DM patients compared to other groups. The 3-year patient survival rate was 46, 70, 82 and 83% for female DM, male DM, male non-DM and female non-DM, respectively (P = 0.003). On Cox proportional hazards multivariate analysis including all patients, old age, presence of CVD or protein-energy wasting (PEW), low serum albumin concentration and low RRF were independent predictors of mortality but not DM per se or female gender. In DM patients, old age, female gender, presence of CVD or PEW and low RRF were independent predictors of mortality while old age was the only risk factor in non-DM patients. After adjustment for age, gender and RRF, DM patients with both CVD and PEW had a risk of mortality that was 3.3 times that of DM patients without CVD and PEW. In DM patients without CVD and PEW, patient survival was not different from that of non-DM patients without CVD and PEW. DM per se was not a risk factor for mortality in this group of PD patients. Instead, the higher mortality rate in diabetic PD patients, in particular among female patients, was mainly attributable to concurrent morbidity such as CVD and PEW, together with low RRF.

Factors associated with increased pulse wave velocity in peritoneal dialysis patients

Abstract Elevated pulse wave velocity (PWV) reflects increased arterial stiffness. Several studies have investigated PWV in peritoneal dialysis (PD) patients, but direct comparisons with healthy controls were not done. The potential influence of peritoneal transport characteristics on arterial stiffness in PD patients was suggested in recent studies. The aims of this study were to compare PWV in PD patients and healthy volunteers, and to investigate factors associated with increased PWV. The carotid-femoral PWV was measured in 28 PD patients and 28 healthy controls, matched for age and gender. A peritoneal equilibration test (PET) was performed in all PD patients. Based on the PET, patients were classified as: high transporters (H) (n=8), high-average (HA) (n=12), low-average (LA) (n=6), and low transporters (L) (n=2). Six of the PD patients were diabetic. PWV was significantly higher in the PD patients than in the controls (9,9±2,4 vs. 8,0±0,9; p=0,0004). In the PD group, PWV was higher in H/HA than in L/LA patients (10,4 ± 2,5 vs. 8,6 ± 1,0; p=0,008), but all the diabetic patients were in the H/HA group. PWV was significantly higher in diabetic than in non-diabetic PD patients (12,8 ± 2,0 vs. 9,1 ± 1,7; p=0,004). In the PD patients, significant positive correlations were found between PWV and: age, pulse pressure, Kt/V, and duration of PD therapy. In conclusion, the carotid-femoral PWV is elevated in peritoneal dialysis patients. Increased PWV in PD patients is associated with age, diabetic status, and longer duration of PD therapy, but not with this type of peritoneal transport.

BMP-7 stops TGF- in peritoneal fibrosis

In this issue, Loureiro, and Cabrera et al. study the regulation of transforming growth factor beta-1 (TGF-β) signalling by bone morphogenetic protein-7 (BMP-7) in the biology of peritoneal dialysis-related peritoneal fibrosis. Peritoneal dialysis (PD) is a highly effective and convenient mode of renal replacement therapy, the success of which depends on the structural and functional integrity of the peritoneal membrane. Progressive alterations in peritoneal membrane transport characteristics commonly cause technique failure in PD, and are associated with fibroproliferative changes in the peritoneal membrane, including vasculopathy, accumulation of submesothelial extracellular matrix, and denudation and altered appearance of mesothelial cells [1]. The fundamental causes of these changes are likely to be long-term exposure to bioincompatible dialysate, together with recurrent episodes of bacterial peritonitis. Fibroproliferative diseases are largely driven by fibroblasts, spindle-shaped, motile, contractile cells that respond to pro-fibrotic stimuli by synthesizing and organizing extracellular matrix. Fibroblasts may originate from proliferation of local tissue fibroblasts, from circulating bone marrow-derived precursors (fibrocytes) and from resident epithelial cells by epithelial-to-mesenchymal transition (EMT) [2]. During EMT, epithelial cells lose intercellular adhesiveness and apical–basal polarity, and acquire a motile and contractile phenotype [3]. High-glucose concentrations typical of peritoneal dialysate induce such phenotypic change in mesothelial cells in vitro [4]. Additionally, the previous work of Cabrera et al. demonstrated progressive loss of epithelial morphology in mesothelial cells

Arterial Pulse Wave Velocity and Peritoneal Transport Characteristics Independently Predict Hospitalization in Chinese Peritoneal Dialysis Patients

Cardiovascular disease (CVD) is the most common cause of mortality in chronic peritoneal dialysis (PD) patients. Increased arterial stiffness may be related to a high peritoneal permeability resulting in fluid overload in PD patients. We studied the relations between arterial stiffness, peritoneal transport, and radiographic parameters of systemic fluid overload in a cohort of Chinese PD patients. Prospective cohort study. University referral center. We studied 107 PD patients. Vascular pedicle width and cardiothoracic ratio were measured from a plain postero-anterior chest radiograph. Pulse wave velocity (PWV) was determined at carotid-femoral (C-F) and carotid-radial sites. Peritoneal transport was determined by the dialysate-to-plasma ratio (D/P) of creatinine at 4 hours of dwell. Patients were followed for 9.4 +/- 4.6 months. Duration of hospitalization; actuarial and technique survival. There were no relationships between radiographic measures, arterial PWV, and D/P creatinine. However, both C-F PWV and D/P creatinine were independent predictors of the number of hospitalizations for CVD. None of the parameters correlated with mortality in this study. There were no relationships between radiological parameters of fluid overload, peritoneal transport characteristics, and arterial PWV. Both C-F PWV and D/P creatinine were independent predictors of the number of hospitalizations for CVD. Our result suggests that arterial stiffness and high peritoneal transport each contribute to the development of CVD in this group of patients.

Phosphate Elimination in Modalities of Hemodialysis and Peritoneal Dialysis

Hyperphosphatemia is highly prevalent in hemodialysis (HD) and peritoneal dialysis (PD) patients and is a major risk factor for cardiovascular mortality. Elimination of inorganic phosphate by dialysis is a cornerstone of the management of hyperphosphatemia. Phosphate clearance during HD is affected by various factors of dialysis prescription, such as blood and dialysate flow rate, dialyzer membrane surface area and ultrafiltration volume. Phosphate mass removal can be improved by hemodiafiltration, increased dialysis frequencies and extended treatment times. Short daily or extended daily or 3 times weekly nocturnal HD allow higher phosphate mass removal and potentially complete discontinuation of phosphate binder medication. In PD, phosphate mass removal appears to be correlated with peritoneal creatinine but not urea clearance. In hyperphosphatemic PD patients, the decision on the optimal PD modality should be based on peritoneal creatinine and ideally also on peritoneal phosphate transport characteristics.

Endothelial Dysfunction in Peritoneal Dialysis Patients With and Without Failed Renal Transplants

Background Endothelial dysfunction (ED) is a common, early abnormality that predisposes patients to develop atherosclerosis and cardiovascular events; inflammation is associated with atherosclerosis and malnutrition. Patients with failed transplants are usually complicated by inflammation; however, ED in this group of patients has not been well defined. In this cross-sectional study, we sought to investigate ED among naïve peritoneal dialysis (nPD) patients who were never transplanted as well as patients with failed renal transplants who were re-starting peritoneal dialysis (fTxPD). Methods Twenty-five nPD patients (15 female/10 males; mean age, 44 ± 11 years), and 12 fTxPD patients (4 males; mean age, 37 ± 10 years) were included in the study. Coronary flow reserve (CFR) measurements were used to evaluate ED. Serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin, and intact parathyroid hormone (iPTH) were measured. Also, highly sensitive C-reactive protein (hs-CRP) levels and weekly Kt/V were determined as possible confounding factors. Results were compared between the 2 groups. Results There were no significant differences regarding age, gender, mean systolic and diastolic blood pressures, or smoking status. Mean duration on PD, peritoneal transport characteristics, PD modality and doses, frequency of peritonitis episodes, as well as serum creatinine, calcium, phosphorus, total cholesterol, albumin, hemoglobin and iPTH levels were similar between the 2 groups. Weekly Kt/V of both groups were similar as well. However, hs-CRP levels were significantly higher (34 ± 52 vs 6.7 ± 7.5 mg/L; P = .017) and CFR significantly lower among patients with fTxPD compared with nPD patients (1.52 ± 0.20 vs 1.91 ± 0.53; P = .022). Conclusion ED was more prominent among patients with failed transplants than nPD cases, suggesting that the failed allograft may be responsible for this abnormality.

Randomized Controlled Trial of Icodextrin versus Glucose Containing Peritoneal Dialysis Fluid

While peritoneal dialysis with icodextrin is commonly used in patients with poor peritoneal membrane characteristics, the data on the usefulness of this solution in patients with lower transport characteristics are limited. The study was designed to compare icodextrin to glucose in Chinese prevalent peritoneal dialysis patients of different peritoneal transport characteristics (PET) categories. This was a randomized, double-blind, perspective control study. Stable prevalent continuous ambulatory peritoneal dialysis (CAPD) patients were randomized to either 7.5% icodextrin (ICO) or 2.5% glucose (GLU) solution for 4 wk. Peritoneal membrane function was measured to define PET category in baseline. Creatinine clearance (Ccr), urea nitrogen clearance (C(BUN)), ultrafiltration (UF) during the long night dwell, dialysate, and metabolic biomarkers were measured at baseline, 2, and 4 wk. UF, Ccr, and C(BUN) were compared among different PET categories. A total of 201 CAPD patients were enrolled in the study. There were no baseline differences between the groups. Following 2 and 4 wk of therapy, Ccr, C(BUN,) and UF were all significantly higher in the ICO versus the GLU group. Additionally, switching to ICO resulted in a significant increase in UF in high, high-average, and low-average transporters as compared with baseline. The extent of increased UF was more obvious in higher transporters. Blood cholesterol level in the ICO group decreased significantly than that in the GLU group. Compared with glucose-based solution, 7.5% icodextrin significantly improved UF and small solute clearance, even in patients with low-average peritoneal transport.

The Innovation Issue

Summary Background and objectives Phosphate control impacts dialysis outcomes. Our aim was to define peritoneal phosphate transport in peritoneal dialysis (PD) and to explore its association with hyperphosphatemia, phosphate clearance (PPhCl), and PD modality. Design, setting, participants, & measurements Two hundred sixty-four patients (61% on continuous ambulatory PD [CAPD]) were evaluated at month 12. PPhCl was calculated from 24-hour peritoneal effluent. Phosphate (Ph) and creatinine (Cr) dialysate/plasma (D/P) were calculated at a 4-hour 3.86% peritoneal equilibration test. Results D/PPh correlated with D/PCr. PPhCl correlated better with D/PPh than with D/PCr. Prevalence of hyperphosphatemia (>5.5 mg/dl) was 30%. In a multiple regression analysis, only residual renal function was independently, negatively associated with hyperphosphatemia; in anuric patients, only D/PPh was an independent factor predicting hyperphosphatemia. D/PPh was 0.57 ± 0.10, and according to this, 16% of the patients were fast, 31% were fast-average, 35% were slow-average, and 17% were slow transporters. PPhCl was 37.5 ± 11.7 L/wk; it was lower in the slow transporter group (31 ± 14 L/wk). Among fast and fast-average transporters, PPhCl was comparable in both PD modalities. In comparison to automated PD, CAPD was associated with increased PPhCl among slow-average (36 ± 8 versus 32 ± 7 L/wk) and slow transporters (34 ± 15 versus 24 ± 9 L/wk). Conclusions In hyperphosphatemic, particularly anuric, patients, optimal PD modality should consider peritoneal phosphate transport characteristics. Increasing dwell times and transfer to CAPD are effective strategies to improve phosphate handling in patients with inadequate phosphate control on automated PD.

Icodextrin Improves Metabolic and Fluid Management in High and High-Average Transport Diabetic Patients

Icodextrin-based solutions (ICO) have clinical and theoretical advantages over glucose-based solutions (GLU) in fluid and metabolic management of diabetic peritoneal dialysis (PD) patients; however, these advantages have not yet been tested in a randomized fashion. To analyze the effects of ICO on metabolic and fluid control in high and high-average transport diabetic patients on continuous ambulatory PD (CAPD). A 12-month, multicenter, open-label, randomized controlled trial was conducted to compare ICO (n = 30) versus GLU (n = 29) in diabetic CAPD patients with high-average and high peritoneal transport characteristics. The basic daily schedule was 3 x 2 L GLU (1.5%) and either 1 x 2 L ICO (7.5%) or 1 x 2 L GLU (2.5%) for the long-dwell exchange, with substitution of 2.5% or 4.25% for 1.5% GLU being allowed when clinically necessary. Variables related to metabolic and fluid control were measured each month. Groups were similar at baseline in all measured variables. More than 66% of the patients using GLU, but only 9% using ICO, needed prescriptions of higher glucose concentration solutions. Ultrafiltration (UF) was higher (198 +/- 101 mL/day, p < 0.05) in the ICO group than in the GLU group over time. Changes from baseline were more pronounced in the ICO group than in the GLU group for extracellular fluid volume (0.23 +/- 1.38 vs -1.0 +/- 1.48 L, p < 0.01) and blood pressure (systolic 1.5 +/- 24.0 vs -10.4 +/- 30.0 mmHg, p < 0.01; diastolic 1.5 +/- 13.5 vs -6.2 +/- 14.2 mmHg, p < 0.01). Compared to baseline, patients in the ICO group had better metabolic control than those in the GLU group: glucose absorption was more reduced (-17 +/- 44 vs -64 +/- 35 g/day) as were insulin needs (3.6 +/- 3.4 vs - 9.1 +/- 4.7 U/day, p < 0.01), fasting serum glucose (8.3 +/- 36.5 vs -37 +/- 25.8 mg/dL, p < 0.01), triglycerides (54.5 +/- 31.9 vs -54.7 +/- 39.9 mg/dL, p < 0.01), and glycated hemoglobin (0.79% +/- 0.79% vs -0.98% +/- 0.51%, p < 0.01). Patients in the ICO group had fewer adverse events related to fluid and glucose control than patients in the GLU group. Icodextrin represents a significant advantage in the management of high transport diabetic patients on PD, improving peritoneal UF and fluid control and reducing the burden of glucose overexposure, thereby facilitating metabolic control.

Effect of using icodextrin as a starting therapy for peritoneal permeability

Peritoneal permeability differs between patients at the time of starting peritoneal dialysis (PD) and it can increase along with time on the technique. This fact is related to peritonitis, the biocompatibility of the dialysis fluids and the use of glucose as osmotic agent. The aim of the present study was to evaluate if the use of one exchange a day of icodextrine from the time of DP initiation affects the evolution of peritoneal permeability. 56 patients starting PD (mean age: 48.3 +/- 14.0; 62.5% males; 17.9% diabetics) that used one exchange a day with icodextrine from the time of starting PD. We performed a peritoneal transport kinetic study at the time of starting PD and then every 6 months during two years. We calculated the peritoneal mass transfer area coefficient of creatinine (Cr-MTAC) and urea (U-MTAC) as well as the D/P creatinine relationship (D/P Cr). As a control group we used the results of Cr-MTC of 249 patients that had used glucose as the only osmotic agent from the time of starting PD. The peritoneal transport, calculated using Cr-MTC, U-MTC and D/P Cr, diminished at 12 months (11.7+/-5.7 vs. 8.1+/-3.1; 23.5+/-7.3 vs. 18.9+/-3.8; 0.72+/-0.09 vs. 0.67+/-0.08; respectively), staying stable afterwards.We found that high transporters (HA) patients (higher quatril Cr-MTC ) showed a higher diminution of Cr-MTAC along the first year of treatment. The diminution of Cr-MTAC after 12 months using icodextrine was significantly higher (p<0.001) that the one observed in the control group that only used glucose as osmotic agent (10.5+/-5.3 vs. 10.1+/-4.6). We found that high transporters (HA) patients (higher quatril Cr-MTC) showed a higher decrease of Cr-MTAC along the first year of treatment. the use of icodextrine at the time of starting PD might help to correct the high transport status observed in some patients during the first months of treatment. The peritoneal transport kinetic studies performed at 6 and 12 months after starting PD are more representative of the long term peritoneal transport characteristics of the patients than those performed at the time of starting PD.

Difficulty in Improving Malnutrition and Low‐grade Inflammation in Diabetic Patients on Peritoneal Dialysis

Continuous ambulatory peritoneal dialysis (CAPD) is commonly used for renal replacement therapy in diabetes mellitus (DM) patients. We investigated the changes of peritoneal transport characteristics, nutritional status, and adequacy and inflammation parameters in diabetic CAPD patients (N = 17) compared to non-diabetic patients (N = 23). Peritoneal equilibrium testing, nutritional, biochemical, and anthropometric parameters and adequacy were prospectively assessed at 1 (baseline), 6 and 12 months after initiating CAPD. The levels of several nutritional parameters were lower and did not change in DM patients over time (P < 0.05) and significantly improved in the non-DM patients over time (P < 0.05). Total weekly creatinine clearance and residual renal function exhibited a rapid decline (P < 0.05) and inflammation parameter levels were higher in DM patients (P < 0.05). Our results showed the difficulty in improvement of nutritional status and inflammatory parameters in diabetic patients during at least the first year of CAPD compared to non-DM patients.

Peritoneal Phosphate Clearance is Influenced by Peritoneal Dialysis Modality, Independent of Peritoneal Transport Characteristics

Hyperphosphatemia is an independent risk factor for mortality in ESRD, but factors regulating phosphate clearance on peritoneal dialysis (PD) are incompletely understood. The objective of this study was to test the hypothesis that peritoneal phosphate clearance is better with continuous ambulatory PD (CAPD) as compared with continuous cyclic PD (CCPD) after adjusting for membrane transport status. In this cross-sectional and retrospective study, measurements of peritoneal phosphate clearance of 129 prevalent PD patients were reviewed. Patients were divided according to membrane transport status (high, high average, low average-low categories) and PD modality (CAPD or CCPD). Among high transporters, peritoneal phosphate clearances were comparable in both modalities. However, treatment with CAPD was associated with increased peritoneal phosphate clearance compared with CCPD among high-average transporters (42.4 +/- 11.4 versus 36.4 +/- 8.3 L/wk/1.73 m(2), P = 0.01), and low-average-low transporters (35.6 +/- 5.9 versus 28.9 +/- 11 L/wk/1.73 m(2), P = 0.034). On multivariate linear regression, PD modality, membrane transport category, and peritoneal creatinine clearance, but not Kt/V urea, were independently associated with peritoneal phosphate clearance. Peritoneal phosphate clearance is determined by PD modality and membrane transport category, suggesting that PD regimes with longer dwell times may help control hyperphosphatemia in lower transporters.

Experimental Study on Long-Term Exposure to a Biocompatible, Hypertonic, Pyruvate-Buffered Dialysis Solution

Chronic exposure to glucose and glucose degradation products (GDPs) in dialysis solutions is involved in the pathogenesis of peritoneal neoangiogenesis and fibrosis, potentially leading to encapsulating peritoneal sclerosis (EPS). High lactate concentrations may contribute to glucose toxicity by creating a state of pseudohypoxia, which stimulates the formation of various growth factors. To study the effects of long-term peritoneal exposure to a filter-sterilized pyruvate-buffered solution with a combination of 3 osmotic agents (amino acids, glycerol, glucose: PYRAGG) on peritoneal function and morphology. Rats were exposed daily for a period of 20 weeks to PYRAGG, or to a conventional heat-sterilized solution (LH), or to a filter-sterilized solution (LF), after which a peritoneal function test was done and peritoneal tissue was obtained. Peritoneal solute and fluid transport characteristics at 20 weeks were similar in all groups. Fibrosis was most pronounced in the LH group compared to the others, suggesting an effect of GDPs. A marked reduction in the number of omental vessels was noted in the PYRAGG group (59% reduction compared to LH). A modest reduction (28%) was found in the LF animals. This points to a marked effect of reduced exposure to glucose. PYRAGG was more biocompatible than a filter-sterilized glucose/lactate solution because it did not induce marked peritoneal abnormalities after long-term exposure. This did not lead to altered peritoneal transport characteristics. It is likely that further development of PYRAGG-like solutions will decrease the incidence of EPS.

The Role of the TGF/Smad Signaling Pathway in Peritoneal Fibrosis Induced by Peritoneal Dialysis Solutions

Background: Peritoneal dialysis (PD) solutions contribute to peritoneal membrane damage. We investigated how conventional and biocompatible PD solutions with different glucose concentrations affect morphological and functional signs of peritoneal fibrosis as well as the TGF-β1/Smad signaling pathway in a chronic PD rat model. Methods: Non-uremic male Wistar rats (n = 28) were dialyzed thrice daily for 28 days with 20 ml of a conventional solution (Dianeal® 1.36%, D1, or 3.86%, D3) or a biocompatible solution (Physioneal® 1.36%, P1, or 3.86%, P3). A peritoneal equilibration test was performed. Six rats without dialysis served as controls. Results: The use of conventional solutions, particularly D3, resulted in expansion of the submesothelial compact zone, loss of mesothelial cell layer integrity, hypercellularity, accumulation of collagen I, increased vessel numbers and increased TGF-β1/Smad expression, but this did not significantly change fluid and solute peritoneal transport characteristics. In comparison with D1 and D3, the use of P1 and P3 was associated with less TGF-β1/Smad expression and less expansion of the submesothelial cell layer. Conclusions: Our findings indicate that biocompatible solutions with less glucose may decrease the rate of peritoneal fibrosis. The TGF-β1/Smad pathway is stimulated by PD solutions, representing a plausible pathophysiological mechanism.

Factors Associated With Body-Fat Changes in Prevalent Peritoneal Dialysis Patients

Changes in body fat (BF) were shown to occur over time in peritoneal dialysis (PD) patients. However, the factors associated with BF changes have not been fully investigated in this population. We studied 45 patients (25 were male; age, 53, SD +/- 15 years; 21 continuous ambulatory peritoneal dialysis/24 automated peritoneal dialysis; PD vintage, 14 ([range, 3 to 104] months; 40% were diabetic; 31% were previously treated by hemodialysis). Body composition was assessed by dual-energy X-ray absorptiometry and bioelectric impedance analysis, nutritional status was assessed by subjective global assessment, energy intake was assessed by 3-day food records, and resting energy expenditure (REE) was assessed by indirect calorimetry. Glucose absorption, serum bicarbonate, and C-reactive protein were also evaluated. All measurements were performed at baseline and after 12 months. Large variability in BF changes was observed among patients: 53% gained BF (+3.0 +/- 2.8), whereas 47% lost BF (-2.3, SD +/- 1.4). At baseline, groups were similar regarding sex, age, percent diabetics, DP modality, characteristics of peritoneal transport, residual renal function, energy intake, glucose absorption, and REE. However, patients who gained BF had lower BF (16.3, SD +/- 6.9 kg, versus 20.9, SD +/- 6.5 kg; P = .03), had a higher ratio of total energy offered (intake plus absorbed glucose) to REE (1.45, SD +/- 0.39, versus 1.26, SD +/- 0.24; P = .04), and were on PD for a shorter time (10 [range, 3 to 104] versus 20 [range, 4 to 76] months; P = .03). This group also had a higher proportion of malnourished patients (50% versus 19%; P = .03) and of patients previously treated by hemodialysis (46% versus 14%; P = .03). After 12 months, a reduction in the frequency of malnutrition (50% to 25%; P = .02) was observed in the group of patients with increased BF. Patients who lost BF reduced their body cell mass (from 21.7 [SD +/- 5.1 kg] to 20.7 [SD +/- 5.0 kg]; P < .01) and level of serum bicarbonate (from 22.7 [SD +/- 3.7 mmol/L] to 20.9 [SD +/- 3.1 mmol/L]; P < .01). Moreover, this group had an increase in frequency of malnutrition (from 19% to 38%; P = .02), a reduction in the proportion of patients with residual renal function (from 62% to 43%; P = .03), and a higher number of hospitalizations (from 25% to 4%; P = .02) during follow-up. Glucose absorption and C-reactive protein were not associated with BF changes. A regression analysis showed that baseline body mass index was independently associated with a gain of BF (-0.19, SE = 0.09, P = .04), and that hospitalization during follow-up was associated with a loss of BF (2.35, SE = 1.19, P = .04). Prevalent PD patients exhibited a large variability in BF changes. Baseline body mass index and hospitalizations during follow-up were the most important factors associated with these changes.

The relationship between bone morphogenic protein-7 and peritoneal transport characteristics

After prolonged peritoneal dialysis (PD) and exposure to a non-physiological dialysis solution, peritoneal mesothelial cells undergo the epithelial-to-mesenchymal transition. In other biological systems, bone morphogenic protein-7 (BMP-7) is a key factor that controls this process. However, the role of BMP-7 in peritoneal physiology has not been studied. We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified. At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport. Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study.

Endotoxemia is Related to Systemic Inflammation and Atherosclerosis in Peritoneal Dialysis Patients

Systemic inflammatory state is a hallmark of peritoneal dialysis (PD) patients, but its etiology remains obscure. Because circulating microbial products are an important cause of systemic immune activation in other conditions such as HIV infection, it was hypothesized that endotoxemia is a cause of systemic inflammatory state and atherosclerosis in PD patients. Plasma lipopolysaccharide (LPS) levels in 30 consecutive new PD patients were measured. The result was compared with serum C-reactive protein (CRP) level, peritoneal transport status, history of pre-existing cardiovascular diseases, and carotid intima media thickness (IMT) by Doppler ultrasound. Among the 30 PD patients, there were 17 men. The average age was 53.7 +/- 15.1 yr. The average endotoxin concentration of PD patients was 0.44 +/- 0.18 EU/ml, which was significantly higher than that of patients with chronic kidney disease secondary to Ig-A nephropathy (IgAN) (0.035 +/- 0.009 EU/ml, P < 0.0001) and the controls (0.013 +/- 0.007 EU/ml, P < 0.0001). In PD patients, plasma LPS concentration had a significant correlation with serum CRP (r = 0.415, P = 0.025) and serum albumin level (r = -0.394, P = 0.034). In contrast, plasma LPS level did not correlate with Charlson's Comorbidity Index, peritoneal transport characteristics, or nutritional indices. Patients with pre-existing cardiovascular disease (CVD) had higher plasma LPS level than those without CVD (0.53 +/- 0.19 versus 0.36 +/- 0.16 EU/ml, P = 0.016). Plasma LPS level correlated with carotid IMT (r = 0.438, P = 0.016). It was found that endotoxemia was probably common in PD patients, and the degree of circulating endotoxemia might be related to the severity of systemic inflammation and features of atherosclerosis. This result suggests that endotoxemia may have a contributory role to the systemic inflammatory state and accelerated atherosclerosis in PD patients.

The Prescription of Peritoneal Dialysis

In addition to the maintenance of normal extracellular electrolyte composition, the prescription of continuous peritoneal dialysis (CPD) should address four other specific issues: (i) prevention of uremia by achievement of adequate clearance of azotemic substances, (ii) prevention of progressive expansion of the extracellular volume by adequate peritoneal ultrafiltration, (iii) prevention of loss of residual renal function, and (iv) prevention of deterioration of the peritoneal membrane structure and function. Urea clearance, in the form of Kt/V(Urea), is the index of removal of azotemic substances proposed by current guidelines. The target total (renal plus peritoneal) Kt/V(Urea) is >or=1.7 weekly. To provide the desired peritoneal Kt/V(Urea) (K(p)t/V(Urea)), the prescription of peritoneal dialysis must provide a daily drain volume (Dv) defined by the clearance equations as Dv = V x (K(p)t/V(Urea))/(D/P(Urea)), where V is body water obtained from published anthropometric formulas, K(p)t/V(Urea) = (1.7 - renal Kt/V(Urea))/7 and D/P(Urea) is the dialysate-to-plasma urea concentration ratio at the dwell time prescribed. Computer programs obtain the relevant D/P(Urea) values from formal studies of peritoneal transport. In the absence of these studies (for example, at initiation of CPD), D/P(Urea) values can be obtained from published studies with similar dwell times. Body size, indicated by V, is the major determinant of the K(p)t/V(Urea) limit provided by a given CPD schedule. Other obstacles to achievement of adequate urea clearance are created by poor patient compliance, inaccuracies of the anthropometric formulas estimating V, and mechanical complications of CPD that lead to retention of dialysate in the body. The main requirements for the prescription of adequate ultrafiltration are knowledge of the individual peritoneal transport characteristics, monitoring of urinary volume, and restriction of dietary sodium intake. Excessive dietary sodium intake is the major cause of extracellular volume expansion in CPD. Ideally, sodium intake should be kept at the level of total (peritoneal plus renal) sodium removal. Preventing the loss of residual renal function involves avoidance of nephrotoxic influences in the form of medications, radiocontrast agents, urinary obstruction and infection, and possibly other influences, such an elevated calcium-phosphorus product and anemia. Use of the lowest dialysate dextrose concentration that will allow adequate ultrafiltration is currently the most widespread practical measure of prevention of peritoneal membrane deterioration. Formulation of biocompatible dialysate is a major ongoing research effort and may greatly enhance the success of CPD in the future.

TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

Transforming growth factor-β1 (TGF-β1) stimulates the expression of collagen mRNA in cultured human peritoneal mesangial cells, which may predispose them to developing peritoneal fibrosis. Polymorphisms in the signal sequence genetically may be responsible for increased TGF-β1 production (i.e., a substitution at amino acid position 10 and 25, +869 Leu10–Pro and +915 Arg25–Pro, respectively). The aim of this study was to find out whether there is any relation between peritoneal equilibration test (PET) results and TGF-β1 gene polymorphism. Thirty-two CAPD patients and 72 healthy subjects were included into the study. Each CAPD patient had undergone two PET with a two-year interval. The patients were classified according to the results of a baseline PET as high (high-high average) and low (low-low average) transporters. In high transporters group (n = 20), the genotype frequencies were found as 45% Leu/Leu, 55% Leu/Pro for codon 10; and 85% Arg/Arg, 15% Arg/Pro for codon 25. In low transporters group (n = 12), the genotype frequencies were detected as 66.7% Leu/Leu and 33.3% Leu/Pro for codon 10; and 83.3% Arg/Arg, 16.7% Arg/Pro for codon 25. The distribution of the TGF-β1 genotypes in our control population was compatible with a Hardy-Weinberg equilibrium. We found no relation between TGF-β1 genotypes and peritoneal transport group (χ2 test, p > 0.5). There was no relation between TGF-β1 genotype and longitudinal change in peritoneal transport. This study is the first study analyzing the possible link between TGF-βl gene polymorphisms and the characteristics of peritoneal transport and longitudinal change of peritoneal transport characteristics in CAPD patients. Further work is needed to clarify the functional importance of these two polymorphisms in TGF-β1 production and in the development of peritoneal fibrosis.