Peritoneal Solute Transport Rate Research Articles

Contribution of Residual Renal Function on Peritoneal Solute Transport in Dialysis Patients

Background: Increased peritoneal solute transport rate (PSTR) is primarily a consequence of continuous exposure to bioincompatible glucose-based peritoneal dialysis (PD) solutions. However, relationships between increasing PSTR and dialysate glucose load remain unclear. As some PD patients with preserved residual renal function do not show increased PSTR despite long-term PD, we examined whether loss of residual renal function is associated with increased PSTR on long-term PD. Methods: We evaluated 35 patients who started PD between 1997 and 2002 and received continuous PD treatment for >6 years. Data included baseline clinical data, residual renal function, urea and creatinine clearance, dialysate glucose load, ultrafiltration, and the use of icodextrin and renin-angiotensin system inhibitors. Peritoneal equilibration test results and data were collected annually for 6 years. Results: Both the glomerular filtration rate and urine volume at 6 years on PD showed significant negative correlations with the dialysate-to-plasma creatinine ratio (D/P Cr) at 6 years (r = –0.716 and r = –0.717, respectively). Multivariate analysis showed only urine volume at 6 years on PD as an independent covariate of the D/P Cr at 6 years on PD. Conclusions: Loss of residual renal function is directly associated with increased PSTR in patients on long-term PD.

Impact of systemic and local peritoneal inflammation on peritoneal solute transport rate in new peritoneal dialysis patients: a 1-year prospective study

The association between peritoneal solute transport rates (PSTRs) and inflammatory markers in patients on peritoneal dialysis (PD) is still under investigation. We aimed to elucidate their relationship during the first year on PD. We performed a prospective observational study with 187 incident PD patients who were treated with either biocompatible solution (BCS) or conventional solution (CS). Peritoneal dialysate effluent (PDE) and blood samples for the markers and the calculation of mass transfer area coefficient of creatinine (MTAC) were performed at 1, 6 and 12 months after commencing PD. Of the 187 enrolled patients, 110 completed a 1-year study protocol. All PDE markers [interleukin-6 (IL-6), transforming growth factor-beta (TGF-beta), TGF-beta-induced gene-h3 (beta ig-h3), vascular endothelial growth factor (VEGF)] except CA125 increased over time, whereas PSTRs, high-sensitivity C-reactive protein (hs-CRP) and serum IL-6 levels did not change. Serum albumin and log PDE appearance rates (ARs) of IL-6, TGF-beta and CA125 predicted MTAC. The Delta value (12-month minus 1-month) of PDE AR of IL-6 was correlated with those of all other PDE markers. Both 12-month IL-6 and Delta IL-6 ARs in PDE were highest in the upper Delta MTAC tertile. PSTRs in the CS group, unlike BCS, had a tendency to increase over time, demonstrating a time-by-group interaction. Solution type and MTAC were not associated with patient and technique survival. The change in PSTR during the first year of PD is related to PDE IL-6 AR, which may represent intraperitoneal inflammation; however, there does not seem to be a close association between PSTR and the degree of systemic inflammation.

Intra-peritoneal interleukin-6 system is a potent determinant of the baseline peritoneal solute transport in incident peritoneal dialysis patients

Interleukin-6 (IL-6) is a key player in modulating inflammation. IL-6 and soluble IL-6 receptor (sIL-6R) complex induces the synthesis and secretion of various chemokines, adhesion molecules and angiogenic molecules. We hypothesized that the baseline peritoneal solute transport rate (PSTR) early after commencing peritoneal dialysis (PD) may depend largely on the IL-6/sIL-6R system. We also hypothesized that the dialysate concentrations of IL-6/sIL-6R could be closely related to local inflammation or angiogenesis in the peritoneal cavity. Fifty incident patients with a modified peritoneal equilibration test result within 3 months after commencing PD and without a previous history of peritonitis were enrolled. Clinical parameters such as age, sex, comorbid disease, body mass index, residual renal function and C-reactive protein were assessed. Serum and dialysate markers including CA125, IL-6, sIL-6R, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were measured and correlated with PSTR. Dialysate concentrations of IL-6 (r = 0.576, P < 0.001), MCP-1 (r = 0.408, P = 0.003) and Ang-2 (r = 0.408, P = 0.003) correlated with mass transfer area coefficient for creatinine (MTAC(cr)), respectively. Dialysate appearance rate (AR) of albumin correlated with dialysate concentrations of CA125 (r = 0.751, P < 0.001), IL-6 (r = 0.303, P = 0.039), sIL-6R (r = 0.497, P < 0.001), MCP-1 (r = 0.488, P < 0.001), VEGF (r = 0.443, P = 0.004) and Ang-2 (r = 0.488, P < 0.001). Neither MTAC(cr) nor AR of albumin was associated with systemic markers. Multivariate analysis showed that MTAC(cr) is independently associated with dialysate IL-6 and serum albumin. It also showed that AR of albumin is independently predicted by dialysate sIL-6R. Dialysate IL-6 correlated with dialysate concentrations of CA125 MCP-1, VEGF and Ang-2. Our study from incident PD patients suggested that (i) dialysate the IL-6 system is a potent determinant of baseline PSTR and (ii) elevation of IL-6 in the dialysate is associated with up-regulation of intra-peritoneal inflammatory and angiogenic molecules.

Connective tissue growth factor (CTGF/CCN2) is increased in peritoneal dialysis patients with high peritoneal solute transport rate

Peritoneal fibrosis (PF) is an important complication of peritoneal dialysis (PD) therapy that often occurs in association with peritoneal high transport rate and ultrafiltration failure (UFF). To study the possible pathogenic role of connective tissue growth factor (CTGF) in the relationship of PF and UFF, dialysate CTGF contents (n = 178) and tissue CTGF expression (n = 61) were investigated by ELISA, real-time PCR, immunohistochemistry, and in situ hybridization. CTGF production with and without TGF-beta1 stimulation in human peritoneal mesothelial cells (HPMC) from the spent patients' peritoneal dialysate (n = 32) was studied in vitro. The dialysate-to-plasma ratio for creatinine (D/P Cr) was positively correlated to dialysate CTGF concentration and estimated local peritoneal production of CTGF. CTGF mRNA expression was 11.4-fold higher in peritoneal membranes with UFF than in pre-PD renal failure peritoneum and was correlated with thickness of the peritoneum. CTGF protein and mRNA were detected in mesothelium and in fibroblast-like cells. In cultured HPMC, TGF-beta(1)-induced expression of CTGF mRNA was increased at 12 and 24 h and was correlated with D/P Cr. In contrast, bone morphogenic protein-4 mRNA expression was inversely correlated with D/P Cr. Our results suggest that high peritoneal transport state is associated with fibrosis and increased peritoneal CTGF expression and production by mesothelial cells, which can be stimulated by TGF-beta1. Dialysate CTGF concentration could be a biomarker for both peritoneal fibrosis and membrane function. Functional alteration of mesothelial cells may be involved in progression of peritoneal fibrosis in high transport state.

Benefits of biocompatible PD fluid for preservation of residual renal function in incident CAPD patients: a 1-year study

In vitro studies of peritoneal dialysis (PD) solutions demonstrated that a biocompatible fluid with neutral-pH and low glucose degradation products (LF) has better biocompatibility than a conventional acidic lactate-buffered fluid (CF). However, few clinical trials have investigated the effects of the biocompatible solution on residual renal function (RRF). We performed a prospective, randomized trial with patients starting continuous ambulatory peritoneal dialysis (CAPD). Ninety-one incident patients started CAPD for 12-month treatment with either LF (Balance, Fresenius, n = 48) or CF (CAPD/DPCA, Fresenius, n = 43). RRF, peritoneal solute transport rate and solute clearance were measured every 6 months. LF had a significant effect on the change of glomerular filtration rate (GFR) (P = 0.048 by the mixed model). In per-protocol analysis, GFR in the LF group did not decrease over a 12-month period, while GFR in the control group significantly decreased (0.13 +/- 33.4 L/ week/1.73 m(2) for LF versus -13.6 +/- 19.4 L/week/1.73 m(2) for CF, P = 0.049). Subgroup analysis for patients with initial GFR of 2 mL/min/1.73 m(2) or above showed a significantly higher GFR for the LF group over the 12-month period. At Month 13, serum total CO(2) levels were higher and serum albumin levels were lower in the LF group. No differences between the two groups were observed for the C-reactive protein. Over the 12-month period, effluent cancer antigen-125 levels significantly increased in the LF group, compared with those of the CF group, while effluent interleukin-6 levels were not different between the two groups. Our study suggests that LF may better preserve RRF over the 12-month treatment period in incident CAPD patients.

Effects of Interleukin-6 T15A Single Nucleotide Polymorphism on Baseline Peritoneal Solute Transport Rate in Incident Peritoneal Dialysis Patients

To study the genetic effects of various inflammatory cytokines on peritoneal solute transport rate (PSTR) in incident Korean peritoneal dialysis (PD) patients. Case-control association study. 132 patients with baseline peritoneal equilibration test within 1-3 months after starting PD were enrolled. We analyzed the influence of single nucleotide polymorphisms (SNPs) of interleukin-6 (IL-6; -572G/C, T15A), tumor necrosis factor-alpha (TNF-alpha; -1031C/T, -863C/A, -308G/A), and IL-10 (-1082A/G, -592A/C) on baseline PSTR. Clinical parameters such as age, gender, presence of diabetes mellitus, comorbidity, C-reactive protein, and residual renal function were also included as covariates. The T15A SNP of IL-6 (rs13306435) was associated with PSTR. Patients with TA genotype (n=18) had significantly lower D4/P creatinine (0.65+/-0.087 vs 0.73+/-0.110, p=0.0046) and higher D4/D0 glucose (0.39+/-0.174 vs 0.31+/-0.119, p=0.027) than patients with TT genotype (n=114). The log value of the dialysate appearance rate of IL-6 had a strong positive correlation with D4/P creatinine (r2=0.1294, p<0.0001) and was significantly lower in the TA genotype than the TT genotype (201.7+/-14.42 vs 116.8+/-88.91 pg/minute, p=0.0358). By multiple logistic regression, TA genotype was negatively associated with a higher PSTR (high or high average; odds ratio 0.18; 95% confidence interval 0.048-0.666). In incident Korean PD patients, T15A polymorphism of IL-6 is associated with dialysate IL-6 concentration and baseline PSTR.

Increased Dialysate Levels of Phospholipids Containing Unsaturated Fatty Acid Are Associated with Increased Peritoneal Transport Rate

High peritoneal transport status in end-stage renal disease patients receiving peritoneal dialysis was shown to be associated with increased morbidity and mortality. Although the pathogenesis of increased peritoneal transport is still not clear, previous studies have demonstrated that phospholipids (PLs) are present on the peritoneal mesothelium and when added to dialysate can decrease the peritoneal fluid absorption rate and increase peritoneal fluid removal. In the present report, we explored the relationship between peritoneal transport and dialysate loss of endogenous PLs.We evaluated 48 prevalent continuous ambulatory peritoneal dialysis patients with high or low peritoneal transport in a cross-sectional study. The 4-hour dwell dialysate PL profile was analyzed by high-performance liquid chromatography coupled with electrospray ionization ion trap mass spectrometry. The patients' peritoneal small solute transport rate was assessed by D/P(Cr) at 4 h and their fluid transport by kinetic modeling.While there were no significant differences between the 2 groups in age, sex, diabetic status and time on dialysis, high transporters had a significantly higher D/P(Cr) and peritoneal fluid absorption rate (K(e)) than low transporters. The PLs in dialysate effluents mainly consisted of PLs containing unsaturated fatty acid, and the concentrations, as well as the amount, of PLs were significantly elevated in the dialysate of high transporters as compared to low transporters.Our results showed that dialysate from high transporters exhibited elevated levels of PLs, especially PLs containing unsaturated fatty acid, suggesting a possible loss of peritoneal surface-active PLs in peritoneal dialysis, and this loss may contribute to the alteration in peritoneal transport.

Vascular Endothelial Growth Factor in Dialysate in Relation to Intensity of Peritoneal Inflammation

Peritoneal inflammation may induce changes in peritoneal microvessels, including neoangiogenesis/vasculogenesis, leading to increased peritoneal solute transport rate (PSTR) and loss of ultrafiltration capacity. We hypothesized that an inflammatory reaction in the peritoneal cavity during peritonitis induces increased synthesis of vascular endothelial growth factor (VEGF). We therefore studied the relationship between peritoneal inflammation markers, VEGF, and transport of fluid and solutes in rats during acute peritoneal inflammation induced by lipopolysaccharide (LPS) added to standard glucose-based dialysis solution. Under ether anesthesia, male Wistar rats were injected intraperitoneally with 30 mL Dianeal 3.86% without (Control; n=6) or with LPS (microg/mL): 0.001 (LPS 0.001; n=6), 0.01 (LPS 0.01; n=7), 0.1 (LPS 0.1; n=7), 1.0 (LPS 1.0; n=8). After 8 hours, dialysate volume (IPV), peritoneal solute transport rate (PSTR) and dialysate cell count (DCC) were measured and effluent samples were collected. LPS i.p. resulted in increased PSTR and decreased IPV (p<0.005). DCC (cells/microL) and the neutrophil/macrophage ratio were higher for all LPS concentrations compared to the control group. After 8 hours, LPS-exposed rats had significantly higher dialysate levels of all investigated cytokines (TNF-alfa, MCP-1 and IL-10) than the control group. Addition of LPS resulted in increased dialysate VEGF concentrations (pg/mL) (LPS 0.001, 28.2+/-5.9; LPS 0.01, 38.9+/-11.6; LPS 0.1, 43.0+/-5.9; LPS 1.0, 46.6+/-11.3; Control, 14.5+/-9.8; p<0.0005 for all LPS vs. Control). The infusion of Dianeal 3.86% with different doses of LPS induced a strong acute intraperitoneal inflammatory reaction with increased DCC and cytokine levels, resulting in increased peritoneal solute transport and decreased IPV. LPS induced a dose-dependent parallel increase of the intraperitoneal concentrations of MCP-1, IL-10 and TNF-alfa, as well as of VEGF. These results suggest that intraperitoneal VEGF synthesis is induced in response to inflammation, and that this may be an important component in the process leading to peritoneal transport alterations.

Baseline peritoneal solute transport rate is not associated with markers of systemic inflammation or comorbidity in incident Korean peritoneal dialysis patients

It is controversial whether comorbid status or systemic inflammation has an influence on the peritoneal solute transport rate (PSTR). Our aim is to elucidate whether baseline PSTR is associated with markers of systemic inflammation or degree of comorbidity in incident peritoneal dialysis (PD) patients. One hundred and ninety-five incident PD patients were prospectively included. Results of their baseline peritoneal equilibration test (PET) using 3.86% glucose PD fluid were analysed. Clinical and laboratory parameters of inflammation, comorbidity, nutritional status, dialysis adequacy and residual renal function (RRF) were assessed at the time of PET. Mean dialysate-to-plasma ratio for creatinine at 4 h (D/Pcr(4)) of our patients was 0.72 +/- 0.11. High-sensitivity C-reactive protein (hsCRP), serum interleukin-6 (IL-6) and serum albumin concentrations were closely interrelated to one another and these markers of systemic inflammation were also related to the Davies comorbidity score. No differences in age, sex ratio, body mass index, body surface area and presence of diabetes were found among four transport groups. RRF, total Kt/V, haemoglobin, nitrogen appearance and the Davies comorbidity score were not different either. High-sensitivity CRP, serum IL-6 and albumin concentrations were not associated with the baseline PSTR. By multiple linear regression analysis, only the serum albumin concentration measured at the time of PET (beta = -0.081 +/- 0.020, P < 0.001) remained significantly associated with D/Pcr(4). In our study with incident Korean PD patients, the baseline PSTR was not influenced by markers of systemic inflammation or comorbidity. For a subgroup of PD patients without serious comorbidity, other mechanisms of high baseline PSTR need to be elucidated.

Association Between Arterial Stiffness and Peritoneal Small Solute Transport Rate

While cardiovascular disease accounts for 40-50% of the mortality in dialysis patients, and while a high peritoneal transport in continuous ambulatory peritoneal dialysis (CAPD) is an independent predictor of outcome, it is unclear if there are any links. Aortic stiffness has become established as a cardiovascular risk factor. We thus studied pulse wave velocity (PWV) in CAPD patients to explore the possible link between peritoneal small solute transport and aortic stiffness. CAPD patients (n = 76, 27 M/49 F) in our center were included in the present study. Aortic stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral PWV. Patients' peritoneal small solute transport rate was assessed by D/P(cr) at 4 h. Extracellular water over total body water (E/T ratio) was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Carotid-femoral PWV was positively associated with patients' age (r = 0.555; P < 0.01), time on peritoneal dialysis (r = 0.332; P < 0.01), diabetic status (r = 0.319; P < 0.01), D/P(cr) (r = 0.241; P < 0.05), PP (r = 0.475; P < 0.01), and E/T (r = 0.606; P < 0.01). In a multivariate regression analysis, carotid-femoral PWV was independently determined by E/T (P < 0.01), PP (P < 0.01), age (P < 0.01), and D/P(cr) (P < 0.05). D/P(cr), in addition to E/T, age, and PP, was an independent predictor of elevated carotid-femoral PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased peritoneal small solute transport rate.

Plasma S100A12 Concentrations in Peritoneal Dialysis Patients and Subclinical Chronic Inflammatory Disease

S100A12 is a ligand for the receptor for advanced glycation end products. It has been shown that S100A12 induces expression of adhesion molecules, and mediates activation and migration of monocytes/macrophages. Circulating S100A12 may be involved in chronic inflammation. We previously reported increased S100A12 levels in patients with non-insulin-dependent diabetes mellitus and hemodialysis. A high peritoneal solute transport rate may be associated with encapsulating peritoneal sclerosis and mortality. We measured plasma S100A12 levels in peritoneal dialysis patients and evaluated a possible relation between the increased plasma S100A12 levels in peritoneal dialysis patients and the high peritoneal solute transport rate. Subjects included 36 patients (mean age +/- SE, 46.0 +/- 12.0 years) with no apparent infection and no malignancy who had been undergoing peritoneal dialysis for 36.5 +/- 3.9 months. We developed an enzyme-linked immunosorbent assay system to measure plasma S100A12 levels. A peritoneal equilibrium test was performed and subjects were categorized as high and high-average (H) (n = 14) or low and low-average (L) (n = 22) transporters. Plasma S100A12 concentrations were significantly higher in peritoneal dialysis patients (21.6 +/- 3.0 ng/mL) than in control subjects (n = 42; 10.8 +/- 1.0 ng/mL). Plasma S100A12 concentrations were also higher in the H group (28.2 +/- 6.1 ng/mL) than in the L group (14.2 +/- 2.0 ng/mL). These results suggest that S100A12 may be a sensitive marker of subclinical inflammation and that an increased S100A12 level may be related to the high peritoneal solute transport rate.

Correlation of Metabolic Syndrome with Residual Renal Function, Solute Transport Rate and Peritoneal Solute Clearance in Chronic Peritoneal Dialysis Patients

Background: Metabolic syndrome (MetS) and insulin resistance (IR) strongly promote macrovascular complications and endothelial dysfunction. They accelerate the progression of renal dysfunction in chronic kidney disease patients. However, their correlation with residual renal function (RRF) and peritoneal characteristics have never been investigated. Methods: The inter-relationships of IR (homeostatic model assessment, HOMA_IR), serum adiponectin level, body mass index (BMI), highly sensitive C-reactive protein (hs-CRP), RRF, peritoneal solute clearance (Kt/V_urea) and solute transport rate of 104 chronic peritoneal dialysis (PD) patients were examined. Results: Patients with (n = 57) and without (n = 47) clinically diagnosed MetS had the same degree of RRF, peritoneal Kt/V_urea, and solute transport rate. Higher HOMA_IR (p = 0.011), BMI (p = 0.01) and hs-CRP (p = 0.032), as well as lower adiponectin (p = 0.019), were associated with lower peritoneal Kt/V_urea. Serum adiponectin was negatively associated with solute transport rate (p = 0.02). In multiple regression analysis, higher HOMA_IR (p = 0.005), BMI (p = 0.021) and hs-CRP (p < 0.001) correlated with lower peritoneal Kt/V_urea. Conclusions: MetS plays an important role in both macrovascular complications and endothelial dysfunction in chronic PD patients, which correlates with changes in peritoneal solute clearance and solute transport rate but not RRF.

Peritoneal Small Solute Transport Rate Is Related to the Malnutrition Inflammation Score in Peritoneal Dialysis Patients

Background/Aims: A high peritoneal membrane transport status and peritoneal albumin leakage are determinants of morbidity and mortality in patients receiving continuous ambulatory peritoneal dialysis. In this study, we analyzed the relationship between the malnutrition inflammation score, peritoneal transport status, and 24-hour peritoneal albumin leakage in patients receiving peritoneal dialysis. Methods: Sixty-six patients receiving peritoneal dialysis (male-female ratio 30/36; age 46.2 ± 14.1 years; mean duration of peritoneal dialysis 32.4 ± 23.9 months) who had experienced no attacks of peritonitis within the prior 6 months were included. Results: The malnutrition inflammation score was positively correlated with the serum C-reactive protein concentration, dialysate/plasma creatinine ratio, and 24-hour peritoneal albumin leakage. Triceps and biceps skinfold thicknesses and serum concentrations of prealbumin, total cholesterol, and triglyceride were negatively correlated with the malnutrition inflammation score. Multiple linear regression analysis showed that the malnutrition inflammation score was independently associated with the dialysate/plasma creatinine ratio (p = 0.039) and 24-hour peritoneal albumin amount (p = 0.005). Conclusion: High peritoneal transport status and peritoneal albumin leakage are significantly associated with the malnutrition inflammation score.

Association between Arterial Stiffness and Peritoneal Fluid Kinetics

Background: A high peritoneal transport status in continuous ambulatory peritoneal dialysis (CAPD) patients is associated with a markedly increased morbidity and mortality. While the causes are as yet unknown, overall the proportion of deaths due to cardiovascular disease is estimated at 40–50% among dialysis patients. Arterial stiffness has been established as a cardiovascular risk factor, while the links between peritoneal transport status and aortic stiffness have not yet been investigated. Methods: We included 65 prevalent CAPD patients (24 males/41 females) from our center in a cross-sectional study. Arterial stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (C-F PWV). The patients’ peritoneal fluid transport was assessed by kinetic modeling. The patients’ peritoneal small solute transport rate was assessed by D/P_cr at 4 h. Extracellular water to total body water (E/T) ratio was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Results: C-F PWV was positively correlated with patients’ age (r = 0.489, p < 0.01), diabetic status (r = 0.327, p < 0.01), peritoneal fluid absorption rate (Ke; r = 0.251, p < 0.05), PP (r = 0.483, p < 0.01), and E/T (r = 0.517, p < 0.01). Multivariate regression analysis showed that C-F PWV was independently related to E/T (p < 0.01), PP (p < 0.01), age (p < 0.05), and Ke (p < 0.05). Conclusion: Peritoneal fluid transport (Ke), as well as E/T, age and PP were found to be independent predictors of elevated C-F PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased Ke rate, hypothetically through generalized vasculopathy.

Editorial: Poor Outcomes for Fast Transporters on PD: The Rise and Fall of a Clinical Concern

AbstractA rapid peritoneal solute transport rate (PSTR), generally termed a “high” PSTR, may in fact be associated with low small solute transport due to the low ultrafiltration rates with which it is associated; the term “fast” PSTR has, therefore, been proposed as a more accurate descriptive term. During the 1990s several studies showed that fast PSTR was associated with high mortality—presumably because it may lead to fluid overload, nutritional and metabolic alterations but also because it may be associated with other risk factors such as cardiovascular disease, other comorbid diseases, and inflammation. However, the consensus of today is that a fast PSTR is not as critical for patient survival as previously thought but that the prognosis depend on the type of fast PSTR: Type 1—an early inherent type which is associated with increased mortality mainly because it is associated with comorbidity and inflammation; these patients would have a poor prognosis also if they were treated by hemodialysis. Type 2—an early inherent type with a large peritoneal surface area; and Type 3—a late acquired type with peritoneal membrane changes which develop with time on peritoneal dialysis (PD); these two types have a good prognosis provided that fluid balance is controlled using automated peritoneal dialysis (APD) and icodextrin‐based PD solution. Thus, with the increased use of APD and icodextrin, the prognosis of fast transporters now looks less bleak. Perhaps, it will be possible in the future to even demonstrate improved survival in the Type 2 and Type 3 fast transporters using APD and icodextrin. In addition, there is hope that the new PD solutions may prevent the development of fast PSTR as well as have a favorable impact on its complications.

Relationship Between the −374T/A Receptor of Advanced Glycation End Products Gene Polymorphism and Peritoneal Solute Transport Status at the Initiation of Peritoneal Dialysis

An increased peritoneal solute transport rate (PSTR) at baseline is well known to be associated with decreased patient and technique survival in patients undergoing peritoneal dialysis (PD). Recently, angiogenesis has been recognized to be associated with PSTR and peritoneal deterioration. To investigate genetic variations in genes related to angiogenesis, 30 incident PD patients were studied. Several single nucleotide polymorphisms of the vascular endothelial growth factor (VEGF), the endothelial nitric oxide synthase (eNOS) and the receptor for advanced glycation end product (RAGE) were analyzed by the pyrosequencing method. The dialysate-to-plasma ratio of creatinine (D/P Cr) obtained from a peritoneal equilibrium test (PET) during the first 12 months after initiation of PD was used for a marker of PSTR. The D/P Cr was assessed both as a continuous and as a categorical variable including high (H), high-average (HA), low-average (LA), and low (L). Baseline D/P Cr was 0.645 +/- 0.083. The RAGE -374 TA genotype had a significantly lower prevalence of the H/HA transporters than the TT genotype (20% vs 63%; P = 0.03). Genetic polymorphisms of the VEGF and eNOS were not associated with initial peritoneal transport type. The RAGE polymorphism may have a considerable effect on the basal PSTR. Further studies will be needed to confirm this hypothesis.

Maximizing the Success of Peritoneal Dialysis in High Transporters

This article reviews the current understanding of high transport status in the peritoneal dialysis population and emphasizes survival can be improved for high transporters. To address the current state of knowledge on high peritoneal membrane transport, the negative impact of an increased peritoneal solute transport rate is first discussed. The potential downside of high transport status, notably on survival outcomes (as supported by registry data and meta-analysis), is highlighted. Based on recent advances and clinical studies, ways of maximizing the success of peritoneal dialysis treatment in high transporters are discussed, and management strategies are proposed.

Combination of Crystalloid (Glucose) and Colloid (Icodextrin) Osmotic Agents Markedly Enhances Peritoneal Fluid and Solute Transport during the Long PD Dwell

Fluid and sodium removal is often inadequate in peritoneal dialysis patients with high peritoneal solute transport rate, especially when residual renal function is declining. We studied the effects of using simultaneous crystalloid (glucose) and colloid (icodextrin) osmotic agents on the peritoneal transport of fluid, sodium, and other solutes during 15-hour single-dwell exchanges using 3.86% glucose, 7.5% icodextrin, and a combination fluid with 2.61% glucose and 6.8% icodextrin in 7 prevalent peritoneal dialysis patients with fast peritoneal solute transport rate. The combination fluid enhanced net ultrafiltration (mean 990 mL) and sodium removal (mean 158 mmol) compared with 7.5% icodextrin (mean net ultrafiltration 462 mL, mean net sodium removal 49 mmol). In contrast, the 3.86% glucose-based solution yielded negligible ultrafiltration (mean -85 mL) and sodium removal (mean 16 mmol). The combination solution resulted in significantly improved urea (+41%) and creatinine (+26%) clearances compared with 7.5% icodextrin. A solution containing both crystalloid (glucose 2.61%) and colloid (icodextrin 6.8%) osmotic agents enhanced fluid removal by twofold and sodium removal by threefold compared with 7.5% icodextrin solution during a dwell of 15 hours, indicating that such a combination solution could represent a new treatment option for anuric peritoneal dialysis patients with high peritoneal solute transport rate.

The Effect of Dialytic Modalities on Clinical Outcomes in ESRD Patients with Familial Mediterranean Fever

Background. Familial Mediterranean fever (FMF) is an autosomal recessive disease seen primarily in Sephardic Jews, Turks, and Armenians. The disease manifests as recurrent attacks of fever and serositis. The most important complication of FMF is the development of renal failure due to AA type amyloidosis. There has not been extensive experience with renal replacement therapy in FMF amyloidosis. Nevertheless, there may be a concern about the possibility of higher rates of morbidity and mortality in amyloidotic patients maintained on chronic hemodialysis. Moreover, there is not enough experience regarding patients on chronic peritoneal dialysis. As a result, the best treatment modality of end-stage renal disease (ESRD) in these circumstances still remains unclear. This study aimed to compare the effect of hemodialysis and peritoneal dialysis modalities on clinical outcomes in ESRD patients associated with FMF amyloidosis. Methods. Forty FMF patients with ESRD due to amyloidosis were retrospectively analyzed. All 40 patients were on renal replacement therapy, 20 on hemodialysis (HD), 20 on peritoneal dialysis (PD). Peritoneal solute transport rates, weekly mean creatinine clearance, and daily mean ultrafiltration (UF) of the patients on chronic peritoneal dialysis were evaluated. Weekly dialysis durations, dialysis membrane properties, Kt/V values, interdialytic weight gains, and frequency of hypotension during dialysis were evaluated on hemodialysis patients. All of the patients were examined according to their demographic characteristics, laboratory results, duration time on dialysis, erythropoietin requirements, frequencies of infectious complications requiring hospitalization, and the two renal replacement modalities mentioned above were compared in terms of these parameters. Results. Serum albumin levels of the patients with FMF amyloidosis who were maintained on peritoneal dialysis treatment were lower (2.87 vs 3.45) and the frequency of infections of the same group was higher (4.2 vs 0.5) than the patients with ESRD secondary to other diseases in the CAPD group. Conclusions. This retrospective analysis showed that peritoneal dialysis may have some disadvantages in amyloidotic patients. Due to the high frequency of hypoalbuminemia and infectious complications seen in this group, peritoneal dialysis is widely accepted as an alternative choice of treatment when hemodialysis is not appropriate.

Meta-Analysis

Peritoneal membrane solute transport in peritoneal dialysis (PD) patients is assessed by the peritoneal equilibration test, which measures the ratio of creatinine in the dialysate to plasma after a standardized 4-h dwell (D/Pc). Patients then are classified as high, high-average, low-average, or low transporters on the basis of this result. A meta-analysis of observational studies was carried out to characterize the relationship between D/Pc and mortality and technique failure in patients who are on PD. Citations were identified in Medline by using a combination of Medical Subject Heading search terms and key words related to PD, peritoneal membrane permeability/transport, and mortality and technique failure. The table of contents of relevant journals and bibliographies of relevant citations were reviewed in duplicate. Twenty studies that met study criteria were identified. Nineteen studies were pooled to generate a summary mortality relative risk of 1.15 for every 0.1 increase in the D/Pc (95% confidence interval 1.07 to 1.23; P < 001). This result equated to an increased mortality risk of 21.9, 45.7, and 77.3% in low-average, high-average, and high transporters, respectively, as compared with patients with low transport status. Meta-regression analysis showed that the proportion of patients who were on continuous cycler PD within a study was inversely proportional to the mortality risk (P = 0.05). The pooled summary relative risk for death-censored technique failure was 1.18 (95% confidence interval 0.96 to 1.46; P = 0.12) for every 0.1 increase in the D/Pc. This meta-analysis demonstrates that a higher peritoneal membrane solute transport rate is associated with a higher mortality risk and a trend to higher technique failure.