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Introduction Residual renal function (RRF) plays an important role in outcome of peritoneal dialysis (PD) including mortality. It is, therefore, important to provide a strategy for the preservation of RRF. The objective of this study was to evaluate relative protective effects of new glucose-based multicompartmental PD solution (PDS), which is well known to be more biocompatible than glucose-based conventional PDS, on RRF compared to conventional PDS by performing a systematic review (SR) of randomized controlled trials.Methods We searched studies presented up to January 2014 in MEDLINE, EMBASE, the COCHRANE library, and local databases. Three independent reviewers reviewed and extracted prespecified data from each study. The random effects model, a more conservative analysis model, was used to combine trials and to perform stratified analyses based on the duration of follow-up. Study quality was assessed using the Cochrane Handbook for risk of bias. Eleven articles with 1,034 patients were identified for the SR.Results The heterogeneity of the studies under 12 months was very high, and the heterogeneity decreased substantially when we stratified studies by the duration of follow-up. The mean difference of the studies after 12 months was 0.46 mL/min/1.73 m2(95% confidence interval = 0.25 to + 0.67).Conclusion New PDS showed the effect to preserve and improve RRF for long-term use compared to conventional PDS, even though it did not show a significant difference to preserve RRF for short-term use.

Objective Accumulation of visceral fat is one of the major risk factors for the development of cardiovascular disease in peritoneal dialysis (PD) patients. Adiponectin, an adipokine commonly regarded as a negative indicator of metabolic disease, is reported to be downregulated in its gene level in end-stage renal disease patients. Since excessive fat deposit is involved in increased reactive oxygen species (ROS), PD solution (PDS) may contribute to ROS production, resulting in dysregulation of adiponectin. In this study, we tested our hypothesis that oxidative stress induced by PDS may play a role in the regulation of adiponectin.Methods Commercial PDS containing 3.86% glucose (20 - 30 mL) was administered to SD rats for 12 weeks with and without N-acetylcysteine (NAC; 10 mmol/L). ELISA was used to quantify adiponectin in plasma and spent dialysate. For in vitrostudies, fully differentiated 3T3-L1 adipocytes and adipocytes isolated from abdominal fat were treated with a high glucose solution, PDS, and H2O2. Adiponectin levels in the conditioned media were measured by ELISA and immunoblot assays. The mRNA levels of adiponectin in mature adipocytes were examined using real-time RT-PCR.Results The levels of adiponectin in plasma and spent dialysate were significantly downregulated by PDS and this effect was suppressed by NAC. In 3T3-L1 adipocytes, adiponectin secretion was inhibited by 50 mmol/L glucose, PDS diluted 2-fold, and H2O2(200 μmol/L). In addition, H2O2downregulated expression of adiponectin mRNA and secretion of adiponectin oligomer complexes.Conclusions Our data suggest that ROS induced by conventional glucose-based PDS may contribute to pathophysiological changes in abdominal fat and down regulate adiponectin secreted from adipocytes during long-term PD.

Objective To demonstrate the presence of an independent renin–angiotensin system (RAS) in the peritoneum and to determine the role of locally produced angiotensin (Ang) II in high glucose-induced upregulation of transforming growth factor (TGF)-β1 and fibronectin by human peritoneal mesothelial cells (HPMC).Methods In cultured HPMC, the expression of mRNAs for angiotensinogen, angiotensin-converting enzyme (ACE), Ang II type 1 receptor (AT1), and TGF-β1 was evaluated by real-time polymerase chain reaction; ACE, AT1, and fibronectin proteins by Western blot analysis; and Ang I, Ang II, and TGF-β1 proteins by ELISA. Dichlorofluorescein (DCF)-sensitive cellular reactive oxygen species (ROS) were measured by fluorometry.Results HPMC constitutively expressed all the components of RAS, and 50 mmol/L D-glucose (high glucose) significantly increased angiotensinogen, ACE, and AT1 mRNAs and ACE, AT1, and Ang II proteins. Ang II increased TGF-β1 and fibronectin protein expression and DCF-sensitive cellular ROS. Losartan prevented Ang II-induced increase in cellular ROS. Both losartan and captopril inhibited high glucose-induced upregulation of TGF-β1 and fibronectin expression in HPMC in a dose-dependent manner. Antioxidant catalase and NADPH oxidase inhibitor diphenyleneiodinium effectively inhibited Ang II-induced TGF-β1 and fibronectin protein expression.Conclusions The present data demonstrate that HPMC constitutively express RAS, that Ang II produced by HPMC mediates high glucose-induced upregulation of TGF-β1 and fibronectin expression, and that Ang II-induced TGF-β1 and fibronectin expression in HPMC is mediated by NADPH oxidase-dependent ROS. These data suggest that locally produced Ang II and ROS in the peritoneum may be potential therapeutic targets in peritoneal fibrosis during long-term peritoneal dialysis.

♦ Objective To compare the effects of different peritoneal dialysis solutions (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming growth factor-β1(TGFβ1), procollagen I C-terminal peptide (PICP), procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human peritoneal mesothelial cells (HPMC).♦ Design Using M199 culture medium as control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare, Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P 4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E); Baxter] were tested. Growth-arrested and synchronized HPMC were continuously stimulated for 48 hours by test PDS diluted twofold with M199, TGFβ11 ng/mL, or different concentrations of icodextrin. VEGF, TGFβ1, and fibronectin secreted into the media were analyzed by ELISA, and PICP and PIIINP by radioimmunoassay.♦ Results Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E, significantly increased VEGF secretion compared with control M199. D 4.25- and P 4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and P 1.5, respectively, suggesting that high glucose may be involved in the induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting a role for glucose degradation products (GDP) in VEGF production. TGFβ1secretion was significantly increased by D 4.25 and E. Icodextrin increased TGFβ1secretion in a dose-dependent manner. All PDS tested significantly increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal 4.25-induced PIIINP secretion was significantly higher than P 1.5, again implicating high glucose and GDP in PIIINP secretion by HPMC. There was no significant increase in PICP or fibronectin secretion using any of the PDS tested. Addition of TGFβ11 ng/mL into M199 control significantly increased VEGF, PICP, PIIINP, and fibronectin secretion by HPMC.♦ Conclusions The present study provides direct evidence that HPMC can secrete VEGF, TGFβ1, and PIIINP in response to PDS, and that HPMC may be actively involved in the development and progression of the peritoneal membrane hyperpermeability and fibrosis observed in long-term PD patients. This study also suggests that both high glucose and GDP in PDS may play important roles in inducing VEGF and PIIINP production/secretion by HPMC.

Objective To investigate the biocompatibility of “new” peritoneal dialysis (PD) solutions with bicarbonate/lactate buffer, non glucose osmotic agents (icodextrin or amino acids), neutral pH, and low levels of glucose degradation products (GDPs).Design Using M199 culture medium as a control, we compared conventional and new PD solutions with respect to their effects on the viability of human peritoneal mesothelial cells (HPMCs) [using lactate dehydrogenase (LDH) release], on DNA damage in HPMCs [using single-cell gel electrophoresis (Comet assay)], and on HPMC proliferation (using [3H]-thymidine incorporation). The experiments were performed after cell growth was synchronized by incubation with serum-free media for 24 hours. The PD solutions tested included commercial 1.5% glucose and 4.25% glucose solutions with 40 mmol/L lactate (D 1.5 and D 4.25, respectively), 7.5% icodextrin (E), 1.1% amino acid (N), 1.5% glucose solution in a triple-chambered bag (Bio 1.5), 1.5% glucose solution in a dual-chambered bag with neutral pH (Bal 1.5), and 1.5% glucose and 4.25% glucose solution containing 25 mmol/L bicarbonate and 15 mmol/L lactate (P 1.5 and P 4.25, respectively).Results When HPMCs were continuously exposed to undiluted PD solutions, D 1.5, D 4.25, P 4.25, and E increased LDH release by more than 60% at 24 hours. All PD solutions tested increased LDH release by more than 75% at 96 hours. With 2-fold diluted PD solutions, only D 4.25 significantly increased LDH release at 96 hours, though not at 24 hours. When cells were exposed to undiluted PD solutions for 60 min and allowed to recover in M199 for up to 96 hours, LDH release was significantly higher at 24 – 96 hours in E (55% – 69%) and D 1.5 (48% –72%) as compared with control [M199 (18%)]. Release of LDH was significantly lower with PD solutions containing lower levels of GDPs than those in D 1.5, suggesting that GDPs may have a role in cell viability. The D solutions (D 1.5 and D 4.25) and E solution also induced significant DNA damage. Both LDH release and DNA damage by D and E were significantly attenuated by adjusting the solution pH to 7.4, suggesting that low pH may be implicated in PD solution–induced DNA damage and cell death. When diluted 2-fold, D 1.5, D 4.25, and P 4.25 decreased [3H]-thymidine incorporation to 43%, 34%, and 41% of control, respectively, at 24 hours and to 45%, 26%, and 35% of control, respectively, at 96 hours. When cells were exposed to undiluted PD solutions for 5 minutes and allowed to recover in M199 for up to 96 hours, D 1.5 and P 4.25—but not D 4.25—significantly inhibited cell proliferation at 24 hours. This effect was sustained up to 96 hours.Conclusions The present in vitrodata demonstrate that PD solutions with low pH, or high levels of GDPs, or both, promote HPMC death and DNA damage, and that PD solutions with high osmolality inhibit cell proliferation. Solutions with neutral pH, amino acids, and “low GDPs” appear to be more biocompatible than conventional PD solutions. These results require confirmation in in vivoanimal and clinical studies.

Objective This study reviews evidence that implicates high glucose (HG) in the pathogenesis of peritoneal fibrosis and proposes mechanisms potentially involved in the HG-induced peritoneal fibrosis that is observed in long-term peritoneal dialysis (PD) patients.Design Selected Western literature is reviewed, examining the effect of HG on rat or human peritoneal mesothelial cell (HPMC) biology with particular reference to extracellular matrix (ECM) gene expression and protein synthesis.Results HG up-regulated the expression of monocyte chemotactic peptide–1 (MCP-1), transforming growth factor beta 1 (TGFβ1), and fibronectin messenger RNAs (mRNAs) and proteins. These HG-induced up-regulations were effectively blocked by the inhibition of protein kinase C (PKC). In addition, cytosolic reactive oxygen species (ROS) rapidly increased in HPMC cultured under HG, and treatment with antioxidant effectively inhibited HG-induced fibronectin protein synthesis by HPMC.Conclusion Continuous exposure of the peritoneal membrane to HG may induce changes in HPMC biology, leading to excessive deposition of ECM and peritoneal injury. HG-induced activation of diacylglycerol PKC (DAG–PKC) plays a major role in up-regulation of MCP-1, TGFβ1, and fibronectin synthesis by HPMC cultured under HG. In addition, ROS, recently recognized as signalling molecules, are rapidly generated in HPMC as a result of increased glucose metabolism and may prove to be an important mediator of HG-induced peritoneal injury.

The survival of patients with end-stage renal disease (ESRD) resulting from diabetes continues to improve, but the survival rate among diabetic ESRD patients remains the lowest among all primary diagnoses probably because of the higher prevalence of cardiovascular comorbidity associated with diabetes. Diabetes, age, and comorbidity all significantly modify the effect of treatment modality on patient survival.As compared with hemodialysis (HD), peritoneal dialysis (PD) offers an equal or lower risk of death across all subgroups during the first 1 – 2 years of dialysis. The association of PD with better outcomes than are seen with HD is probably a result of a lower prevalence of infections and congestive heart failure and better preservation of residual renal function (RRF) in PD patients.Use of angiotensin converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) helps to preserve RRF in ESRD patients and to maintain peritoneal membrane integrity longer in PD patients. Antioxidants can also support preservation of peritoneal membrane function.Peritoneal dialysis should be the initial modality of dialysis in all ESRD patients. Older patients (age ≥ 45 years) with diabetes and patients without diabetes may switch to HD or receive a kidney graft in 1 – 2 years’ time; younger patients (age < 45 years) with diabetes may stay on PD longer. Use of ACEI and ARB or antioxidants can help to maintain peritoneal membrane function longer.