Background: Glucose polymer is an active osmotic agent that is increasingly used as an alternative to glucose in peritoneal dialysis fluids. It was recently reported that the duration of peritoneal dialysis can be extended by using glucose polymer in patients with poor ultrafiltration. We previously demonstrated that high glucose levels damage the intercellular junctions of cultured human peritoneal mesothelial cells (HPMC), but little is known about the influence of glucose polymer. Therefore, we investigated the effects of glucose polymer on the intercellular junctions of HPMC. Methods: HPMC were isolated, cultured, and identified according to the modified method of Stylianou. M199 medium was supplemented with peritoneal dialysis solutions containing 7.5% glucose polymer or 1.5, 2.5, and 4.25% glucose. After 6 h, cell viability was assessed, intercellular junction proteins were examined by immunofluorescence techniques, and the concentration of transforming growth factor-β1 in the culture supernatant was determined. Results: Glucose significantly suppressed cell viability and significantly increased transforming growth factor-β1 production when compared with control or glucose polymer cultures. Peritoneal dialysis solutions containing 4.25% glucose caused the detachment of HPMC. Immunofluorescence of intercellular junction proteins (tight junctions: ZO-1, occludin, and claudin-1; adherens junctions: β-catenin) became weak and uneven after culture with glucose. On the other hand, glucose polymer caused little change in the immunofluorescence of these proteins when compared with control cultures. Conclusions: Glucose polymer seems to be less toxic to HPMC than glucose itself, suggesting that the glucose polymer may be better for peritoneal dialysis.

Background/Aims: Polymorphism of the endothelial nitric oxide synthase (ecNOS) gene may be involved in renal disease. Recently, T^-786→C polymorphism affecting ecNOS gene transcription has been reported. To clarify the role of T^-786→C polymorphism in renal disease, we investigated hemodialysis patients and healthy controls for this polymorphism and we compared its frequency with that of intron 4 polymorphism in the hemodialysis patients. Methods: The subjects were 252 patients who had been on hemodialysis for less than 2 years (168 with nondiabetic nephropathy and 84 with diabetic nephropathy) and 187 healthy controls. T^-786→C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism analysis. Results: The frequencies of the T/C and C/C genotypes were significantly higher in the nondiabetic hemodialysis patients than in the controls (odds ratio 1.41; 95% Cl 1.03–2.00), and were also significantly higher in the diabetic hemodialysis patients than in the controls (odds ratio 1.56; 95% Cl 1.02–2.41). In addition, T^-786→C polymorphism and intron 4 polymorphism showed strong linkage disequilibrium. Conclusion: T^-786→C polymorphism may be involved in the progression of both nondiabetic and diabetic nephropathy, along with intron 4 polymorphism.

Background Loss of peritoneal function is a major complication associated with long-term peritoneal dialysis. Observed changes include loss and degeneration of the mesothelium, submesothelial thickening, alterations in the structure and number of blood vessels, and reduplication of the vascular basement membrane. Exposure to high glucose concentrations in peritoneal dialysis solutions is known to cause injury to cultured human peritoneal mesothelial cells (HPMC) as a result of overexpression of transforming growth factor beta 1 (TGF-β1). Previous studies have demonstrated that angiotensin II (AII) increases expression of TGF-β1 in a number of different cell types; although this has not been demonstrated in HPMC. Objective To clarify possible mechanisms involved in peritoneal fibrosis, we investigated whether HPMC expressed AII-forming pathway mRNA and whether increases in AII induced by high glucose contribute to the production of TGF-β1. We also examined the effects of the angiotensin-converting enzyme inhibitor (ACEI) perindoprilat and the AII receptor blocker (ARB) candesartan on expression of TGF-β1 and proliferation of HPMC. Methods Expression of mRNA for the AII-forming pathway and TGF-β1 in HPMC was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and quantitative RT-PCR. Levels of AII and TGF-β1 following 48 hours of incubation of the cells in a range of glucose concentrations were measured by enzyme immunoassay and enzyme linked immunosorbent assay respectively. The effect of glucose on cell proliferation was examined using the water-soluble tetrazolium salt WST-1 and [3H]-thymidine uptake. We also investigated the effect of ACEI and ARB on the expression of TGF-β1 and the proliferation of HPMC incubated at high glucose for 48 hours. Results AII-forming pathway mRNA was detected in HPMC, with expression of angiotensinogen, angiotensin-converting enzyme (ACE), AII type 1 receptor, and TGF-β1 mRNA increasing following exposure to glucose according to glucose concentration. High glucose was also shown to increase the production of AII and TGF-β1 and decrease the proliferation of HPMC. In contrast, we found that both the ACEI and the ARB attenuated the increase in TGF-β1 production and reduced cell proliferation caused by exposure to high glucose. These effects were greater with a combination of the two drugs. Conclusion The present study provides evidence that ( 1 ) HPMC express mRNA for the AII-forming pathway; ( 2 ) ACEI and ARB inhibit the TGF-β1 production induced by high glucose; ( 3 ) the AII-forming pathway is one mechanism by which high glucose causes production of TGF-β1. In addition to having antihypertensive and renal-protective effects, combination therapy with an ACEI and an ARB may also be effective in preventing loss of peritoneal function and decreasing peritoneal fibrosis.

We evaluated the dose dependence of an oral adsorbent, AST-120, in 31 patients with early chronic renal failure (baseline serum creatinine: 1.2-3.0 mg/dl). Twenty-three patients were given AST-120 and eight patients were not. AST-120 was administered at three different maintenance doses, < 3.0 g, 3.0 g and 6.0 g/day, according to patients' ability to tolerate treatment. The treatment period was 12 months. The slope of the reciprocal of serum-creatinine concentration versus time was calculated to assess the progression of renal failure. This slope became significantly less steep after AST-120 treatment at 6.0 g/day, but did not change significantly at the other doses. These findings suggest that 6.0 g/day of AST-120 may delay the initiation of dialysis in patients with early chronic renal failure.

The patency rate does not differ between low-pressure dilation and high-pressure dilation.