The effects of strict salt control on blood pressure and cardiac condition in end-stage renal disease: prospective-study.

INTRODUCTION: Overhydration is the main contributory factor of left ventricular hypertrophy and closely associated with cardiovascular events in end stage renal disease (ESRD) patients. The aim of this prospective-study was to investigate the impact of strict salt and volume control on hypertension and cardiac condition in ESRD patients. METHODS: A total of 12 peritoneal dialysis (PD) and 15 prevalent hemodialysis (HD) patients were enrolled. All patients either PD or HD were allocated to intervention of strict salt restriction according to basal hydration state of empty abdomen in PD and midweek predialysis HD which were estimated by body composition monitor (BCM) and echocardiography. RESULTS: Mean ages were 48.3 ± 16.7 years for PD, and 48.8 ± 18 for HD patients. Extracellular water/height was 10.04 ± 2.70 and 10.39 ± 1.53 L/m in PD and HD groups. Systolic blood pressures decreased in PD and HD from 133.1 ± 28 and 147.3 ± 28.5 to 114.8 ± 16.5 and 119.3 ± 12.1 mmHg, respectively, (p < 0.00). IDKA/DW were decreased from 3.26 ± 1.6 to 2.97 ± 1.63 % in HD group (p > 0.05). LVMI and LAI were not increased in both groups. CONCLUSION: Strict salt and volume control in ESRD patients after assessment of hydration status with either using BCM or echocardiography provides better management of volume control leading to more precise cardiovascular protection.

The effects of mycophenolate mofetil on encapsulated peritoneal sclerosis model in rats.

INTRODUCTION: Encapsulated peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis. We aimed to investigate the effects of mycophenolate mofetil (MMF) treatment in experimental EPS in rats. METHODS: 40 nonuremic Wistar albino rats were divided equally into 4 groups: control rats received 2 ml isotonic saline intraperitoneally daily for 3 weeks without any other treatment. The chlorhexidine gluconate group received intraperitoneally 2 ml/200 g injection of chlorhexidine gluconate and ethanol dissolved in saline for 3 weeks. The resting group received chlorhexidine gluconate (0 - 3rd week) + peritoneal resting (4th - 6th week). The MMF group received chlorhexidine gluconate (0 - 3rd week) + 125 mg/l MMF in drinking water (4th - 6th week). Dialysate cytokine levels, leukocyte count, peritoneal thickness, inflammation and fibroblast activities were evaluated. RESULTS: Although the MMF and resting groups showed beneficial effects on ultrafiltration and D1/D0 glucose compared to the chlorhexidine gluconate group, only MMF treatment improved dialysate TGFß1, VEGF and MCP-1 levels compared to the resting group. Inflammatory activity and vascularity observed in a tissue biopsy, including capillaries number per mm2 of submesothelial area, decreased in the treatment group. CONCLUSIONS: MMF treatment has beneficial effects on EPS via inhibiting inflammation and neovascularisation by reducing dialysate VEGF overexpression.

A novel angiogenesis inhibitor, sunitinib malate, in encapsulating peritoneal sclerosis.

INTRODUCTION: Encapsulated peritoneal sclerosis (EPS) is characterized by neoangiogenesis and fibrosis. Increased inflammation is the leading cause of EPS. In turn, neoangiogenesis is both a consequence of and contributor to inflammation. The effects of sunitinib, a multitargeted receptor tyrosine kinase inhibitor, have been postulated in various antiangiogenesis, antiinflammatory and antifibrotic processes both in vitro and in vivo. This novel angiogenesis inhibitor, Sutent (sunitinib malate), was investigated in our rat EPS model. MATERIALS AND METHODS: Forty nonuremic Wistar albino rats were divided into 4 groups as follows: 2-mL isotonic saline intraperitoneally (i.p.) daily, for 3 weeks (control group); daily 2 ml/200 g injection i.p. of chlorhexidine gluconate (0.1%) and ethanol (15%) dissolved in saline, 3 weeks (CG group); CG + additional 3 weeks without any treatment, total 6 weeks (resting group); and CG + additional 3 weeks 1 mg/kg daily Sutent (SUT) in drinking water, total 6 weeks (SUT group). At the end of the study, 1-hour PET was performed. Functional parameters and morphological changes of peritoneum with dialysate cytokine levels were examined. RESULTS: SUT renewed ultrafiltration failure, D1/D0 glucose levels and dialysate protein loss. Peritoneal thickness, white blood cell count and inflammation of peritoneum were also decreased with SUT treatment. SUT significantly improved overexpression of dialysate transforming growth factor-ß1, monocyte chemoattractant protein-1 and vascular endothelial growth factor (VEGF) levels as compared with resting group. CONCLUSION: In conclusion, SUT might preserve membrane viability even at lower dosages. Although this is an experimental study, we believe that SUT after controlled trials may be a therapeutic agent for long-term peritoneal dialysis patients.

The effects of colchicine on the progression and regression of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is an infrequent but extremely serious complication of long-term peritoneal dialysis. Fibrosis of the submesothelial compact zone and neoangiogenesis underlie the pathophysiology of EPS. Colchicine is a well-known anti-inflammatory and antifibrotic agent that has been used for some fibrosing clinical states, such as liver fibrosis. OBJECTIVE: To determine the antifibrotic and anti-inflammatory effects of colchicine in an EPS rat model in both progression (P) and regression (R). METHODS: 48 nonuremic albino Wistar rats were divided into 5 groups: control group, 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group, IP injection of 2 mL/200 g chlorhexidine gluconate (CG) (0.1%) and ethanol (15%) dissolved in saline, daily for 3 weeks; resting group, CG (0 - 3 weeks) + peritoneal resting (4 - 6 weeks); C-R group, CG (0 - 3 weeks) + 1 mg/L colchicine (4 - 6 weeks); C-P group, CG (0 - 3 weeks) + 1 mg/L colchicine in drinking water (0 - 3 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% peritoneal dialysis solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume, and morphological changes of parietal peritoneum were examined. RESULT: Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased ultrafiltration volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Resting had some beneficial effects on peritoneal derangements; however, once the peritoneum had been stimulated, resting alone was not enough to reverse these pathological changes. Colchicine had more pronounced effects on membrane integrity via decreased inflammation, cell infiltration, and vascularity compared to the resting group. CONCLUSION: We suggest that colchicine may have therapeutic value in the management of EPS.

Rosiglitazone, a peroxisome proliferator-activated receptor agonist, improves peritoneal alterations resulting from an encapsulated peritoneal sclerosis model.

Inflammation, fibrosis, and angiogenesis underlie the pathophysiology of encapsulating peritoneal sclerosis (EPS). The irreversible sclerosis of visceral and parietal peritoneum that characterizes EPS can be seen in peritoneal dialysis (PD) patients after long periods on dialysis. Peroxisome proliferator-activated receptors (PPARs) are the major regulator of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The aim of the present study was to investigate the effect of the PPAR agonist rosiglitazone on the progression and regression of peritoneal alterations in chlorhexidine gluconate-induced EPS in rats. We divided 53 nonuremic Wistar albino rats into 5 groups: control group--isotonic saline 2 mL, injected intraperitoneally (IP) daily for 3 weeks; chlorhexidine gluconate (CG) group--CG 2 mL per 200 g body weight, injected IP daily for 3 weeks; Rozi-P group--CG injection as described, plus rosiglitazone in drinking water (8 mg/L) for 3 weeks; resting group--CG injection as described during weeks 1 - 3, then peritoneal rest during weeks 4 - 6; Rozi-R group--CG injection as described during weeks 1 - 3, then rosiglitazone in drinking water (8 mg/L) during weeks 4 - 6. At the end of the study, a 1-hour peritoneal equilibration test (PET) was performed with 25 mL 3.86% glucose PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate white blood cell (WBC) count, ultrafiltration (UF) volume, and morphology change in parietal peritoneum were examined. Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume, both p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness, all p < 0.05). Peritoneal rest had some advantages in UF failure and WBC count only (both p < 0.05). However, rosiglitazone was more effective than peritoneal rest for vascularity and peritoneal thickness (p < 0.05). We suggest that the PPAR agonist rosiglitazone may have a therapeutic value in the management of EPS by inhibiting inflammation and neovascularization.