Cysteinyl 1 receptor antagonist montelukast, does not prevent peritoneal membrane damage in experimental chronic peritoneal dialysis model in rats.

BACKGROUND/AIMS: Continuous ambulatory peritoneal dialysis (CAPD) induces structural changes in the peritoneal membrane such as fibrosis, vasculopathy and angioneogenesis with a reduction in ultrafiltration capacity. Leukotriene (LT) receptor antagonists have been found to be effective to prevent fibrosis in some nonperitoneal tissues. The aim of this study is to investigate the possible beneficial effect of montelukast, a LT receptor antagonist, on peritoneal membrane exposed to hypertonic peritoneal dialysis in uremic rats. METHODS: Of the 48 male, 5/6 nephrectomized Wistar rats 29 remained alive and were included in the study. These studied rats were divided into 3 groups: Group I (n=7) was the control group, Group II (n=8) was treated with 20 ml hypertonic PDF intraperitoneally daily and Group III was treated with montelukast and similar PDF treatment protocol. The morphological and functional changes in the peritoneal membrane as well as cytokine expression were compared between groups. RESULTS: Submesothelial thickness and the severity of the degree of hyaline vasculapathy were more prominent in group III when compared to group I. There were no significant differences between group II and other groups in terms of submesothelial thickness and the severity of the degree of hyaline vasculapathy. Increased expressions of TGF-ß and VEGF in parietal peritoneal membrane were found in group II and group III when compared to group I. The amount of TGF-ß and VEGF expression were similar in group II and group III. CONCLUSION: This study suggests that montelukast treatment does not prevent the peritoneal membrane from deleterious effects of hyperosmolar PDF in the uremic environment.

The impact of diabetes mellitus on peritoneal dialysis: the Turkey Multicenter Clinic Study.

PURPOSE: It is well established that diabetic peritoneal dialysis (PD) patients have a higher mortality rate than the other PD population. This study was designed to determine the overall predictors of survival and compared mortality and morbidity between diabetic and non-diabetic Turkish PD patients. METHODS: We conducted a multicenter retrospective study with 915 PD patients [217 had diabetes mellitus (DM)]. Serum albumin, PTH, HbA1c, co-morbid diseases, dialysis adequacy (Kt/V), and peritoneal transport characteristics as well as peritonitis episodes and ultrafiltration failure during the follow-up period were recorded. RESULTS: DM patients were older and had more co-morbidities than non-DM patients. Peritonitis rates were higher in DM patients (one episode per 35.9 patient months) compared to non-DM patients (one episode per 41.5 patient months) (p < 0.001). On Kaplan-Meier analysis, patient survival was significantly lower in DM patients with the 2-, 3- and 5-year patient survival rates of 90.8%, 87.8% and 78.2% in non-diabetics and 80.9%, 70.4% and 61.2% in diabetics, respectively. On Cox regression analysis, DM (HR 1.5, p = 0.022), age (HR 1.03, p < 0.001), baseline serum albumin (HR 0.39, p < 0.001), heart failure (HR 0.038, p = 0.038), peripheral artery disease (HR 1.83, p = 0.025) and amputation (HR 4.1, p = 0.009) at baseline were significant predictors of overall mortality. CONCLUSIONS: Patient survival is lower in diabetic compared to non-diabetic patients on PD. Peritonitis rates were also higher in diabetic PD patients. DM, older age, albumin level and cardiovascular co-morbidities are predictors of mortality.

Fibroblast growth factor-23 levels are associated with vascular calcifications in peritoneal dialysis patients.

BACKGROUND: The aim of the study was to assess the relationship between fibroblast growth factor-23 (FGF-23) and vascular calcifications (VC) in peritoneal dialysis (PD) patients. METHODS: A cross-sectional study was performed in 55 PD patients who underwent pelvic X-ray to assess for VC. Patients with and without linear calcifications were recorded. RESULTS: Fifteen patients (27.3%) had linear calcifications on pelvic X-ray. FGF-23 levels were higher in patients with VC (299.5 (30.4-2,410.0) vs. 74.4 (14.8-1,030) pg/ml, p < 0.01). Diabetic patients had lower FGF-23 values (43.2 (14.9-134.0) vs. 103.5 (14.8-2,410) pg/ml, p < 0.01). Patients with residual renal function (RRF) had lower FGF-23 levels (70.6 (14.8-513) vs. 179.5 (30.4-2,410) pg/ml, p = 0.06); however, this did not reach statistical significance. FGF-23 levels, age, creatinine, Ca, dialysis duration and HbA1c were positively correlated with VC, whereas RRF, Ca intake and ALP were negatively associated. Multivariate logistic analysis confirmed FGF-23 levels, age, dialysis duration and RRF to be associated with VC. CONCLUSIONS: FGF-23 levels are associated with VC in PD patients. Further studies are needed to clarify whether it is simply a marker or a potential factor. It may prove to be an important therapeutic target for VC management.

Role of tyrosine kinase inhibition with imatinib in an encapsulating peritoneal sclerosis rat model.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is characterized by neovascularization, increased inflammation, and interstitial fibrosis of the peritoneum. We investigated the effects of imatinib on the peritoneal membrane in an experimental EPS model. METHODS: We separated 24 non-uremic Wistar rats into four groups: the control group which was injected with 2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks, the CG group which was injected with chlorhexidine gluconate (CG) IP daily for 3 weeks, the resting group which was injected with CG IP between weeks 0-3 followed by a peritoneal rest period between weeks 3-6, and the CG + Imatinib mesylate group (CG + IMA) which received CG through weeks 0-3 followed by 50 mg/kg imatinib mesylate through weeks 3-6. At the end of the study, we performed a 1-h-peritoneal equilibration test and examined the peritoneal function and transforming growth factor-ß1 (TGF-ß1) in dialysate. Morphologic changes were evaluated by microscopy and immunohistochemistry. RESULTS: An increased ultrafiltration, dialysate/plasma-creatinine-ratio, end-to-initial-dialysate-glucose-ratio, decreased active mesothelial cell ratio and inflammation, and a slightly decreased TGF-ß1 of dialysate were found in the CG + IMA group compared to CG alone. Furthermore, the CG + IMA group had a lower concentration of active mesothelial cells than did the resting group. Ultrafiltration was improved in CG + IMA group compared to resting group, however, significant decrease in peritoneal thickness and inflammation were not found compared to those in resting group. Furthermore, there was no significant difference in fibrosis or TGF-ß1-positivity on immunohistochemistry between the groups. CONCLUSIONS: Tyrosine kinase inhibition with imatinib may lead to a decrease in mesothelial cell activity and an increase in ultrafiltration. However, peritoneal fibrosis was unchanged by imatinib in EPS model.

Effects of rapamycin and tacrolimus on mature endothelial cells and endothelial progenitor cells.

OBJECTIVE: To investigate the effects of the potent immunosuppressive agents tacrolimus and rapamycin on the number of circulating mature endothelial cells and circulating endothelial progenitor cells in an experimental model. METHODS: It was an experimental study performed from December 2007 to January 2008 in which the effects of the immunosuppressive agents tacrolimus and rapamycin on endothelial progenitr cells and circulating mature endothelial cells were analysed on 24 male wistar albino rats in a controlled environment model. Circulating cell populations were measured by flow-cytometric analysis. Maun-Whitney U test and analysis of vartiance were used for statistical purposes. RESULTS: Rapamycin increased the number of circulating mature endothelial cells approximately 2-fold compared to tacrolimus. The number of endothelial progenitor cells also was increased in the peripheral blood of rats treated with rapamycin compared to those treated with tacrolimus. CONCLUSION: The study showed that treatment with rapamycin is associated with an increase in endothelial progenitor cells and circulating mature endothelial cells. This increase may be associated with endothelial cell damage and repair.

Protective effect of the vasopressin agonist terlipressin in a rat model of contrast-induced nephropathy.

BACKGROUND/AIMS: Contrast-induced nephropathy (CIN) remains a leading cause of iatrogenic acute renal failure. Terlipressin, a long-acting analog of vasopressin, may improve renal function. This study aimed to investigate the possible protective effect of terlipressin against the development of experimental CIN in rats. METHODS: Wistar albino rats (n = 32) were allocated randomly into four equal groups of 8 each, i.e. control, terlipressin, contrast media (CM), and terlipressin plus contrast media (TCM). CIN was induced by intravenous administration of indomethacin (10 mg/kg), N-nitro L-arginine methyl ester (L-NAME, 10 mg/kg, twice at 15 and 30 min), and high-osmolar contrast media meglumine amidotrizoate 60%. Renal function parameters, kidney histology, and tubular expression of vascular endothelial growth factor (VEGF) were determined. RESULTS: Mean serum creatinine levels were decreased (p < 0.05) and creatinine clearance (p < 0.05) increased in the TCM group compared with the CM group. Notably, rats in the TCM group displayed less tubular necrosis (p < 0.05), medullary congestion (p < 0.05), and a reduced tubular expression of VEGF (p < 0.05) compared with the CM group. CONCLUSION: These results demonstrate that terlipressin can inhibit the development of CIN.

Unusual causes of peritonitis in a peritoneal dialysis patient: Alcaligenes faecalis and Pantoea agglomerans.

An 87 -year-old female who was undergoing peritoneal dialysis presented with peritonitis caused by Alcaligenes faecalis and Pantoea agglomerans in consecutive years. With the following report we discuss the importance of these unusual microorganisms in peritoneal dialysis patients.

Baseline carotid intima-media thickness is associated with cardiovascular morbidity and mortality in peritoneal dialysis patients.

Carotid intima-media thickness (CIMT) is an early marker of atherosclerosis and is increased in peritoneal dialysis (PD) patients. Association of CIMT with cardiovascular disease (CVD) or mortality is less clear. Fibroblast growth factor-23 (FGF-23) is a hormone associated with vascular calcification, atherosclerosis, and mortality in the hemodialysis population. We investigated whether baseline CIMT and FGF-23 are associated with CVD and mortality in PD patients. Fifty-five PD patients were included. CVD was defined as ischemic heart disease, stroke, or peripheral artery disease. Intact FGF-23 was measured in plasma. CIMT was measured by ultrasonography. Twenty-one patients developed CVD and 12 died over 47.1 ± 33.8 months. Patients with CVD were older (55.9 ± 10.5 vs. 42.5 ± 12.9 years, P < .01), had lower albumin (3.8 ± 0.5 vs. 4.2 ± 0.3 g/dL, P < .01) and higher CIMT (0.87 ± 0.22 vs. 0.61 ± 0.11 mm, P < .01). Patients with mortality were also older (53.5 ± 11.5 vs. 45.8 ± 13.8 years, P = .05), had lower albumin (3.7 ± 0.6 vs. 4.1 ± 0.3 g/dL, P < .01), higher CRP (15.0 ± 8.5 vs. 7.6 ± 8.4 mg/L, P < .01) and CIMT (0.9 ± 0.3 vs. 0.6 ± 0.1 mm, P < .01). Albumin and CIMT were associated with CVD and CIMT > 0.75 mm was associated with cardiovascular mortality. FGF-23 did not show any correlations. CIMT at baseline is associated with CVD and mortality in PD patients.

Histopathological changes and tumour necrosis factor-alpha, transforming growth factor-beta and tenascin expression in patients with primary type I membranoproliferative glomerulonephritis in remission.

AIM: Primary type I membranoproliferative glomerulonephritis (MPGN) is a rare cause of glomerular disease with a high relapse rate and poor prognosis. The aim of this study was: (i) to evaluate the histopathological findings associated with remission; and (ii) to document the possible clinical and histopathological factors predicting relapses. METHODS: Eleven type I MPGN patients (five men, six women; mean age, 38.8+/-13.5 years) who were in remission for at least 1 year after the cessation of immunosuppressive drugs were re-biopsied. The intensity of immunostaining for tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and tenascin was graded from 0 (no staining) to 3+ (maximum staining). RESULTS: Mean baseline mesangial cellularity score and tubulointerstitial infiltration score were reduced and mesangial matrix expansion score was increased at protocol re-biopsies compared to baseline. The glomerular and tubulointerstitial staining scores for TGF-beta1 and tenascin were higher than that of baseline. Reduced tubulointerstitial TNF-alpha expression was found in re-biopsy specimens compared to baseline. Patients have been followed for a mean time of 51.5+/-22.2 months after the protocol biopsy. Eight patients had a relapse. Mesangial cellularity score and glomerular tenascin expression at re-biopsy specimens were higher in relapsed patients compared to those without a relapse. CONCLUSION: Our study shows that mesangial cellularity and tubulointerstitial cell infiltration are reducing whereas mesangial matrix expansion, glomerular and tubulointerstitial TGF-beta1 and tenascin expression are increasing with remission. The higher mesangial cell proliferation and glomerular tenascin scores in remission are associated with the development of relapse.