A case of encapsulating peritoneal sclerosis at the clinical early stage with high concentration of matrix metalloproteinase-2 in peritoneal effluent.

In encapsulating peritoneal sclerosis (EPS), matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases are involved in the remodeling of peritoneal tissue. We measured the MMP-2 concentration in the peritoneal effluents of a patient with EPS who discontinued continuous ambulatory peritoneal dialysis (CAPD) therapy because of ultrafiltration failure and/or underdialysis. First, we report a 58-year-old female patient who discontinued CAPD therapy because of underdialysis. Several months after cessation of CAPD, she complained of slightly blood-colored ascites and had an elevated level of C-reactive protein (CRP) in plasma. She was diagnosed as having clinical early-stage EPS. Peritoneal effluents drained from this case, and from 11 patients who discontinued CAPD therapy because of ultrafiltration failure and/or underdialysis, and who underwent peritoneal lavage with 1.5% dextrose peritoneal dialysis fluid for several months, were analyzed by gelatin zymography. MMP-2 concentration was also measured by enzyme-linked immunosorbent assay (ELISA). MMP-2 concentration in peritoneal effluent of this patient was highest compared with that of the other patients. There was some tendency of a positive correlation between MMP-2 concentration per 1 g protein and D/Pcr, and was negative correlation between MMP-2 concentration per 1 g of protein and D/D0 glucose. We concluded that MMP-2 is involved in the peritoneal remodeling of long-term CAPD therapy and the progression of EPS.

Multimeric vitronectin in ascites is involved in fibroblast spreading of EPS in patients on CAPD therapy.

BACKGROUND: Although encapsulating peritoneal sclerosis (EPS) is a serious complication of continuous ambulatory peritoneal dialysis (CAPD) therapy, the mechanism of the fibroneogenesis in EPS remains unknown. Because fibroblast adhesion and spreading to the extracellular matrix is the first step in peritoneal fibrosis, we investigated fibroblast spreading factor in ascites obtained from patients with EPS (EPS ascites). METHODS: To analyze fibroblast spreading activity, various concentrations of EPS ascites obtained from two EPS patients were coated on culture plates, and then the number of human fibroblasts (TIG-3) that had spread was counted. Each fraction of gel-filtered EPS ascites was also analyzed by this activity. Next, we examined the effect of the addition of Arg-Gly-Asp (RGD) peptides, several antibodies against adhesion molecules, and heparin on the fibroblast spreading activity in the EPS ascites. RESULTS: The fibroblast spreading activity of EPS ascites was about four times greater than that in ascites from a patient with nephrotic syndrome. Two major peaks (peak I and II) of spread cells were obtained when ascites were gel-filtered. The fibroblast spreading activities of the two peaks were abolished by the addition of RGD peptides and polyclonal antibody against vitronectin (VN). Immunoblotting analysis revealed that the two peaks contained VN and that peak I contained multimeric VN. Heparin, at 10 microg/ml, augmented the fibroblast spreading activity of peak I to about three times greater than the control. CONCLUSIONS: The results indicate that multimeric VN in EPS ascites plays a potential role in peritoneal fibrogenesis in EPS and that heparin may participate in peritoneal fibrosis in EPS.

Ascites from patients with encapsulating peritoneal sclerosis augments NIH/3T3 fibroblast proliferation.

Encapsulating peritoneal sclerosis (EPS) remains one of the major causes of dropout in continuous ambulatory peritoneal dialysis by reducing ultrafiltration capacity. To demonstrate whether ascites from patients with EPS (EPS ascites) has fibroblast proliferation activity, we used NIH/3T3 fibroblasts to examine the effects of EPS ascites on fibroblast proliferation activity by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Encapsulating peritoneal sclerosis ascites dose-dependently augmented NIH/3T3 fibroblast proliferation. The protein kinase C inhibitors and the tyrosine kinase inhibitors partially inhibited the stimulatory effects of EPS ascites on fibroblast proliferation activity. In EPS ascites, levels of interleukin (IL)-1beta, IL-6, IL-8, transforming growth factor (TGF)-beta1, hepatocyte growth factor (HGF), and platelet-derived growth factor (PDGF)-AB were elevated. The treatment with IL-1beta, HGF, TGF-beta1, and PDGF-AB alone or in combination at similar concentrations to those in EPS ascites exhibited small but significant fibroblast proliferation activities. We conclude that EPS ascites stimulate NIH/3T3 fibroblast proliferation via protein kinase C and tyrosine kinase. The elevated cytokine and growth factors partly contribute to the EPS ascites-induced fibroblast proliferation.

Changes in peritoneal coagulation and fibrinolysis after discontinuation of chronic peritoneal dialysis.

OBJECTIVES: To study changes in peritoneal function after transfer from chronic peritoneal dialysis (CPD) to hemodialysis (HD), especially the effects on peritoneal coagulation, fibrinolytic markers, and mesothelium. DESIGN: Prospective observational study. SETTING: A tertiary-care university hospital. PATIENTS: Nine patients who transferred from CPD to HD were enrolled in the study after giving fully informed consent. METHODS: After transfer to HD, the peritoneal cavity was lavaged with low glucose PD solution once per day through PD catheters left in place. Thrombin-antithrombin III complex (TAT) was measured serially as a marker of peritoneal coagulation. As fibrinolytic markers, fibrinogen/fibrin degradation products (FDP) and plasmin-alpha2-antiplasmin complex (PIC) were assessed. Cancer antigen 125 (CA125) was measured as a marker of mesothelial cell mass. RESULTS: Levels of peritoneal TAT and FDP were much higher than plasma levels, indicating high local fibrin turnover. Transfer to HD induced a significant fall in mean peritoneal TAT, from 115.8 +/- 52.1 to 60.7 +/- 21.8 ng/mL, p < 0.05. Except for 1 patient with a 20-fold increase, mean peritoneal FDP decreased significantly, from 43.6 +/- 11.1 to 19.6 +/- 3.5 microg/mL, p < 0.05. Mean peritoneal PIC increased significantly, from 1.9 +/- 0.4 to 3.9 +/- 0.6 microg/mL, p < 0.05. Peritoneal CA125 increased from 156.4 +/- 57.3 to 1426.2 +/- 389.4 U/mL, p < 0.05. CONCLUSIONS: Peritoneal fibrin turnover was accelerated on CPD and stabilized after transfer to HD. Transfer to HD also induced mesothelial regeneration.

Rapid and persistent reduction of proteinuria following plasma exchange in a case of steroid-resistant focal segmental glomerulosclerosis.

We report on the case of a 45 year old male with focal segmental glomerulosclerosis (FSGS) in whom steroid-resistant proteinuria was reduced rapidly by plasma exchange. In 1994, he was admitted to our hospital because of massive proteinuria of several years' duration. Renal biopsy confirmed the diagnosis of FSGS. Proteinuria was suppressed partially with the use of dipyridamole. Though oral prednisolone (PSL, 30 mg/day) was effective initially, relapse occurred during PSL tapering. Doses of PSL up to 30 mg/day or additional mizoribine were ineffective. The patient was readmitted for a trial of plasma exchange in April 2000. Four sessions of plasma exchange with albumin replacement over 2 weeks immediately reduced the proteinuria from 3.2 g/day to 0.6 g/day without any change in medication. After discharge, proteinuria remained suppressed for more than 6 months despite a reduction of PSL dose to 15 mg. The rapid and long lasting effect of plasma exchange in the present case argues for the role of a putative circulatory factor in the pathogenesis of proteinuria in FSGS.