Pioglitazone reduces peritoneal fibrosis via inhibition of TGF-ß, MMP-2, and MMP-9 in a model of encapsulating peritoneal sclerosis.

OBJECTIVE: Matrix metalloproteinases (MMPs) and transforming growth factor beta (TGF-ß) were increased in peritoneal dialysis patients with encapsulating peritoneal sclerosis (EPS) and in chlorhexidine gluconate (CG)-induced peritoneal sclerosing animal models. Peroxisome proliferator-activated receptors (PPARs) are the major regulators of key metabolic pathways of various inflammatory responses in fibrosing processes in most tissues. The objective of this study was to investigate the effect of pioglitazone (Pio), a synthetic PPAR-γ ligand, on the development of peritoneal fibrosis in CG-induced EPS rats. METHODS: Thirty-two Wistar albino rats were intraperitoneally injected with saline (C group n = 8) or with CG (1.5 mL/100 g; CG group, n = 8). Pio (30 mg/kg/day) was administered orally to another group of CG injected rats (the CG + Pio group, n = 8) and to another control group (Pio group, n = 8) from initiation to the end of this study. After 14 days of Pio administration, the rats were killed and the parietal and visceral peritoneum were harvested. TGF-ß, MMP-2, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 activity assays and a morphological examination of the peritoneal tissues were performed. RESULTS: Pio significantly inhibited thickening of the submesothelial layer, fibrosis, and inflammation in the peritoneum. It also prevented increases in pro-MMP-2, pro-MMP-9, TIMP-1, and TGF-ß activities. CONCLUSION: Pio, via MMP and TGF-ß inhibition, may lessen accumulation of peritoneal extracellular matrix and fibrosis to some extent in an EPS model and might be a new approach to the amelioration of EPS.

Decrease in cell proliferation by an matrix metalloproteinase inhibitor, doxycycline, in a model of immune-complex nephritis.

AIM: Renal expression of matrix metalloproteinases (MMP) and tissue inhibitors of MMP (TIMP) contribute to the development of tubulointerstitial fibrosis characteristic of progressive forms of primary glomerulonephritis (GN). The aim of this study was to investigate the therapeutic effect of MMP inhibitor, doxycycline, administration in an experimental rat model of immune-complex nephritis (ICN). METHODS: The induction of immune-complex glomerulonephritis was carried out by the administration of an i.v. dose of 2 mg bovine serum albumin (BSA) daily for 28 days after 8 weeks of s.c. immunization with 1 mg of BSA in complete Freund's adjuvant. Doxycycline (30 mg/kg) was given daily (in groups 2 and 4) by gavage for 28 days. RESULTS: Animals treated with doxycycline showed significant reduction in glomerular area and cell proliferation than non-treated controls. Glomerular deposition of immunoglobulin (Ig)G and C3 was less intense in treated rats than non-treated controls. Although not statistically significant, interstitial inflammation was less intense in treated rats than non-treated controls. Glomerular expression of MMP-9 by immunoflourescence was significantly inhibited in the treated group. In addition pro-MMP-2 on gelatin zymography was importantly suppressed by doxycycline in ICN. CONCLUSION: Doxycycline, in addition to its antibiotic property, may, following further investigation, provide a possible survival benefit in proliferative glomerulonephritis.

Effect of once-a-week vs thrice-a-week application of mupirocin on methicillin and mupirocin resistance in peritoneal dialysis patients: three years of experience.

INTRODUCTION: The application of mupirocin to the exit-site in peritoneal dialysis (PD) patients decreases peritonitis and exit-site infection (ESI) considerably. However, long-term application of mupirocin may result in the development of methicillin- and mupirocin-resistant strains. In this study, we aimed to investigate the effect of once-a-week vs. thrice-a-week application of mupirocin on mupirocin and methicillin resistance in PD patients. PATIENTS AND METHODS: Thirty-six patients were divided into two groups based on frequency of weekly mupirocin application at the catheter exit-site. In group 1, patients were randomly assigned to apply mupirocin once a week (n = 18), while patients in group 2 applied mupirocin three times a week (n = 18). We obtained cultures from the nares, inguinal area, axillae, and the exit site. The microorganisms reproduced, and the resistance to mupirocin and methicillin were recorded. Three years of follow-up of these patients were also recorded. RESULTS: During the three-year follow-up period, seven episodes (0.26 episodes/patient-years) of ESI and 13 episodes (0.36 episodes/patient-years) of peritonitis were determined in group 1, and one episode of ESI (0.11 episodes/patient-years) and six episodes (0.24 episodes/patient-years) of peritonitis were determined in group 2. The rate of peritonitis and ESI were, respectively, 56% and 92% lower in group 2 when compared to group I (p = 0.041 and p = 0.038, respectively). Throughout three years, a total of 1852 samples were analyzed. In group 1, S. aureus reproduction rate and mupirocin resistance were 2.11% and 0.2%, respectively. In group 2, S. aureus reproduction rate was 0.93%, and no mupirocin resistance was observed. Methicillin-resistant S. aureus was not observed in both groups. Coagulase-negative staphylococcus (CNS) reproduction rate was 70.56% (mupirocin resistance: 59.87% and methicillin resistance: 33.7%) and 72.56% (mupirocin resistance: 64.7% and methicillin resistance: 33.3%) in groups 1 and 2, respectively. No peritonitis and ESI secondary to S. aureus and fungal agents were observed in both groups. CONCLUSION: The thrice-a-week application of mupirocin seems to be more efficient when compared to once-a-week application of mupirocin. Long-term application of mupirocin may cause the development of mupirocin- and methicillin-resistant strains, especially in CNS, which results in a difficulty for struggling against infections.

Cytomegalovirus disease in renal transplant recipients: a single-center experience.

UNLABELLED: Cytomegalovirus (CMV) disease is an important complication and an independent risk factor for acute rejection and recipient morbidity-mortality. The aim of this study was to review the results of CMV disease in renal transplant recipients. METHOD: We have retrospectively analyzed CMV disease in 120 renal transplant recipients and recorded the demographic features, clinical manifestations, and immunosuppressive regimens. RESULTS: Twenty-nine recipients (24.1%) developed CMV disease after a median interval of 2.8 +/- 2,6 months from transplantation. CMV disease developed in 36.3% of recipients who received basiliximab as induction therapy and 21.4% of recipients who were treated with anti-thymocyte globulin (ATG). The most commonly used immunosuppressive regimen was cyclosporine-A (CsA)-based (79.3%). The mean cumulative steroid dose until the diagnosis was 3,600 mg methyl prednisolone per patient. Malaise, fever, and diarrhea were the most common symptoms. Gastritis, pneumonia, and transaminitis were the most commonly seen end-organ involvements. Frequent laboratory findings were leukopenia (34.5%), increased serum creatinine level (34.5%), and leukocytosis (20.7%). We performed renal biopsy to seven patients and detected acute rejection in four patients. In 25 patients, immunosuppressive treatment was modified. Relapsing CMV disease was seen in seven patients. CONCLUSION: In our study, CMV disease was seen in recipients who were treated with basiliximab, a finding similar to recipients who were treated with ATG.

The effect of renal replacement therapies on serum gastrointestinal system hormones.

BACKGROUND: The kidney is a major site for the inactivation, degradation, and clearance of a variety of peptide hormones. It has been shown that the uremia increases or decreases gastrointestinal system (GIS) hormones. Moreover, studies investigating the serum GIS hormones levels in chronic renal failure (CRF) were conducted mainly in a particular period of the renal replacement therapy, and the changes caused by continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) could not be fully demonstrated. In this study, we investigated the effect of CAPD and HD on serum GIS hormones (amylase, lipase, trypsinogen, and gastrin) levels in CRF patients who were diagnosed for the first time. METHODS: Serum amylase, lipase, trypsinogen, and gastrin levels were measured in 36 patients who were just diagnosed with CRF, 22 patients with CAPD and 14 patients with HD. GIS hormones of these patients were measured before treatment and three months from the beginning of CAPD and HD treatment. As the control group, 20 normal healthy cases with well-matched age and gender were used. RESULTS: The mean serum amylase, lipase, secretin, and gastrin levels were found meaningfully decreased according to the beginning values at third months of the CAPD and HD treatment. However, they were higher than control group. CONCLUSION: In patients receiving CAPD or HD as renal replacement therapy, GIS hormone levels were found to be lower, albeit higher than the healthy control group.

Effect of intravenous iron sucrose on oxidative stress in peritoneal dialysis patients.

AIM: Intravenous iron therapy is an accepted treatment for patients receiving hemodialysis and continuous ambulatory peritoneal dialysis (CAPD). Studies have found enhanced oxidative stress in hemodialysis patients receiving intravenous iron, but there are no clinical data for CAPD patients. The aim of the current study was to investigate the effect of 100 mg of intravenous iron-sucrose on the erythrocyte (RBC) antioxidant enzymes (namely, superoxide dismutase [SOD], catalase [CAT], and glutathione peroxidase [GSHPx]) and plasma malondialdehyde (MDA), an oxidant molecule, in CAPD patients. METHODS: Twelve CAPD patients receiving maintenance intravenous iron-sucrose were recruited. After a 12-hour fast, blood samples were taken for hemoglobin, iron, ferritin, and high-sensitivity C-reactive protein (hsCRP), and for baseline activities of erythrocyte antioxidant enzymes (i.e., SOD, CAT, GSHPx) and the plasma oxidant molecule, MDA. 100 mg iron-sucrose was infused over 30 minutes. Blood samples taken during (i.e., 15 minutes after commencement of infusion) and after (i.e., at 30 minutes, 60 minutes, and 6 hours after commencement) the infusion were taken for measurement of plasma iron, ferritin, TSAT, RBC SOD, CAT, GSHPx, and plasma MDA. RESULTS: Plasma iron and transferrin saturation elevated significantly during infusion (p < 0.05). There was no significant change in erythrocyte SOD, CAT, GSHPx, or in MDA activities. There was a reduction of GSHPx activity at the 30th minute (from 153.69 +/- 66.69 to 123.68 +/- 25.50 mU/mL), but it was not statistically significant. The patients were grouped according to baseline ferritin (100-400 and 400-800 ng/mL); 60th-minute MDA was significantly higher in the latter group (p < 0.05). There was no correlation between hsCRP and oxidant-antioxidant balance. No correlation was noted between RBC antioxidant enzymes or plasma oxidant molecule and ferritin levels. CONCLUSION: There are no acute deteriorating effects from a 100 mg of intravenous iron-sucrose in CAPD patients with optimal iron stores. This dose may be applied safely in CAPD patients.

Successful reuse of a transplanted kidney: 3-year follow-up.

The number of new transplantations has not kept pace with the ever-growing number of patients waiting for a kidney transplant, and there has been a growing shortage of deceased donor kidneys. Previously transplanted organs have been used to increase the donor pool. There is very little data about the reuse of a transplanted kidney. We report a case of successful reuse of a kidney graft after the death of the first recipient with a 3-year follow-up.