The mesothelium is part of the peritoneal water and ion transport barrier essential for peritoneal dialysis (PD) treatment and has a central role in the pathogenesis of peritoneal fibrosis and ultrafiltration failure observed in many PD patients. We investigated the effect of amiloride on the transmesothelial electrical resistance (RTM) of isolated parietal human peritoneum. Intact sheets were obtained from seven patients (three men, four women; mean age, 64 +/- 8 years). Fourteen peritoneal planar sheets were transferred to the laboratory in oxygenated Krebs-Ringer bicarbonate solution at 4 degrees C within 30 minutes after removal and mounted in an Ussing-type chamber. Amiloride (10(-3) mol/L) added apically (n = 8) caused a rapid rise of the RTM to 24.15 +/- 0.76 [OMEGA]H cm2 and a subsequent value persistence (p < 0.05); added basolaterally (n = 6), it increased the RTM to 22.66 +/- 0.59 [OMEGA]H cm2 within 1 minute, which persisted throughout the experiment. RTM was measured before and serially for 30 minutes after addition of amiloride. Control RTM was 20.29 +/- 0.86 [OMEGA]H cm2. These results indicate a rapid inhibitory effect of amiloride on the ionic permeability of parietal human peritoneum. The increase in the RTM observed after addition of amiloride clearly indicates the existence of amiloride-sensitive sodium channels on the human parietal peritoneal membrane, which may play some role in the ultrafiltration process and sodium removal during PD.

The peritoneal mesothelium constitutes an ion transport barrier that is taken advantage of in peritoneal dialysis. The aim of this study was to investigate the effects of epinephrine on the electrical transmesothelial resistance (R(TM)) of the isolated parietal sheep peritoneum by means of Ussing-type chamber experiments. Intact parietal (diaphragmatic) peritoneal samples were obtained from adult sheep immediately after sacrifice and transferred within 0.5 h to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5), bubbled with 95% O2-5% CO2. A parietal peritoneal planar sheet was mounted in a Ussing-type chamber. Epinephrine (10(-7) M) was added to the apical and the basolateral side. The R(TM) was measured before and serially after the addition of epinephrine for 30 min. As active ion transport is temperature-dependent, all measurements were performed at 37 degrees C. The results were calculated as means with standard errors (x +/- SE) of six independent experiments. The control R(TM) was 20.05 +/- 0.61 ohm x cm2. The addition of epinephrine to the basolateral side within 1 min induced an increase of R(TM) to 21.8 +/- 0.45 ohm x cm2, which decreased thereafter progressively to reach control values again after 15 min. A similar effect of epinephrine on the apical side was apparent with a rapid rise of R(TM) to 22.5 +/- 0.66 ohm x cm2 and a subsequent decrease (P < 0.05). A clear association between the R(TM) and active ion transport was established from previous studies. The results of our study indicate a rapid action of epinephrine on the parietal peritoneum permeability.

BackgroundAlthough renal involvement in advanced haematological malignancies is common, glomerulonephritis associated with lymphoproliferative disorders is rare, and the related pathogenetic mechanisms are still poorly understood. We present a rare case of chronic lymphocytic leukaemia(CLL)-associated focal segmental glomerulosclerosis with nephrotic-range proteinuria.Case presentationA 53-year-old Caucasian man, previously healthy, with no history of hypertension, alcohol use or smoking presented with rapid weight gain, massive peripheral oedema, and hypertension. Laboratory findings included a white blood cell count of 49,800 cells/mm3 with an absolute lymphocyte count of 47,000 cells/mm3, serum albumin of 2.3 g/dL, urea 65 mg/dL, and creatinine 1.5 mg/dL. A 24-hour urine collection contained 7.1 g protein and significant haematuria. A peripheral blood smear showed mature lymphocytosis and smudge cells. Diagnostic imaging showed mild paraaortic lymphadenopathy with no renal abnormalities. Bone marrow aspiration and trephine biopsy showed diffuse and focal infiltration with B-CLL lymphocytes. Percutaneous renal biopsy revealed total sclerosis in 3/21(14%) of the glomeruli and focal and segmental solidification and sclerosis in 4/21 (19%) glomeruli. A regimen of fludarabine, cyclophosphamide and rituximab was successful in inducing remission of the CLL and clinical resolution of the nephritic-range proteinuria.ConclusionsA multidisciplinary approach to monitor both the malignancy and the glomerular lesions is crucial for the optimal management of paraneoplastic glomerulonephritis. Although chemotherapy with fludarabine, cyclophosphamide and rituximab successfully treated CLL-associated nephrotic syndrome in our patient, further studies are required to confirm efficacy in this setting.

Mesothelium is an important part of the peritoneal barrier for water and ion transport, essential for effective peritoneal dialysis (PD). Peritoneal fibrosis has been associated with PD treatment failure. Endothelin-1 (ET-1) is a potent vasoactive peptide, involved in pathologic fibrotic processes. Its action is mediated mainly by endothelin type A (ETA ) and type B (ETB ) receptors. The aim of this study was to investigate, by Ussing chamber experiments, the effect of ET-1 on the transmesothelial electrical resistance (RTM ) of the isolated visceral sheep peritoneum. Intact sheets of visceral peritoneum were obtained from 40 adult sheep and mounted in Ussing-type chambers. ET-1 (10(-7)  M), BQ-123 (ETA receptor antagonist; 10(-6)  M), BQ-788 (ETB receptor antagonist; 10(-6)  M), and their combinations were added on the apical and the basolateral side of the peritoneum. RTM was measured before and serially after addition of the substances, and changes were registered as percentage (ΔRTM %). RTM increased within 1 min after addition of ET-1 apically (ΔRTM 65.03 ± 15.87%; P < 0.05) or basolaterally (ΔRTM 85.5 ± 20.86%; P < 0.05). BQ-123 and BQ-788 and their combination significantly reduced (P < 0.05) the effect of ET-1 to a similar degree in all cases. These results clearly indicate that ET-1 reduces ionic permeability of the visceral sheep peritoneum in vitro. Additionally, it is obvious that this inhibitory effect is mediated through both ETA and ETB receptors.

In patients on chronic hemodialysis the prevalence of atherosclerosis is increased and is by far the leading cause of morbidity and mortality. Endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic effects on vascular smooth muscles, is involved in the pathogenesis of atherosclerosis. The aim of the present study was to investigate the time course of plasma endothelin-1 levels during a hemodialysis session and to explore the influence of preexisting type 2 diabetes mellitus. Forty-five clinically stable hemodialysis patients (21 females, 24 males; mean age 62 +/- 12 years) were evaluated. Patients with type 2 diabetes (n= 11) were compared with the group of patients without diabetes (n=34). Relative blood volume (BV) changes (hemoglobinometry) and blood pressure (BP) was measured. Samples were taken before, every hour during, and after hemodialysis. Plasma endothelin-1 levels were measured by enzyme-linked immunoassay (ELISA) and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration of 2215 +/- 952 mL was performed. Total BV at the end of hemodialysis was 89.3% +/- 8.3% of the pretreatment volume. Plasma endothelin-1 was enhanced in hemodialysis patients compared to normal subjects and increased from 1.28 +/- 0.47 before to 1.44 +/- 0.54 pg/mL (ref. 0.3-0.9) at the end of hemodialysis (p<0.05). The BV change (r=0.41) and the BP (mean BP: r=0.34) correlated with plasma endothelin-1 at the end of hemodialysis (p<0.05). The levels of endothelin-1 were significantly higher in the group of dialysis patients with type 2 diabetes compared to nondiabetics in all measurements (p<0.05). These findings suggest a potential role of endothelin-1 in the pathogenesis of vascular dysfunction in diabetes mellitus. The dialysis procedure per se, through vasoconstriction due to BV decrease, local endothelial injury (a.v. fistula), or bioincompatibility reactions (foreign surface contact) may additionally alter endothelial cell functions.