The immunosuppressive action of the calcineurin inhibitor cyclosporine A (CsA) stems from the inhibition of nuclear factor of activated T cells (NFAT) signaling in T cells. CsA is also used for the treatment of proteinuric kidney diseases. As it stands, the antiproteinuric effect of CsA is attributed to its immunosuppressive action. Here we show that the beneficial effect of CsA on proteinuria is not dependent on NFAT inhibition in T cells, but rather results from the stabilization of the actin cytoskeleton in kidney podocytes. CsA blocks the calcineurin-mediated dephosphorylation of synaptopodin, a regulator of Rho GTPases in podocytes, thereby preserving the phosphorylation-dependent synaptopodin–14-3-3β interaction. Preservation of this interaction, in turn, protects synaptopodin from cathepsin L–mediated degradation. These results represent a new view of calcineurin signaling and shed further light on the treatment of proteinuric kidney diseases. Novel calcineurin substrates such as synaptopodin may provide promising starting points for antiproteinuric drugs that avoid the serious side effects of long-term CsA treatment.

The actin-based foot processes of kidney podocytes and the interposed slit diaphragm form the final barrier to proteinuria. Mutations affecting several podocyte proteins cause disruption of the filtration barrier and rearrangement of the highly dynamic podocyte actin cytoskeleton. Proteins regulating the plasticity of the podocyte actin cytoskeleton are therefore of critical importance for sustained kidney barrier function. Synaptopodin is an actin-associated protein essential for the integrity of the podocyte actin cytoskeleton because synaptopodin-deficient mice display impaired recovery from protamine sulfate-induced foot process effacement and lipopolysaccharide-induced nephrotic syndrome. Moreover, bigenic heterozygosity for synaptopodin and CD2AP is sufficient to induce spontaneous proteinuria and focal segmen-

PHG was associated with portal hypertension severity and prognosis in patients with cirrhosis.

Background Long-term peritoneal dialysis (PD) is associated with the development of various structural and functional changes to the peritoneal membrane when bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this study, we looked at patients that were treated with conventional PDFs and then changed to novel biocompatible PDFs with a neutral pH and a low concentration of glucose degradation products (GDPs) to investigate whether this change could result in the arrest or reversal of peritoneal membrane deterioration. Methods In an open label, randomized prospective trial, the clinical effects of conventional PDFs and biocompatible PDFs with neutral pH and very low concentration of GDPs were compared in 104 patients equally divided between both study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests, and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The target variables were the ratio of dialysate-to-plasma (D/P) creatinine, peritoneal ultrafiltration, residual renal function, dialysis adequacy indices, and effluent cancer antigen 125 (CA125). Results D/P creatinine values were not different in the two groups. Peritoneal ultrafiltration was significantly higher in the low-GDP PDF group than in the conventional PDF group at all follow-up times (4 months: 9.1 ± 4.3 vs 6.0 ± 3.0; 8 months: 8.3 ± 3.4 vs 6.0 ± 3.0; 12 months: 8.9 ± 3.3 vs 6.1 ± 3.3 mL/g dextrose/day; p < 0.05). Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were significantly higher in the low-GDP PDF group than in the conventional PDF group. Residual renal function was not statistically significant. Effluent CA125 levels were significantly higher in the low-GDP PDF group at all follow-up visits (4 months: 37.8 ± 20.8 vs 22.0 ± 9.5; 8 months: 41.2 ± 20.3 vs 25.9 ± 11.3; 12 months: 40.4 ± 21.4 vs 28.6 ± 13.0 U/mL; p < 0.05). Among anuric patients, peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8 months, and CA125 levels at all follow-up visits were significantly higher in patients treated with low-GDP PDF than those treated with conventional PDF. However, among anuric patients, D/P creatinine showed no significant differences between the low-GDP PDF group and the conventional PDF group. Conclusion The use of biocompatible PDFs with neutral pH and low GDP concentration can contribute to improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an indicator of peritoneal membrane integrity in PD patients.

Sclerosing encapsulating peritonitis (SEP) is a rare yet serious complication in patients with continuous ambulatory peritoneal dialysis (CAPD). Incidence and prevalence of this syndrome have been defined in some large populations and a few single-centre experiences, but there is no satisfactory estimate of the comparative incidence of dialysis related SEP. The pathogenesis of SEP still remains uncertain, but there could be various causative factors. The diagnosis of SEP remains based on clinical suspicion confirmed with radiologic and/or pathologic findings. The possible variable etiologies and probable distinct pathways leading to this syndrome may make a uniform therapeutic approach unlikely. To determine the prevalence, etiologic factors, clinical features, effect of dialysis duration, and outcome of SEP in Korea, patients undergoing CAPD who developed SEP were retrospectively studied in five University Hospital dialysis centres with large numbers of CAPD patients in Korea. Out of a total 3888 CAPD studied patients between January 1981 to December 2002 in those five medical centres, 31 cases developed SEP with the overall prevalence 0.8%. There were 15 men and 16 women. The mean age of these patients was 44.0 +/- 9.8 years old. The mean duration of CAPD before SEP was 70.3 +/- 41.9 months (range 9-144 months) and 67.8% of patients (21/31) had been on CAPD more than 4 years. Peritonitis, including one fungal peritonitis, was the main cause of SEP in 25 cases (80.6%). Seventy percent of these cases used beta-blocker and the mean duration of the usage was 61.7 +/- 47.6 months. Seven cases were surgically treated and others were treated conservatively with intermittent total parenteral nutrition. The mortality rate was 25.8%. In conclusion, SEP is a serious life threatening complication of CAPD, and most cases had long-term peritoneal dialysis (PD) duration more than 4 years. To reduce the incidence of SEP, careful monitoring may be needed especially in patients with long-term CAPD and peritonitis.