73m(2). After a mean follow-up of 7-years, 104 patients had started ESRD treatment and 14 had died before reaching ESRD. The 7-year
renal survival rate was 69 for FSGS, 88 for MN, and 82 for IgAN (p < 0.01). In patients with FSGS, younger age was associated with a higher risk of ESRD. Baseline proteinuria, selleck chemical diabetes, and haemoglobin (Hb) concentration were strongly associated with shorter time to ESRD independent of baseline eGFR, but gender, hypertension and smoking were not. Adjusted HRs for ESRD were 2.6 [95% confidence interval, 1.2-5.8] for diabetes and 2.4 [1.3-4.5] for the lowest and 1.9 [1.0-3.6] for the intermediate Hb tertiles versus the highest.
Discussion: In patients with primary GN, renal survival is clearly lower for FSGS than for IgAN and MN. Independent predictors for progression were baseline diabetes and anaemia, as well as proteinuria, for all GN types, and younger
age, for FSGS.”
“Molecular mechanisms and signaling pathways leading to cellular proliferation and lesion JQ-EZ-05 clinical trial formation in the crescentic glomerulonephritis (CGN) remain elusive. In the present study we have explored a potential role of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and amino acid transporter (LAT) in the pathogenesis of CGN. Immunohistochemistry and western blot analysis of glomeruli isolated from a rat model of CGN revealed that activation of mTORC1 preceded crescent formation in glomerular parietal epithelial cells (PECs) and podocytes. Daily treatment of rats with the mTOR inhibitor everolimus just after induction of CGN was not beneficial and instead led to increased cellular necrosis of PECs. However, daily treatment starting 7 days after the onset of CGN was beneficial and maintained intact glomeruli. Out of three forms of L-type neutral amino acid transporters (LAT1-LAT3) studied here, only LAT2 was found to be upregulated in the PECs and podocytes in advance of the crescent formation as well as in the crescent lesion itself.
Cell culture study revealed that plasma membrane expression of LAT2 markedly stimulated mTORC1 signaling pathway, Dorsomorphin which was significantly abrogated by coexistence of LAT inhibitor. Finally, LAT inhibitor significantly abrogated development of crescent formation of CGN on day 7. Our data suggest that LAT2 may have a pivotal role in the pathogenesis of CGN by activating the mTORC1 pathway in the glomerular epithelial cells. Laboratory Investigation (2011) 91, 992-1006; doi:10.1038/labinvest.2011.43; published online 14 March 2011″
“Background: Increased levels of cerebrospinal fluid (CSF) 14-3-3 proteins have been reported in acute bacterial meningitis. We tested the hypothesis that CSF 14-3-3 protein levels are substantially increased in acute bacterial meningitis and decreased after anti-microbial therapy, and that CSF 14-3-3 protein levels can predict treatment outcomes.