Activation of interstitial myofibroblasts and excessive production of extracellular matrix proteins are common pathways that contribute to chronic kidney disease. In a number of tissues, AMP-activated kinase (AMPK) activation has been shown to inhibit fibrosis. Here, we examined the inhibitory effect of the AMPK activator, 5-aminoimidazole-4-carboxyamide ribonucleoside (AICAR), on renal fibrosis in vivo and TGF-β1-induced renal fibroblasts activation in vitro. A unilateral ureteral obstruction (UUO) model was induced in male BALB/c mice. Mice with UUO were administered AICAR (500 mg/Kg/day) or saline intraperitoneally 1 day before UUO surgery and daily thereafter. Both kidneys were harvested 7 days after surgery for further analysis. For the in vitro studies, NRK-49F rat fibroblasts were pre-incubated with AICAR before TGF-β1 stimulation. The inhibitory effects of AICAR on signaling pathways down-stream of TGF-β1 were analyzed. In UUO model mice, administration of AICAR attenuated extracellular matrix protein deposition and the expression of α-smooth muscle actin (α-SMA), type I collagen and fibronectin. Pre-incubation of NRK-49F cells with AICAR inhibited TGF-β1-induced myofibroblast activation. Silencing of AMPKα1 by siRNA or by blocking AMPK activation with Compound C diminished the inhibitory effect of AICAR. Moreover, the inhibitory effects of AICAR on TGF-β1-mediated myofibroblast activation were associated with down-regulation of ERK 1/2 and STAT3. Our results suggest that AICAR reduces tubulointerstitial fibrosis in UUO mice and inhibits TGF-β1-induced kidney myofibroblast activation. AMPK activation by AICAR may have therapeutic potential for the treatment of renal tubulointerstitial fibrosis.

Inflammatory polyneuropathies represent an important group of neurological disorders. Review of the literature disclosed that glomerulonephritis seems to be not uncommon in acute inflammatory demyelinating polyneuropathy. On the other hand, glomerulonephritis associated with chronic inflammatory demyelinating polyneuropathy (CIDP) appears to be rare. We herein report a 60-year-old man with a clinical history, physical examination and laboratory investigations consistent with CIDP, who also had severe lower limb edema and proteinuria resistant to medical therapy. Renal biopsy showed features consistent with membranous glomerulonephritis. We review the related literature, and the immunological implications are discussed.

Peritonitis is a serious complication in peritoneal dialysis (PD) patients; however, the clinical outcome of culture-negative peritonitis (CNP) is controversial. This retrospective study of CNP attempts to resolve this controversy. In 813 episodes of peritonitis, 202 episodes of CNP in 152 PD patients were reviewed. Two different methods of effluent culture were utilized during the study period. The incidence of CNP was lower with 50 ml centrifugation culture than 10 ml direct inoculation culture (20.7% vs. 35.7%; p < 0.05). The overall cure rate of CNP was greater than 80% of patients receiving cefamezine and gentamicin as initial therapy. Relapse within 30 days after completion of treatment happened in 9.6% of cases, and antibiotic therapy failed in 8.1% of CNP cases. In comparison with cured patients, patients with relapse or treatment failure are older (62.0 ± 15.0 years vs. 54.3 ± 15.3 years; p = 0.007) and have a higher rate of abdominal pain (91.4% vs. 69.3%; p = 0.007) and greater need for salvage therapy (54.3 % vs. 11.0%; p < 0.001). A history of antibiotic use or peritonitis within 30 days before onset of CNP was noted in 23.3% and 12.5% of cases, respectively, but was not associated with clinical outcome. The clinical outcome of CNP was benign in this study. Older age, abdominal pain, and need for salvage therapy were associated with an increased risk for relapse and treatment failure in CNP cases. Moreover, 50 ml centrifugation culture method was better than 10 ml direct inoculation culture in reducing the incidence of CNP.

Leptospira santarosai serovar Shermani is the most frequently encountered serovar, and it causes leptospirosis and tubulointerstitial nephritis in Taiwan. This study aims to complete the genome seq...

Dietary leucine supplementation has been explored for the therapeutic intervention of obesity and obesity-induced metabolic dysfunctions. In this study, we aim to examine the effects of dietary leucine supplementation in db/db mice. Mice were treated with or without leucine (1.5% w/v) in drinking water for 12 weeks. The leucine supplement was found to reduce insulin resistance and hepatic steatosis in db/db mice. Using Nuclear Magnetic Resonance (NMR)-based lipidomics, we found that the reduction of hepatic triglyceride synthesis was correlated with attenuated development of fatty liver. In addition, diabetic nephropathy (DN) was also ameliorated by leucine. Using liquid chromatography–time-of-flight mass spectrometry (LC-TOF MS)-based urine metabolomics analysis, we found that the disturbance of the tricarboxylic acid (TCA) cycle was reversed by leucine. The beneficial effects of leucine were probably due to AMP-activated protein kinase (AMPK) activation in the liver and kidneys of db/db mice. Thus, dietary leucine supplementation may potentially be a nutritional intervention to attenuate hepatic steatosis and early DN in type II diabetes.