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Background: Chronic kidney disease (CKD) is a major global problem and is also associated with a decreased health-related quality of life (HRQOL). The aim of this study was to evaluate measured HRQOL based on the new CKD classification including proteinuria stage, and the effect of measured HRQOL on CKD progression and clinical outcomes over a 3-year period. Methods: EuroQol (EQ-5D), a generic preference-based questionnaire, was administered to 537 CKD outpatients at the University of Tsukuba Hospital between November and December 2008. We evaluated disease progression in CKD patients including the incidence of end-stage kidney disease (ESKD), cardiovascular disease (CVD) and all-cause mortality over a 3-year follow-up period. Results: The proportions progressing to the higher stages were 32.6, 20.0, 36.6, 39.5, and 45.8 % from glomerular filtration rate (GFR) stages (G) 1-4, respectively. The proportion progressing to ESKD (G5D) was 0.7 % from G2, 3.9 % from G3b, 20.8 % from G4 and 63.4 % from G5. The incidence of CVD and/or death was 1.2, 4.6, 4.9, 5.3, 8.3 and 21.1 % from G1−G5, respectively. The quality-adjustment weights at G4-5 were significantly lower than at G1-2 and the weights at proteinuria stage (A) 3 were significantly lower than at A1-2. The quality-adjustment weights of patients with events such as 50 % estimated GFR decline, dialysis, CVD, and/or death were significantly lower than those without events. Conclusion: We showed CKD progression and clinical outcomes over a 3-year period. Quality-adjustment weights in CKD patients were associated with not only disease progression such as initiation of dialysis treatment and incidence of CVD events and all-cause death, but also the level of proteinuria at baseline. [ABSTRACT FROM AUTHOR]

A 29-year-old man with malignant lymphoma developed membranous nephropathy (MN) after allogeneic bone-marrow transplantation (BMT). There had been no obvious findings of graft versus host diseases (GVHD) after BMT, and the dosage of immunosuppressant drugs had not been reduced during this period. At the onset of MN, a few lymphoma cells still remained in the bone marrow; the patient achieved complete remission of MN after the disappearance of the lymphoma cells. In this case it is suggested that immune complexes including antigens expressed by lymphoma cells might induce MN. Therefore, this is a significant case that may reveal an alternative mechanism of the onset of MN related to BMT. [ABSTRACT FROM AUTHOR]

Nrf2 is a basic leucine zipper transcriptional activator that is essential for the coordinate transcriptional induction of various antioxidant drug-metabolizing enzymes. Numerous studies have firmly established Nrf2's importance in protection from oxidative stress and certain chemical insults. Given the protective function of Nrf2, surprisingly few studies have focused on the relationship between Nrf2 and apoptosis. Therefore, we analysed how Nrf2 influences Fas signaling using Nrf2-deficient T cells. At a concentration of 1?µg/ml, the anti-Fas antibody induced 60% of cell death in Nrf2-deficient cultured thymocytes while, using the same treatment, only 40% of Nrf2 wild-type thymocytes died (P<0.05). Nrf2 deficiency enhances the sensitivity of Fas-mediated apoptosis in T cells. Next we examined the effect of Nrf2 deficiency during hepatocellular apoptosis in vivo. In comparison to wild-type mice, Nrf2-deficient mice displayed more severe hepatitis after induction with the anti-Fas antibody or tumor necrosis factor (TNF)-a. The enhanced sensitivity to anti-Fas or TNF-a stimulation was restored by preadministration of glutathione ethyl monoester, a compound capable of passing the cell membrane and upregulating the intracellular levels of glutathione. The results indicated that Nrf2 activity regulates the sensitivity of death signals by means of intracellular glutathione levels.Oncogene (2003) 22, 9275-9281. doi:10.1038/sj.onc.1207024 [ABSTRACT FROM AUTHOR]

The recent development of electron paramagnetic resonance (EPR) permits its application for in vivo studies of nitric oxide (NO). In this study, we tried to obtain 3D EPR images of endogenous NO in the abdominal organs of lipopolysuccaride (LPS) treated mice. Male ICR mice, each weighing about 30 g, received 10 mg/kg of LPS intraperitoneally. Six hours later, a spin trapping reagent comprised of iron and an N-dithiocarboxy sarcosine complex (Fe(DTCS)2, Fe 200 mM, DTCS/Fe = 3) were injected subcutaneously. Two hours after this treatment, the mice were fixed in a plastic holder and set in the EPR system, equipped with a loop-gap resonator and a 1 GHz microwave. NO was detected as an NO-Fe(DTCS)2 complex, which had a characteristic 3-line EPR spectrum. NO-Fe(DTCS)2 complexes in organ homogenates were also measured using a conventional X-band EPR system. NO-Fe(DTCS)2 spectra were obtained in the upper abdominal area of LPS treated mice at 8 h after the LPS injection. 3D EPR tiled and stereoscopic images of the NO distribution in the hepatic and renal areas were obtained at the same time. The NO-Fe(DTCS)2 distribution in abdominal organs was confirmed in each organ homogenate using conventional X-band EPR. This is the first known EPR image of NO in live mice kidneys. [ABSTRACT FROM AUTHOR]