The aim of the present study was to reveal the effect of a xanthine oxidoreductase (XOR) inhibitor, topiroxostat (Top), compared with another inhibitor, febuxostat (Feb), in an adenine-induced renal injury model. We used human liver-type fatty acid-binding protein (L-FABP) chromosomal transgenic mice, and urinary L-FABP, a biomarker of tubulointerstitial damage, was used to evaluate tubulointerstitial damage. Male transgenic mice (n = 24) were fed a 0.2% (wt/wt) adenine-containing diet. Two weeks after the start of this diet, renal dysfunction was confirmed, and the mice were divided into the following four groups: the adenine group was given only the diet containing adenine, and the Feb, high-dose Top (Top-H), and low-dose Top (Top-L) groups were given diets containing Feb (3 mg/kg), Top-H (3 mg/kg), and Top-L (1 mg/kg) in addition to adenine for another 2 wk. After withdrawal of the adenine diet, each medication was continued for 2 wk. Serum creatinine levels, the degree of macrophage infiltration, tubulointerstitial damage, renal fibrosis, urinary 15-F2t-isoprostane levels, and renal XOR activity were significantly attenuated in the kidneys of the Feb, Top-L, and Top-H groups compared with the adenine group. Serum creatinine levels in the Top-L and Top-H groups as well as renal XOR in the Top-H group were significantly lower than those in the Feb group. Urinary excretion of L-FABP in both the Top-H and Top-L groups was significantly lower than in the adenine and Feb groups. In conclusion, Top attenuated renal damage in an adenine-induced renal injury model.
The aim of this study was to investigate the renoprotective effect of bardoxolone methyl (BM), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator with an antioxidant effect, in a salt-sensitive hypertension model induced by aldosterone (Ald) and salt. Tubulointerstitial damage with urinary liver-type fatty acid-binding protein (L-FABP) was evaluated using human L-FABP chromosomal transgenic (L-FABP +/ − ) male mice. The mice in the Ald group (n = 7) received systemic Ald infusions via an osmotic minipump and were given 1% NaCl water for 35 days. Those in the Ald-BM group (n = 8) were administered BM intraperitoneally in addition to an injection of Ald and salt. The dose of BM was gradually increased every 7 days up to 10 mg kg − 1 per day, which was maintained for 14 days. The administration of BM significantly increased renal expression of the Nrf2 target antioxidant gene. Tubulointerstitial damage was significantly ameliorated in the Ald-BM group compared to the Ald group. The increase in reactive oxygen species (ROS) and upregulation of angiotensinogen expression in the kidneys of the Ald group was significantly prevented in the Ald-BM group. The upregulation of human L-FABP expression induced in the kidneys and increase in urinary L-FABP in the Ald group were significantly suppressed by BM administration. In conclusion, BM ameliorated tubulointerstitial damage in the Ald-and salt-induced hypertension model through suppression of both ROS production and intrarenal renin-angiotensin system activation. Urinary L-FABP may be a useful marker reflecting the therapeutic efficacy of BM.
Background: Therapeutic plasma exchange (TPE) is an important treatment modality for various diseases, but its use can be restricted by allergic reactions (AR). The aim of our study was to elucidate the frequency of and risk factors for AR at initial TPE using fresh frozen plasma (FFP).Methods: Presences of AR were extracted from the medical records of consecutive patients receiving TPE from 2002 to 2012. The following data at initial TPE were retrieved: age, gender, history of allergy, steroid use, timing of steroid use, mean steroid dose, immunosuppressant use, indication for TPE, and laboratory data.Results: Eighty-eight patients (median age 57 years) underwent TPE, and 28% had an episode of AR. Younger age (odds ratio (OR), 1.04 (95% CI, 1.01-1.08)) and indications other than hepatic insufficiency (OR, 17.8 (95% CI, 1.95-429.4)) were associated with higher incidence of AR.Conclusions: Close observation for AR may be warranted at initial TPE for these conditions.
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