Abstract: SA-PO773
Cardio-Renal Protective Effect of the Xanthine Oxidase Inhibitor Febuxostat in the 5/6 Nephrectomy Model with Hyperuricemia
Session Information
- CKD: Mechanisms - III
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Omizo, Hiroki, Teikyo University, Tokyo, Japan
- Tamura, Yoshifuru, Teikyo University School of Medicine, Tokyo, Japan
- Yamazaki, Osamu, Teikyo University, Tokyo, Japan
- Uchida, Shunya, Teikyo University School of Medicine, Tokyo, Japan
- Fujigaki, Yoshihide, Teikyo University School of Medicine, Department of Internal Medicine, Tokyo, Japan
- Shibata, Shigeru, Teikyo University School of Medicine, Tokyo, Japan
Background
Previous studies have shown that hyperuricemia can cause cardiovascular dysfunction and chronic kidney disease progression; however, the mechanisms remain unclear. In this study, we addressed the cardio-renal protective effects of xanthine oxidase (XO) inhibition in the rat remnant kidney model with hyperuricemia (RK+HUA).
Methods
Male Sprague-Dawley rats received 5/6 nephrectomy and were fed oxonic acid, the uricase inhibitor, according to the previously described methods (Kang et al., J Am Soc Nephrol 2002; Asakawa et al. Oxid Med Cell Longev 2017). XO inhibitor febuxostat was administered orally via drinking water (30 mg/l). Blood pressure and urinary albumin excretion were monitored during the course of the experiment. At 8 weeks, heart and kidney were removed for the histological evaluation.
Results
Compared with control group, RK+HUA showed significant increase in urinary albumin excretion. However, febuxostat significantly reduced albuminuria in this model, along with the reduction in serum uric acid levels. PAS-stained kidney section revealed that febuxostat attenuated glomerular and tubulointerstitial injury, confirming the renoprotective effects of XO inhibition. There was no significant difference in blood pressure levels between RK+HUA rats and RK+HUA rats that received febuxostat. However, histopathological analysis using HE-stained cardiac sections indicated that left ventricular wall thickness was reduced by febuxostat. Furthermore, quantitative evaluation of myofiber cross-sectional areas in wheat germ agglutinin (WGA)-stained sections revealed that individual myofiber hypertrophy was significantly alleviated. In addition, cardiac fibrosis was also reduced in RK+HUA with febuxostat compared with RK+HUA rats.
Conclusion
XO is involved in the cardiac and renal injury observed in the remnant kidney model with hyperuricemia. These effects can at least in part be mediated through non-hemodynamic mechanisms.