Beraprost sodium improves survival rates in anti-glomerular basement membrane glomerulonephritis and 5/6 nephrectomized chronic kidney disease rats

• Published in: European journal of pharmacology 2013-08, Vol.714 (1-3), p.325-331
• Main Authors: Yamaguchi, Shinichi, Inada, Chifumi, Tamura, Mitsutaka, Sato, Nahoko, Yamada, Masateru, Itaba, Shoichi, Okazaki, Seiji, Matsuura, Hirotoshi, Fujii, Shigeo, Matsuda, Fuko, Goto, Yasufumi, Mochizuki, Hidenori, Kurumatani, Hajimu, Miyamoto, Mitsuko
• Format: Article
• Language: English
• Subjects: 5/6 nephrectomized; Animals; Anti-glomerular basement membrane glomerulonephritis; Aorta - cytology; Beraprost sodium; Chronic kidney disease; Cyclic AMP - metabolism; Endothelial cell protection; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Epoprostenol - analogs & derivatives; Epoprostenol - pharmacology; Epoprostenol - therapeutic use; Glomerular Basement Membrane - drug effects; Glomerulonephritis - blood; Glomerulonephritis - drug therapy; Humans; Indican - blood; Indoxyl sulfate; Male; Nephrectomy; Rats; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - drug therapy; Renal Insufficiency, Chronic - surgery; Survival Analysis; Survival rate; Uremic toxin
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2013.07.032

Beraprost sodium, a stable prostacyclin analog, was showed to improve survival rates in two different rat models, anti-glomerular basement membrane (GBM) glomerulonephritis (GN) and 5/6 nephrectomized (Nx) chronic kidney disease (CKD) rats. In the anti-GBM rat, beraprost sodium (0.2 and 0.6mg/kg/day) improved survival rate (hazard ratio for beraprost sodium 0.6mg/kg/day group, 0.10; 95% confidence interval, 0.01 to 0.68). Subsequently, in the 5/6 Nx CKD rat, beraprost sodium (0.6mg/kg/day) improved survival rate (hazard ratio for beraprost sodium, 0.46; 95% confidence interval, 0.23 to 0.92), serum creatinine doubling time and the slope of the reciprocal of serum creatinine. In the anti-GBM GN rats, beraprost sodium suppressed the serum accumulation of representative uremic toxins such as indoxyl sulfate. Furthermore, beraprost sodium inhibited human aortic endothelial cell (HAEC) injury induced by indoxyl sulfate, indicating that beraprost sodium might have a protective effect against cardiovascular damage due to CKD. These results show that beraprost sodium can improve the survival rates in two rat models of anti-GBM GN and 5/6 Nx CKD rats by protecting endothelial cells and thereby ameliorating decreased renal function. Therefore, clinical studies are needed in patients with chronic kidney failure to determine whether beraprost sodium will become a useful medication in CKD.