title: Beraprost sodium improves survival rates in anti-glomerular basement membrane glomerulonephritis and 5/6 nephrectomized chronic kidney disease rats.
abstract: 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 0.6 mg/kg/day) improved survival rate (hazard ratio for beraprost sodium 0.6 mg/kg/day group, 0.10; 95% confidence interval, 0.01 to 0.68). Subsequently, in the 5/6 Nx CKD rat, beraprost sodium (0.6 mg/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.
authors.affiliation: Pharmacology Laboratory, Pharmaceutical Research Laboratories, Toray Industries, Inc., Kanagawa 248 8555, Japan. Shinichi_Yamaguchi@nts.toray.co.jp
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Chifumi
authors.initials: C
authors.lastname: Inada
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Tamura
authors.forename: Nahoko
authors.initials: N
authors.lastname: Sato
authors.forename: Masateru
authors.initials: M
authors.lastname: Yamada
authors.forename: Shoichi
authors.initials: S
authors.lastname: Itaba
authors.forename: Seiji
authors.initials: S
authors.lastname: Okazaki
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Matsuura
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fujii
authors.forename: Fuko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Goto
authors.forename: Hidenori
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Hajimu
authors.initials: H
authors.lastname: Kurumatani
authors.forename: Mitsuko
authors.initials: M
authors.lastname: Miyamoto
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D000242:Cyclic AMP / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D050533:Glomerular Basement Membrane / Q000187:drug effects*; D005921:Glomerulonephritis / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007200:Indican / Q000097:blood; D008297:Male; D009392:Nephrectomy; D051381:Rats; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000601:surgery*; D016019:Survival Analysis
chemical_list: C048081:beraprost; D011464:Epoprostenol; D000242:Cyclic AMP; D007200:Indican
keywords: 5/6 nephrectomized; Anti-glomerular basement membrane glomerulonephritis; Beraprost sodium; Chronic kidney disease; Endothelial cell protection; Indoxyl sulfate; Survival rate; Uremic toxin