Atorvastatin Decreases Renal Calcium Oxalate Stone Deposits by Enhancing Renal Osteopontin Expression in Hyperoxaluric Stone-Forming Rats Fed a High-Fat Diet

Abstract

Calcium oxalate (CaOx) is the major constituent of kidney stones. Growing evidence shows a close connection between hyperlipidemia, cardiovascular disease (CVD), and the formation of kidney stones. Owing to their antioxidant properties, statins control hyperlipidemia and may ameliorate CaOx stone formation. The present study was designed to investigate the suppressive effects of statins on CaOx urolithiasis and their potential mechanism. We used rats fed a high-fat diet (HFD) to achieve hyperlipidemia (HL) and hydroxyproline (HP) water to establish a hyperoxaluric CaOx nephrolithiasis model; the animals were administered statins (A) for 28 days. The rats were divided into eight groups treated or not with A, i.e., Control, HP, HL, HL + HP. HL aggravated urinary calcium crystallization compared to the control. Due to increased expression of renal osteopontin (OPN), a key anti-lithic protein, and reduced free radical production, the calcium crystals in the urinary bladder increased as renal calcium deposition decreased. The levels of the ion activity product of CaOx (AP(CaOx)) decreased after statins administration, and AP(Calcium phosphate) (CaP) increased, which suggested the dominant calcium crystal composition changed from CaOx to CaP after statin administration. In conclusion, atorvastatin decreases renal CaOx stone deposits by restoring OPN expression in hyperoxaluric rats fed a HFD.

Keywords

• atorvastatin
• calcium oxalate
• urolithiasis
• atherosclerosis
• hydroxyproline
• hyperlipidemia