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To examine the dynamic changes in the formative factors of nephrolithiasis and the final micromorphological changes in an obesity-initiated metabolic syndrome (MS) rat model. Forty five-week-old male Sprague–Dawley (SD) rats were randomly divided into four groups: the regular diet group (RD), high-fat diet group (HFD), regular diet with drug (ethylene glycol and ammonium chloride) group (RDD), and high-fat diet with drug group (HFDD). A dynamic assessment of MS components (body weight (BW), body length (BL), Lee’s index (LI), blood glucose (BG), total cholesterol (TC), and triglycerides (TGs)) and stone-forming factors (urinary pH, urinary calcium, and urinary oxalate acid) was carried out. In addition, the levels of oxidative stress (OS) markers (CAT, SOD, TAC, GSH-PX, and MDA) were measured, and histological analysis was carried out at the end of 16 weeks. MS-related parameters, such as BW, LI, BG, TC, and TG, were significantly higher in HFD-fed rats than in RD-fed rats ( p  &lt; 0.001). In the HFDD group, significantly lower urinary pH, hyperoxaluria, and hypocalciuria were noted in the dynamic assessment of stone-forming factors ( p  &lt; 0.001). CAT, TAC, and MDA were notably changed in the HFD-fed groups, particularly the HFDD rats. Histological analysis showed that the renal tubules of HFDD rats had the highest scores for both inflammation and renal crystallization deposition ( p  &lt; 0.05). Our results suggest that male SD rats with MS are prone to developing nephrolithiasis. Validation in an  in vivo  model may lead to an understanding of the underlying pathophysiological mechanisms of action of MS-related nephrolithiasis in humans.Key messagesMale SD rats with metabolic syndrome are more prone to developing calcium oxalate nephrolithiasis after treatment with ethylene glycol and ammonium chloride compared to control lean rats.MS-related nephrolithiasis in rats induced by ethylene glycol and ammonium chloride is mainly related to increased hyperoxaluria and inflammation and decreased antioxidant levels.High-fat diet-fed SD rats treated with ethylene glycol and ammonium chloride are a stable and valid  in vivo  model for understanding the potential mechanism of action of MS-related nephrolithiasis. Male SD rats with metabolic syndrome are more prone to developing calcium oxalate nephrolithiasis after treatment with ethylene glycol and ammonium chloride compared to control lean rats. MS-related nephrolithiasis in rats induced by ethylene glycol and ammonium chloride is mainly related to increased hyperoxaluria and inflammation and decreased antioxidant levels. High-fat diet-fed SD rats treated with ethylene glycol and ammonium chloride are a stable and valid  in vivo  model for understanding the potential mechanism of action of MS-related nephrolithiasis.

A pilot dynamic analysis of formative factors of nephrolithiasis related to metabolic syndrome: evidence in a rat model