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

Abstract

Introduction and objective 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. Methods 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. Results MS-related parameters, such as BW, LI, BG, TC, and TG, were significantly higher in HFD-fed rats than in RD-fed rats ( p < 0.001). In the HFDD group, significantly lower urinary pH, hyperoxaluria, and hypocalciuria were noted in the dynamic assessment of stone-forming factors ( p < 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 < 0.05). Conclusions 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 messages 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.

Relationship Between Body Mass Index and Blood Lipids with Kidney Stone Disease: The Fasa Adults Cohort Study

“…For instance, a 2019 -2020 study in China found that 14.5% of patients with metabolic syndrome had kidney stones, compared to 7.95% of non-metabolic syndrome patients (10). Experimental studies in rats fed a high-fat diet, simulating obesity-related metabolic syndrome, demonstrated decreased urine pH and elevated levels of hyperoxalemia, hypercalciuria, triglycerides, blood sugar, and total cholesterol, all contributing to kidney stone formation and crystal deposition (13). Additionally, Yoshimura et al identified BMI as an independent factor in the prevalence of kidney stones (14).…”

Clinical Lipid Metabolism Correlates with Urinary Calculus: TyG Index Has a Closer Correlation

“…All these factors are related to the formation of kidney stones. In particular, calcium oxalate stones are related to the concentration of oxalate and calcium ions in urine [22,23] . Therefore, abnormal lipid metabolism may affect the formation of kidney stones by affecting mineral concentration and pH in urine.…”