Dyslipidemia and Kidney Stone Risk: Mechanisms, Clinical Evidence, and Therapeutic Considerations

The prevalence of kidney stone (KS) disease and cardiometabolic diseases are simultaneously increasing in the United States. Dyslipidemia has been associated with an increased risk for KS formation and recurrence due to alterations in metabolism of purine and oxalate along with a defective urinary acidification mediated through insulin resistance. In addition, direct renal lipotoxicity, oxidative stress and crystal-induced inflammation also play a role. Although there are systematic reviews, metabolic analyses, cohort studies, and National Health and Nutrition Examination Survey (NHANES)-based studies on association of specific lipid phenotypes with urinary KS profiles, there is still insufficient evidence to include lipid profiles in metabolic evaluation for recurrent stone disease. Observational data suggest that lipid-lowering therapies may reduce stone risk. In this review, we provide a comprehensive overview of the epidemiological evidence linking dyslipidemia to KS disease, the underlying pathophysiology connecting dyslipidemia and stone formation along with the clinical implications for the metabolic evaluation, and the emerging data on pharmacologic therapies that may offer stone-protective benefits.