When Stones Begin: Age of Onset Reveals the Systemic Metabolic Nature of Nephrolithiasis

Background: Kidney stone disease is a common urological condition with a rising worldwide incidence. Although multiple metabolic and lifestyle risk factors have been identified, determinants influencing the age at which symptoms begin remain poorly defined. Understanding factors associated with earlier disease presentation may improve prevention strategies. Methods: This observational cohort study included 546 patients with confirmed nephrolithiasis. Participants were stratified into early-onset (< 45 years) and late-onset (≥ 45 years) groups. Sociodemographic, lifestyle, clinical, urinalysis, and biochemical data were collected. Group comparisons were performed using the Chi-square test. Multivariable linear regression analyses evaluated independent associations between age of onset and clinical, laboratory, and hormonal variables. Statistical significance was set at p < 0.05. Results: Early-onset disease accounted for 57.1% of cases. Higher body mass index, smoking, functional status, employment, and education level were significantly associated with age of onset ( p < 0.001). Several comorbidities, including hypertension, diabetes mellitus, cardiovascular disease, renal impairment, gout, gallstones, and renal cell carcinoma, were inversely associated with age of onset. Regression analyses confirmed younger onset as an independent predictor of hypertension (β = − 0.374), diabetes (β = − 0.381), heart disease (β = − 0.253), renal impairment (β = − 0.110), gout (β = − 0.120), and gallstones (β = − 0.148) ( p < 0.05). Urinalysis parameters showed limited associations, with urinary crystals as the only significant predictor ( p = 0.012). Elevated serum urea and calcium were independently associated with earlier onsets. Conclusion: Early-onset nephrolithiasis is strongly associated with metabolic and cardiovascular comorbidities and specific biochemical abnormalities. Age of onset may serve as a clinically meaningful marker for risk stratification and targeted preventive interventions. Keywords: nephrolithiasis, age of onset, cardiometabolic comorbidities, biochemical risk factors, risk stratification