Metabolically healthy and unhealthy obesity phenotypes and risk of renal stone: a cohort study

Background/Objectives: Although obesity is considered an independent risk factor of nephrolithiasis, little is known about the effect of obesity on nephrolithiasis according to metabolic health status. We investigated the association between body mass index (BMI) category and the incidence of nephrolithiasis in metabolically healthy and unhealthy individuals. Subjects/Methods: The cohort consisted of 270,190 Korean adults free of nephrolithiasis at baseline, who were followed-up annually or biennially for a median of 4.1 years. Nephrolithiasis were determined based on ultrasonographic findings. Being metabolically healthy was defined as not having any metabolic syndrome component. A parametric Cox model was used to estimate the adjusted hazard ratios (HRs) with 95% confidence intervals (CIs). Results: During 1,415,523.0 person-years of follow-up, 13,450 participants developed nephrolithiasis (incidence rate, 9.5 per 1000 person-years). Obesity was positively associated with an increased risk of incident nephrolithiasis in dose-response manner, but the association was stronger in metabolically healthy individuals. Among metabolically healthy individuals, the multivariable-adjusted HRs (95% CIs) for incident nephrolithiasis comparing BMIs 23–24.9, 25–29.9, and ≥30 with a BMI of 18.5–22.9 kg/m ² as the reference were 1.02 (0.95–1.10), 1.12 (1.03–1.22), and 1.72 (1.21–2.44), respectively, whereas corresponding HRs (95% CIs) in metabolically unhealthy individuals were 1.10 (1.04–1.17), 1.27 (1.20–1.34), and 1.36 (1.22–1.51), respectively. The association between obesity and incident nephrolithiasis was stronger in men and current smokers. Conclusions: Obesity was associated with a higher incidence of nephrolithiasis in both metabolically healthy and unhealthy individuals, indicating obesity per se as an independent risk factor for nephrolithiasis.