Changes in metabolic overweight phenotypes over time and risk of nephrolithiasis: a cohort study

Overweight/obesity is considered an independent risk factor for nephrolithiasis, but little is known about its effect on nephrolithiasis according to metabolic health status.

We aimed to investigate the association between various metabolic overweight phenotypes and the occurrence of nephrolithiasis. It also explores whether changes in these phenotypes over time influence the risk of nephrolithiasis.

A total of 10,315 participants free of nephrolithiasis who underwent an annual health checkup from 2017 to 2022 were included in our prospective cohort study. They were categorized into four groups according to the presence of overweight and metabolic abnormalities (MA). The primary endpoint was the occurrence of renal stones. Multivariable Cox analysis was conducted to elucidate the relationship between metabolic overweight phenotypes and incident nephrolithiasis.

During a median follow-up duration of 4.02 years, nephrolithiasis occurred in 1,468 (14.23%) participants. In the full cohort, we observed that the 5-year cumulative incidences of nephrolithiasis were highest in the metabolically healthy overweight (MHO) and metabolically abnormal overweight (MAO) groups. The hazard ratios (HRs) for nephrolithiasis, relative to metabolically healthy normal weight (MHNW), ranged from 1.19 (95% CI:1.03-1.37; MHO) to 1.32 (95% CI:1.15-1.51; MAO). Furthermore, individuals with persistent MHO throughout follow-up were at a 1.42-fold increased risk of nephrolithiasis (P < 0.001), and 32.17% of individuals experienced changes in phenotype during follow-up. Among MAO subjects, those who transitioned to MHO and MHNW had a 26% and 45% lower risk of incident nephrolithiasis, respectively, compared to those who persisted in the MAO phenotype.

Individuals in the MHO and MAO groups exhibit an elevated risk of incident nephrolithiasis in this prospective cohort study. A significant proportion of nephrolithiasis cases may be potentially preventable through the appropriate management of metabolic risk factors for MAO subjects.