Risk factors for subsequent stone events in pediatric nephrolithiasis: A multi-institutional analysis

Introduction Children with nephrolithiasis have a 50% risk of recurrence 3 years following an index urinary stone event. The American Urological Association guidelines for medical management of nephrolithiasis suggest metabolic evaluations be stratified according to risk of future stone events. However, no such risk stratification exists across the pediatric population with urinary stone disease. We aim to assess the risk factors among pediatric patients for a subsequent stone event (SSE). Materials and methods A retrospective review for children <17 years of age with a diagnosis of nephrolithiasis and at least one completed follow-up at two tertiary-care children's hospitals within our state between 2012 and 2017 was performed. Children with known monogenic stone disease were excluded as well as those with follow-up less than 1 year. SSEs following initial diagnosis and treatment for nephrolithiasis were defined as follows: subsequent surgical intervention, new stone on imaging, reported stone passage, or ED evaluation for renal colic. Clinical and demographic factors were compared between patients with and without SSEs and analyzed using univariate and multivariate analyses via Cox proportional hazard models. Survival curves for significant associations for SSEs were generated and evaluated using LogRank and Wilcoxon comparisons. Results A total of 200 patients with median clinical followup of 2.9 years were analyzed. Median age was 11.5 years (IQR: 6.0-15.5), with 109 (54.5%) males and 91 (45.5%) females, 94 (47%) of whom had a relevant comorbidity. An SSE occurred in 82 patients (41.0%). Age >12 (HR 2.21, 95%CI 1.42-3.45), reported stone event prior to enrollment encounter (i.e. personal history of nephrolithiasis) (HR 1.82, 95%CI 1.14-2.89), and family history of nephrolithiasis (HR 1.62, 95%CI 1.05-2.51) were associated with SSE on univariate analysis while age >12 (HR 2.09, 95%CI 1.33-3.27) and personal history of nephrolithiasis (HR 1.63, 1.02e2.6) retained significance on multivariable analysis. Survival analysis shows increased risk of recurrence with accumulation of risk factors (Summary Figure). Sensitivity analysis accounting for missing family history data retained significance for all three variables. Conclusions Adolescent age and a personal history of nephrolithiasis are independent risk factors for SSE in children. Understanding these risk factors and the nature of SSE among the pediatric population can potentially enhance counseling for further metabolic work-up and tailored clinical follow-up.