A comparison of the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses

Abstract

Purpose: To compare the clinical characteristics of pediatric urolithiasis patients with positive and negative molecular diagnoses.

Methods: The clinical characteristics corresponding to pediatric urolithiasis patients that had undergone exome sequencing at our hospital between January 2016 and May 2021 were collected. Genetic analysis results were used to separate patients into positive and negative molecular diagnosis groups. Multivariate logistic regression analyses adjusted for visiting age, sex, ethnicity, province, and body mass index were used to compare differences in medical history, diagnostic imaging findings, and renal function between individuals with and without molecular diagnoses.

Results: In total, 194 patients with pediatric urolithiasis of unknown etiology underwent exome sequencing and were included in the present study, of whom 63 obtained urolithiasis-related molecular diagnoses. Relative to cases without a molecular diagnosis, those with a positive molecular diagnosis were more likely to be associated with a positive family history (OR 2.84, 95% CI 1.29-6.29, p = 0.008), consanguineous parents (OR 24.7, 95% CI 1.34-454, p = 0.002), early onset (OR 1.26, 95% CI 1.09-1.45, p < 0.001), nephrocalcinosis (OR 10.6, 95% CI 3.06-36.6, p < 0.001), cast stone (OR 18.9, 95% CI 4.40-81.1, p < 0.001), multiple stones (OR 13.9, 95% CI 6.39-30.2, p < 0.001), bilateral stones (OR 7.04, 95% CI 3.47-14.2, p < 0.001), a lower estimated glomerular filtration rate (OR 1.17, 95% CI 1.07-1.28, p < 0.001), and chronic kidney disease (OR 26.9, 95% CI 1.42-526, p < 0.001).

Conclusion: A positive family history, consanguineous parents, early onset, nephrocalcinosis, severe stone burden, and impaired renal function are signals of concern that are suggestive of inherited urolithiasis.

Keywords: Exome sequencing; Inherited disease; Pediatric urolithiasis; Phenotypic analysis.