Associations Between Toxic Metal Exposure and Childhood Nephrotic Syndrome

Introduction: Mercury intoxication causes nephrotic syndrome in children and adults. It is unknown if chronic low-grade metal exposure is a risk factor for childhood nephrotic syndrome. We aimed to evaluate the associations between metal exposure and childhood nephrotic syndrome outcomes. Methods: We analyzed data from the Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics (INSIGHT) study, a prospective childhood nephrotic syndrome cohort. We included children (aged 1-18 years) with nephrotic syndrome from the Greater Toronto Area, Canada, excluding congenital or secondary nephrotic syndrome. Toenail clippings were collected and tested for total mercury, copper, arsenic, selenium, cadmium, tin, and lead concentrations. We evaluated associations between individual and mixed metal concentrations and relapse rate, steroid resistance, frequent relapses or steroid dependence, and steroid-sparing immunosuppression use using regression analysis. Results: Nail samples from 298 children with nephrotic syndrome were analyzed. Less than 1% had nail mercury and 10% had other metal concentrations above the reference limits. None had metal concentrations in a potentially toxic range. There were no significant associations between nail mercury concentration and nephrotic syndrome relapses (relative rate: 1.05, 95% confidence interval [CI]: 0.96-1.14), steroid resistance (odds ratio: 0.90, 95% CI: 0.59-1.32), frequent relapses or steroid dependence (odds ratio: 1.01, 95% CI 0.83-1.24), or steroid-sparing medication use (odds ratio: 1.12, 95% CI: 0.92-1.35). In addition, concentrations of other individual or combined metals were not associated with nephrotic syndrome outcomes. Conclusion: Evidence of high exposure to mercury and other toxic heavy metals is rare among Canadian children with nephrotic syndrome. We did not find evidence that chronic exposure to toxic heavy metals is associated with nephrotic syndrome outcomes.