BackgroundCaregivers of children with nephrotic syndrome may experience psychological challenges due to the disease’s unpredictability and home monitoring burden. Prevalence and risk factors of distress, anxiety, and depression among these caregivers are unknown.MethodsWe analyzed data from Insight into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics, a prospective observational childhood nephrotic syndrome cohort. We included children (1–18 years) diagnosed from 1996–2023 from the greater Toronto area, Canada, and their caregivers. Children had annual study visits for five years. Caregivers were screened for anxiety and depression using the Patient Health Questionnaire-4 annually. We evaluated risk factors for psychological distress using mixed effects models.ResultsWe analyzed data from 733 children with nephrotic syndrome (median age at diagnosis: 4 [IQR 3–6] years; 460 [73%] male; 242 [33%] South Asian; 690 [94%] steroid-sensitive). Median follow-up was 5.4 (IQR 3.0–9.3) years. Caregivers of 261 (36%) children experienced ≥ mild, 101 (14%) experienced ≥ moderate, and 38 (5%) experienced severe psychological distress. Caregivers of 167 (23%) children screened positive for anxiety and 90 (12%) for depression during follow-up. Risk factors for psychological distress were younger child age, parental unemployment, worse child quality-of-life, worse family functioning, language barrier, active steroid treatment, and lack of steroid-sparing treatment. Distress was associated with a higher probability of subsequent steroid-sparing medication initiation (adjusted odds ratio 1.08, 95%CI 1.02–1.15), although residual confounding and reverse causation cannot be excluded.ConclusionsOver one-third of caregivers experienced mild or greater psychological distress, 23% screened positive for anxiety, and 12% for depression. Child and caregiver demographics, treatment response, and socioeconomic elements were predictive of caregiver distress.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information