Incidence and Risk Factors for Hypertension among Children with Nephrotic Syndrome

To determine incidence and risk factors for hypertension in childhood nephrotic syndrome. Using data from the Insight into Nephrotic Syndrome (INSIGHT) study, a prospective observational childhood nephrotic syndrome cohort from Toronto, Canada, we evaluated hypertension incidence and time-to-hypertension overall and stratified by 1) steroid-resistance or steroid-sensitivity, and 2) frequently-relapsing, steroid dependent, or infrequently-relapsing. Hypertension was defined as stage 1-2 hypertensive blood pressure on two consecutive visits or anti-hypertensive medication initiation. We included 748 children with nephrotic syndrome from 1996 to 2023. Median (quartile 1-3 [Q1-3]) age at diagnosis was 4 (2.8-6) years, 473 (63%) children were male, and 240 (32%) were of South Asian ethnicity. Forty (5%) children were steroid-resistant, 177 (24%) steroid-dependent, 113 (15%) frequently-relapsing, and 418 (56%) infrequently-relapsing. Median follow-up was 5.2 years (Q1-3 3.0-9.3). During follow-up, 393 (53%) children developed hypertension or were initiated on an anti-hypertensive medication (incidence rate 8.2 per 100 person-years, 95%CI 7.4-9.1). Hypertension was more common among children steroid-resistance than steroid-sensitivity (70% vs. 52%; adjusted HR 1.47, 95%CI 1.00-2.17). Hypertension was also more common in children who were steroid-dependent (67%; adjusted HR 1.81, 95%CI 1.43-2.30) and frequently-relapsing (63%; adjusted HR 1.64, 95%CI 1.23-2.18), than infrequently-relapsing (42%). Among steroid-sensitive patients, higher BMI Z-score and academic center were also significant hypertension risk factors. Half of children with nephrotic syndrome develop hypertension. Children who are steroid-resistant, steroid-dependent, frequently-relapsing or have obesity are at greatest risk. Close blood pressure surveillance is justified to identify and treat hypertension.