Incidence and Risk Factors for Hypertension among Children with Nephrotic Syndrome

Objectives: To determine incidence and risk factors for hypertension in childhood nephrotic syndrome.

Study design: 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.

Results: 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.

Conclusions: 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.