Is there an interaction between hypertension and proteinuria in pediatric chronic kidney disease progression? Evidence from the SP-CKD-Kids cohort.

BACKGROUND: Hypertension and proteinuria are established risk factors for chronic kidney disease (CKD) progression in children. Given their pathophysiological interrelationship, whether their coexistence produces a multiplicative interaction remains uncertain. We evaluated this interaction in a Brazilian pediatric cohort. METHODS: This multicenter prospective cohort (SP-CKD-Kids) included 254 children and adolescents aged 1-17 years at study entry with CKD stages 3-4, followed for a median of 3.2 years. The composite outcome comprised death, initiation of kidney replacement therapy, or > 50% decline in estimated glomerular filtration rate (eGFR). Cox models were adjusted for age, sex, baseline eGFR, and CKD etiology. Multiplicative interaction was assessed using a hypertension × proteinuria product term, and statistical power was evaluated by simulation. RESULTS: Hypertension was present in 67.3% of participants and proteinuria in 77.1%; 98 participants (38.6%) experienced the composite outcome. After adjustment, hypertension (hazard ratio [HR] 1.7; 95% confidence interval [CI] 1.0-2.8) and proteinuria (HR 3.5; 95% CI 1.7-7.0) remained independently associated with CKD progression. Participants with both conditions had the highest risk compared with those with neither condition (HR 8.4; 95% CI 2.1-34.2). The multiplicative interaction was not statistically significant (HR 0.6; 95% CI 0.1-3.0; p = 0.507), and simulation indicated limited power to detect interaction effects. CONCLUSIONS: Hypertension and proteinuria were independent predictors of CKD progression in children. Although no statistically significant multiplicative interaction was detected, the wide confidence interval around the interaction term indicates that a clinically relevant interaction cannot be excluded.