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

Abstract

Abstract 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. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information.