Comparative Effectiveness of Antihypertensive Medications in Children With Chronic Kidney Disease

Abstract

Importance: Hypertension is a major modifiable factor for kidney function decline in chronic kidney disease (CKD). Comparative trials of antihypertensive medications in pediatric CKD are lacking. Objective: To evaluate the comparative effectiveness of renin-angiotensin-aldosterone system inhibition (RAASi) vs calcium channel blockade (CCB), the most widely used first-line antihypertensive treatment approaches in pediatric CKD, on preservation of kidney function. Design, setting, and participants: Using target trial emulation methods, this comparative-effectiveness study emulated a pragmatic, open-label clinical trial using electronic health record data from the Preserving Kidney Function in Children with CKD (PRESERVE) study from January 2009 through December 2020. Thirteen health care institutions from 5 PCORnet Clinical Research Networks were represented. Children and adolescents aged 2 to 20.9 years with CKD stage 2-4 and systolic blood pressure higher than the 90th percentile or with a hypertension diagnosis who initiated treatment with RAASi or CCB were included. Exclusion criteria included kidney replacement therapy, renal artery stenosis, malignancy, and pregnancy. Data analysis was completed in July 2025. Exposures: Incident RAASi or CCB treatment. Randomization was emulated by propensity score weighting to balance groups on sociodemographic factors, institution, year, CKD etiology, proteinuria, CKD stage, obesity, health care use, medications, comorbidities, and blood pressure control (percentage of time at greater than the 90th percentile). Main outcomes and measures: The primary outcome was progression to kidney replacement therapy within 2 years of follow-up, ascertained through linkage with the United States Renal Data System. The secondary outcome was a composite of kidney replacement therapy, 50% decline in estimated glomerular filtration rate, or estimated glomerular filtration rate less than 15 mL/min/1.73 m2. Cox proportional hazards regression with propensity score stratification was used to estimate adjusted hazard ratios (aHRs) in the intention-to-treat analysis. Adjusted analyses also compared systolic blood pressure control within 2 years of follow-up. Results: Of 2762 children and adolescents, 1757 initiated RAASi (median [IQR] age, 13.1 [9.2-15.5] years; 897 [51.1%] male) and 1005 initiated CCB (median [IQR] age, 12.6 [8.4-15.3] years; 500 [49.8%] male). In adjusted analyses, RAASi was associated with reduced risk of both kidney replacement therapy (aHR, 0.58; 95% CI, 0.40-0.84, P = .004) and the secondary composite outcome (aHR, 0.67; 95% CI, 0.53-0.83). Systolic blood pressure control was better with RAASi than CCB (29% vs 39% of time >90th percentile). Conclusions and relevance: In this comparative-effectiveness study, RAASi was associated with lower risk of CKD progression and better blood pressure control compared to CCB. Findings support first-line use of RAASi for antihypertensive treatment in pediatric CKD.