RAAS Inhibition vs Calcium Channe Blockade in Pediatric CKD

Key Takeaways

• First-line RAAS inhibition was associated with fewer kidney replacement therapy events over 2 years than calcium channel blockade.
• RAAS inhibition was also associated with a lower secondary kidney composite risk and less time with systolic pressure above the 90th percentile, at 29% versus 39%.
• The analysis emulated a target trial using PRESERVE electronic health record data from 13 institutions in 5 PCORnet Clinical Research Networks.

In children and adolescents with CKD starting first-line antihypertensive therapy, RAAS inhibition was associated with a lower adjusted 2-year risk of kidney replacement therapy than calcium channel blockade. The finding appeared in a JAMA Pediatrics original investigation. The primary analysis showed an adjusted hazard ratio of 0.58 (95% CI, 0.40-0.84; P = .004). The comparison reflected routine-care prescribing rather than randomized assignment.

The comparative-effectiveness analysis used target trial emulation and electronic health record data from the PRESERVE study to mirror a pragmatic first-line treatment comparison. The data spanned January 2009 through December 2020 across 13 institutions in 5 PCORnet Clinical Research Networks, with propensity score weighting used to balance baseline factors. Eligible participants were 2 to 20.9 years old with CKD stage 2 to 4 and either systolic pressure above the 90th percentile or diagnosed hypertension. Participants initiated RAAS inhibition or calcium channel blockade, while exclusions included kidney replacement therapy, renal artery stenosis, malignancy, and pregnancy. The cohort included 2762 participants, with 1757 starting RAAS inhibition and 1005 starting calcium channel blockade; median ages were 13.1 and 12.6 years, and about half were male.

The primary endpoint was progression to kidney replacement therapy within 2 years, identified through linkage with the United States Renal Data System. The secondary endpoint combined kidney replacement therapy, a 50% decline in estimated glomerular filtration rate, or eGFR below 15 mL/min/1.73 m2. In intention-to-treat analyses using Cox proportional hazards regression with propensity score stratification, RAAS inhibition was associated with a lower risk of this composite than calcium channel blockade, with an adjusted hazard ratio of 0.67 (95% CI, 0.53-0.83) over the same 2-year follow-up window.

Systolic blood pressure control also differed between groups, with RAAS inhibition associated with less time above the 90th percentile than calcium channel blockade. Adjusted analyses showed the same directional pattern over 2 years. The authors concluded that the findings support first-line RAAS inhibition for antihypertensive treatment in pediatric CKD. The study was an observational target trial emulation based on routine care data rather than a randomized comparison. The associations were observed within the cohort over 2 years.