In the management of hypertension in paediatric chronic kidney disease (CKD), renin-angiotensin-aldosterone system inhibition (RAASi) is associated with better kidney function preservation and blood pressure (BP) control compared with calcium channel blockade (CCB), according to a real-world comparative-effectiveness study.
In a cohort of children and adolescents with CKD stage 2–4 and elevated systolic BP or with a hypertension diagnosis initiating BP-lowering treatment for the first time, the risk of progression to kidney replacement therapy within 2 years of follow-up was 42-percent lower for those who received RAASi vs CCB (3.2 percent vs 9.1 percent; adjusted hazard ratio [aHR], 0.58, 95 percent confidence interval [CI], 0.40–0.84; p=0.004). [JAMA Pediatr 2026;doi:10.1001/jamapediatrics.2026.0207]
Similarly, the risk of the composite outcome of kidney replacement therapy, 50-percent decline in estimated glomerular filtration rate (eGFR), or eGFR <15 mL/min/1.73 m2 was significantly reduced in the RAASi arm than in the CCB arm (9.2 percent vs 22.8 percent; aHR, 0.67, 95 percent CI, 0.53–0.83).
Paediatric patients who received RAASi also had better BP control, spending 11-percent (95 percent CI, −15 to −8) less time above the 90th percentile for systolic BP compared with those who received CCB (29 percent vs 39 percent).
As for safety, RAASi was associated with a lower risk of edema, cytopenias, and abnormal liver enzymes but a higher risk of hypotension and hair loss relative to CCB.
Beneficial in nonglomerular CKD
In subgroup analyses, the beneficial effect of RAASi was consistently observed in paediatric patients with nonglomerular CKD for both progression to kidney replacement therapy (aHR, 0.53, 95 percent CI, 0.32–0.88) and the composite outcome (aHR, 0.62, 95 percent CI, 0.41–0.81). However, in those with glomerular CKD, the effect was attenuated (aHR, 0.94, 95 percent CI, 0.56-1.57 and aHR, 1.17, 95 percent CI, 0.80–1.73, respectively).
“The replication of findings from the main analysis within the nonglomerular subgroup is a particularly important contribution. The lack of consensus on first-line antihypertensive therapy in paediatric CKD applies predominantly to those with nonglomerular and nonproteinuric CKD, which represents most of paediatric CKD,” the authors said.
Target trial framework
The study was a target trial emulation conducted using multi-institutional real-world electronic health record data from the PRESERVE cohort. The analysis included 2,762 children and adolescents, of whom 1,757 were initiated on RAASi (median age 13.1 years, 51.1 percent male) and 1,005 were initiated on CCB (median age 12.6 years, 49.8 percent male).
In the RAASi arm, lisinopril was the most common medication prescribed (63.4 percent), followed by enalapril (24.3 percent) and losartan (10.1 percent). In the CCB arm, 95.7 percent of the paediatric patients received amlodipine, while 4.3 percent received extended-release nifedipine or isradipine.
“To our knowledge, there have been no comparative trials of antihypertensive medications in paediatric CKD… In the absence of randomized clinical trial data, the target trial framework, unprecedented size of the study sample, unselected study population, and real-world setting of this study provide robust evidence in support of first-line use of RAASi,” according to the authors.
“This is consistent with existing clinical practice guidelines and prior observational data and uniquely addresses an evidence gap for nonglomerular CKD,” they said.