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RAAS inhibitors show pediatric CKD benefit vs. calcium channel blockers

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April 30, 2026

2 min read

Key takeaways:

  • Renin-angiotensin-aldosterone system (RAAS) inhibitors conferred reduced risks for starting dialysis or needing a kidney transplant.
  • Risks for any adverse event were lower in the RAAS inhibitor treatment group.

Renin-angiotensin-aldosterone system inhibitors were linked to better pediatric chronic kidney disease outcomes compared with calcium channel blockers, according to study data published in JAMA Pediatrics.

Renin-angiotensin-aldosterone system (RAAS) inhibitors and calcium channel blockers (CCBs) are two primary antihypertensive treatments used in the pediatric population, according to Michelle R. Denburg, MD, MSCE, associate professor of pediatrics (nephrology) at the Children’s Hospital of Philadelphia, and colleagues. However, few trials have compared the effectiveness of both antihypertensive medications in a cohort of pediatric patients with CKD, they wrote.



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Data derived from Denburg MR, et al. JAMA Pediatr. 2026;doi:10.1001/jamapediatrics.2026.0207.

“We used target trial emulation methods to evaluate the real-world comparative effectiveness of the most widely used first-line antihypertensive treatments in pediatric CKD,” Denburg and colleagues wrote.

In a comparative effectiveness study, the researchers reviewed electronic health record data from 1,757 children and adolescents prescribed RAAS inhibitors (median age, 13.1 years; 51.1% boys; 46.9% white) and 1,005 prescribed CCBs (median age, 12.6 years; 50.2% girls; 45.5% white) from the PRESERVE study from 2009 to 2020. Patients were included if they had CKD stage 2 to 4 and a systolic blood pressure higher than the 90th percentile or a hypertension diagnosis.

The primary outcome evaluated whether patients began a kidney replacement therapy treatment (dialysis or kidney transplant) within 2 years. The secondary outcome was a composite of starting a kidney replacement therapy, eGFR decline of at least 50% or kidney failure.

Results showed patients treated with RAAS inhibitors had reduced risks for initiating kidney replacement therapy (adjusted HR = 0.58; 95% CI, 0.4-0.84) and the composite outcome (aHR = 0.67; 95% CI, 0.53-0.83) compared with CCBs.

Additionally, patients treated with RAAS inhibitors had better systolic BP control compared with CCBs, defined by the amount of time spent above the 90th percentile for systolic BP (29% vs. 39%).

Compared with CCBs, RAAS inhibitors were associated with lower risks for any adverse event (HR = 0.82; 95% CI, 0.74-0.9), edema (HR = 0.76; 95% CI, 0.59-0.98), anemia (HR = 0.74; 95% CI, 0.62-0.89), leukocytopenia (HR = 0.76; 95% CI, 0.62-0.93), stomatitis (HR = 0.41; 95% CI, 0.26-0.67) and elevated liver enzymes (HR = 0.71; 95% CI, 0.54-0.92). Conversely, the RAAS inhibitor group had greater risks for hypotension (HR = 1.55; 95% CI, 1.03-2.35) and hair loss (HR = 1.94; 95% CI, 1.02-3.69).

Exploratory subgroup analysis showed patients with nonglomerular disease had significantly lower risks for beginning kidney replacement therapy (aHR = 0.53; 95% CI, 0.32-0.88) and the composite outcome (aHR = 0.62; 95% CI, 0.41-0.81). Changes among patients with glomerular disease did not reach statistical significance, according to the researchers.

Overall, RAAS inhibitor use was associated with better kidney preservation and BP control vs. CCBs, according to the researchers.

“These findings support first-line use of RAAS inhibitors for antihypertensive therapy in children with CKD,” Denburg and colleagues wrote.

Perspective

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Darcy K. Weidemann, MD, MHS, FAAP

This is a timely and clinically relevant comparative effectiveness study evaluating two of the most commonly prescribed antihypertensive classes in pediatric CKD: angiotensin-converting enzyme (ACE) inhibitors and CCBs. This work should be of particular interest to the pediatric nephrology community, as it addresses a persistent gap between evidence generated under controlled trial conditions and the realities of day-to-day clinical practice.Rather than focusing on efficacy under idealized conditions, the authors directly compare two active, clinically relevant treatment options — precisely the decision clinicians face when selecting initial antihypertensive therapy for children with CKD. By moving beyond placebo-based paradigms, the findings are immediately applicable to clinical decision-making and discussions with patients and families.This approach is especially well suited to the complexities inherent in antihypertensive selection in pediatric CKD. Although RAAS blockade with ACE inhibitors has traditionally been favored because of potential renoprotective benefits, this preference carries meaningful trade-offs. Initiation of RAAS blockade often necessitates increased laboratory monitoring, including surveillance for rises in serum creatinine and hyperkalemia, and can prompt difficult judgments regarding the clinical significance of creatinine changes. In adolescents capable of pregnancy, counseling around potential teratogenicity adds another layer of complexity. In real-world practice, these considerations translate into increased visits, additional testing, caregiver anxiety and clinician workload.By contrast, CCBs are generally simpler to initiate and maintain, with fewer monitoring requirements and a more straightforward adverse effect profile. Despite their widespread use, direct comparative data between these two approaches in pediatric CKD has been limited. The study by Denberg and colleagues helps fill this gap, demonstrating improved effectiveness of RAAS blockade for blood pressure control and kidney disease outcomes while showing a similar overall safety and adverse event profile compared with CCBs — an important reassurance when weighing treatment burden against benefit.A particularly notable finding is the consistency of observed benefits across both glomerular and nonglomerular CKD subgroups. Given that the majority of pediatric CKD is nonglomerular and often nonproteinuric — frequently affecting younger children for whom laboratory monitoring may pose additional logistical and emotional barriers — these results are especially impactful. Having real-world data demonstrating improved blood pressure control and mitigation of long-term kidney disease progression strengthens the clinician’s ability to counsel families on the value of RAAS blockade, even when the short-term burdens are substantial.By leveraging data from the PRESERVE study integrated electronic health record cohort encompassing 15 health systems, this study provides pragmatic insight into treatment effectiveness across diverse practice settings. In sum, this study offers not only important guidance regarding antihypertensive choice in pediatric CKD, but also a compelling example of how real-world evidence can inform nuanced clinical decisions in areas of true equipoise.

Darcy K. Weidemann, MD, MHS, FAAP

  • Healio | Nephrology News & Issues Editorial Advisory Board Member
  • Pediatric nephrologist
  • Children’s Mercy
  • Kansas City, Missouri


Disclosures: Weidemann reports no relevant financial disclosures.

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