Safety Concerns of Angiotensin II Receptor Blockers in Preschool Children

Abstract

Two recent trials of angiotensin II receptor blockers (ARBs) were performed in children 0-5 years of age. Data from the published reports of these trials together with additional information from the sponsoring drug companies were obtained. Three deaths occurred in the 183 (1.6%) hypertensive children participating in the two trials. At least two of these deaths occurred in children known to be susceptible to drugs acting on the renin-angiotensin system, that is, children with ongoing nephrotic syndrome and acute gastroenteritis. Clinicians who prescribe ARBs in preschool children need to be aware of the risk of drug toxicity especially in children susceptible to intravascular dehydration. Clinicians should consider discontinuing the drugs in the presence of acute diarrhoea.

IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome

“…Therefore, in children with confirmed or suspected SRNS, this treatment may be commenced as early as 4 weeks from PDN initiation, during the so-called confirmation period. However, ACEi/ARBs may increase the risk for AKI, especially in patients with advanced CKD or intravascular volume depletion [44,45]. Combined treatment with ACEi and ARBs is discouraged due to the increased risk for adverse events including AKI and death [46].…”

KDOQI US Commentary on the 2021 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD

“…Use in very young children (<6 years of age) can be especially problematic given the frequency of childhood illnesses that result in volume depletion, which can lead to AKI and even death from AKI, which has been seen in pediatric trials of these agents. 76 The KDOQI work group agrees with this recommendation to improve BP control and mitigate the progression of CKD in children.…”

Chapter 6: Blood pressure management in children with CKD ND

“…Clinicians should consider discontinuing the drugs in the presence of acute diarrhea. 338 Additionally we recognize that reaching a target of less than the 50 th percentile BP may be quite difficult in some children with CKD. The risks of polypharmacy have to be weighed against the potential benefits of achieving lowered BP.…”

“…Additionally, as mentioned above, discontinuing these agents during episodes of diarrheal illness and dehydration should be considered. 338 …”