Plasma renin activity in young children with heart failure: influence of age, disease and ace inhibitor treatment

Introduction Increased plasma renin activity (PRA) levels may have various causes: PRA has gained importance as prognostic marker for patients with heart failure; age may have an influence on endogenous PRA levels; and ACE inhibitor (ACEi) treatment can also interfere with PRA levels. We aimed to investigate PRA levels in very young children with heart failure, with and without ACEi treatment. Methods As part of a PK-PD study of enalapril for pediatric heart failure (LENA studies), blood samples were collected and analyzed for PRA levels before, 4 hours after and within the first week of enalapril treatment. In addition, a literature search was conducted according to the PRISMA concept in MEDLINE to identify studies on PRA levels in healthy children as well as in children with heart failure in the age range from 1 day up to 2 years. Comparison was performed with LENA study data and with data from 9 healthy volunteers. Results Infants from LENA studies with heart failure (n= 35, aged 25 days – 2.1 years) had median PRA levels of 19.7 (n=35) before, 29.0 (n=34, p>0.05) 4 hours after enalapril dose, and 89.1 ng/mL/h (n=29, p<0.01) after 5 days of treatment. Literature search revealed mean PRA levels in healthy children between 2.3 to 29.8 (n= 14 studies) and 10.0 to 87.1 ng/mL/h in ACEi naïve heart failure children (n= 4 studies). PRA levels of 9 healthy adults ranged between 0.13 to 1.85 ng/mL/h. Conclusions Very young children had higher endogenous PRA levels compared to adults. Heart failure at this age was associated with even higher PRA levels and ACEi treatment further increased PRA levels. These results indicate that patients appear to respond to ACEi treatment but question the value of PRA levels as prognostic marker in this population.