Response to the Renin Rise With Aliskiren: It’s Simply Stoichiometry
The data presented by Danser et al1 for the percentage of inhibition of plasma renin by increasing aliskiren doses are important. I would, however, advocate caution in the estimation of renin inhibition in vivo based on theoretical calculations or measurement of plasma renin activity. Although the antibody-capture method of plasma renin assay provides a useful measure of renin inhibition, it may overestimate renin inhibition in vivo, as indicated by plasma angiotensin levels.3,4 Nussberger et al5 showed that, when aliskiren was administered to healthy volunteers at 160 mg/d or 640 mg/d for 8 days, plasma angiotensin II levels were 75% and 55% of control, respectively, when measured 24 hours after the last dose. As I stated in the conclusion to my article, the most reliable measure of renin inhibition in vivo is the change in plasma levels of angiotensin I and II.2
D.J.C. has had research contracts with Solvay Pharmaceutical Company and Novartis in the last 5 years and has been a member of an advisory board for Novartis.
Danser AH, Charney A, Feldman DL, Nussberger J, Fisher N, Hollenberg N. The renin rise with aliskiren: it’s simply stoichiometry. Hypertension. 2008; 51: e27–e28.
Campbell DJ. Interpretation of plasma renin concentration in patients receiving aliskiren therapy. Hypertension. 2008; 51: 15–18.
Nussberger J, Delabays A, de Gasparo M, Cumin F, Waeber B, Brunner HR, Ménard J. Hemodynamic and biochemical consequences of renin inhibition by infusion of CGP 38560A in normal volunteers. Hypertension. 1989; 13: 948–953.
Azizi M, Menard J, Bissery A, Guyene TT, Bura-Riviere A. Hormonal and hemodynamic effects of aliskiren and valsartan and their combination in sodium-replete normotensive individuals. Clin J Am Soc Nephrol. 2007; 2: 947–955.