It Is the Plasma Renin Activity Level That Counts, not Stoichiometry

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HomeHypertensionVol. 52, No. 2It Is the Plasma Renin Activity Level That Counts, not Stoichiometry Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBIt Is the Plasma Renin Activity Level That Counts, not Stoichiometry Jean E. Sealey John H. Laragh Jean E. SealeyJean E. Sealey Department of Medicine, Weil Cornell Medical College, New York, NY Search for more papers by this author John H. LaraghJohn H. Laragh Department of Cardiothoracic Surgery, Weil Cornell Medical College and New York, Presbyterian Hospital, New York, NY Search for more papers by this author Originally published7 Jul 2008https://doi.org/10.1161/HYPERTENSIONAHA.108.116319Hypertension. 2008;52:e20Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 7, 2008: Previous Version 1 To the Editor:We disagree with Danser et al1 that, in patients taking the renin inhibitor aliskiren, “it is the stoichiometry that counts, not the rise in renin.” In fact, plasma renin activity (PRA) is a more explicit indicator than stoichiometry. A PRA fall during aliskiren means that renal renin secretion did not increase by much. A PRA rise means that the increase in renal renin secretion was large enough to overwhelm the aliskiren blockade of PRA. It is that simple.PRA falls during aliskiren therapy in most patients with mild-to-moderate hypertension2 (Figure). However, the magnitude of the fall differs among patients, and PRA actually increases in ≈1 in 20 patients, indicating that aliskiren can be overwhelmed by a reactive rise in renin.3 Moreover, 2 patients reported by Stanton et al2 had >20 mm Hg sustained increases in daytime systolic pressure (measured by ambulatory blood pressure monitoring), thereby indicating that blood pressure can rise during aliskiren. Download figureDownload PowerPointFigure. Medium/high renin patients had PRA >0.3 ng/mL per hour. (The Nussberger assay generates angiotensin I more slowly than the Sealey assay.) Patients with mild-to-moderate hypertension were treated for 4 weeks with 150 mg (triangles) or 300 mg (circles) of aliskiren. Vertical line=1 SD from the median value.Redrawn from Stanton et al.2A rise in blood pressure during aliskiren can alert the clinician to excessive kidney renin secretion; such a patient is likely to respond to a β-blocker, because β-blockers reduce renin secretion. However, there are 2 quite different reasons for the absence of a blood pressure fall during aliskiren. The patient may have had low renin to begin with and no renin to block, or, alternatively, renin secretion may have increased so much that it overcame the blocking action of the drug. PRA will be low in the former type of patient but not in the latter. The low-renin patient is likely to respond to a natriuretic drug,4 whereas adding a natriuretic drug instead of an antirenin drug to the hyperreactive renin patient will increase renin secretion even more to reduce the likelihood of a fall in blood pressure. Thus, knowing the PRA level is what counts, not stoichiometry.Sources of FundingThis work was supported by the May and Samuel Rudin Family Foundation, the Trust of Frederick Schwartz, and the Lawrence M. Gelb Foundation.DisclosuresJ.E.S. and J.H.L. are consultants to Diasorin Inc. J.H.L. has licensed patent 09/657.027, “Method for Evaluating and Treating Hypertension,” to Diasorin Inc.1 Danser AHJ, Charney A, Feldman DL, Nussberger J, Fisher N, Hollenberg N. The renin rise with aliskiren: it’s simple stoichiometry. Hypertension. 2008; 51: e27–e28.LinkGoogle Scholar2 Stanton A, Jensen C, Nussberger J, O'Brien E. Blood pressure lowering in essential hypertension with an oral renin inhibitor, aliskiren. Hypertension. 2003; 42: 1137–11433.LinkGoogle Scholar3 Sealey JE, Laragh JH. Aliskiren, the first renin inhibitor for treating hypertension: reactive renin secretion may limit its usefulness. Am J Hypertens. 2007; 20: 587–597.CrossrefMedlineGoogle Scholar4 Laragh JH. Laragh’s lessons in pathophysiology and clinical pearls for treating hypertension. Lesson XVI. How to choose the correct drug treatment for each hypertensive patient using a plasma renin based method and volume vasoconstriction analysis. Am J Hypertens. 2001; 14: 491–503.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByStanton A, Gradman A, Schmieder R, Nussberger J, Sarangapani R and Prescott M (2009) Aliskiren Monotherapy Does Not Cause Paradoxical Blood Pressure Rises, Hypertension, 55:1, (54-60), Online publication date: 1-Jan-2010. Chaudhary K, Nistala R and Whaley-Connell A (2010) Is there a future for direct renin inhibitors?, Expert Opinion on Investigational Drugs, 10.1517/13543781003781906, 19:5, (653-661), Online publication date: 1-May-2010. Nussberger J, Stanton A, Fisher N, Hollenberg N and Jan Danser A (2008) Response to It Is the Plasma Renin Activity Level That Counts, not Stoichiometry, Hypertension, 52:2, (e21-e21), Online publication date: 1-Aug-2008. August 2008Vol 52, Issue 2 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.108.116319PMID: 18606895 Originally publishedJuly 7, 2008 PDF download Advertisement SubjectsClinical StudiesDiagnostic TestingPharmacology