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(Hypertension. 2008;52:e20.)
© 2008 American Heart Association, Inc.

Letters to the Editor

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

Department of Medicine, Weil Cornell Medical College, New York, NY

John H. Laragh

Department of Cardiothoracic Surgery, Weil Cornell Medical College and New York, Presbyterian Hospital, New York, NY

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.

View larger version (10K): [in this window] [in a new window]   Figure. 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.2

A 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.

	Acknowledgments

 
Sources of Funding

This work was supported by the May and Samuel Rudin Family Foundation, the Trust of Frederick Schwartz, and the Lawrence M. Gelb Foundation.

Disclosures

J.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.

	References

Top References

 
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.[Free Full Text]

2. 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.[Abstract/Free Full Text]

3. 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.[CrossRef][Medline] [Order article via Infotrieve]

4. 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.[CrossRef][Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				J. Nussberger, A. Stanton, N. D.L. Fisher, N. K. Hollenberg, and A.H. Jan Danser Response to It Is the Plasma Renin Activity Level That Counts, not Stoichiometry Hypertension, August 1, 2008; 52(2): e21 - e21. [Full Text] [PDF]

This Article Extract Full Text (PDF) All Versions of this Article: 52/2/e20    most recent HYPERTENSIONAHA.108.116319v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sealey, J. E. Articles by Laragh, J. H. Search for Related Content PubMed PubMed Citation Articles by Sealey, J. E. Articles by Laragh, J. H. Related Collections Cardiovascular Pharmacology Clinical Studies Other diagnostic testing