“Effective” Plasma Renin Activity: A Derived Measure for Assessing Residual Plasma Renin Activity in Patients Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers
To the Editor:
The plasma renin activity (PRA) test quantifies the circulating activity of the renin-angiotensin system by measuring the rate at which renin forms angiotensin I (Ang I) in plasma. The PRA test overestimates the true activity of the circulating renin-angiotensin system in patients taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) because these drugs block the system at sites distal to the enzymatic release of Ang I by plasma renin.1,2
When patients are taking these drugs, a simple calculation can be used to determine their residual “effective” PRA (ePRA). At clinical doses, ACEIs allow ≈10% of Ang I to be converted to Ang II, whereas ARBs allow ≈10% of Ang II to bind to Ang II type 1 receptors.3 Therefore, the ePRA is ≈10% of the PRA value in patients taking one of these agents and ≈1% in patients taking both agents. In contrast, PRA, per se, truly reflects the circulating renin-angiotensin system activity in patients taking other antihypertensive drug types. For example, if a patient with a PRA of 2 ng/mL/h is taking a diuretic, calcium channel blocker, β-blocker, or a direct renin inhibitor, the ePRA is truly 2 ng/mL/h, that is, in the medium range. However, if that same patient is also taking an ACEI or ARB, the effective PRA is ≈0.2 ng/mL/h, demonstrating that the renin-angiotensin system has been adequately blocked. Thus, the ePRA is ≈10% of the reported PRA, because ≈90% of its functional activity has been blocked by the ACEI or ARB.
Applying this reasoning to the report of Pimenta et al,4 in which dietary sodium deprivation lowered blood pressure in resistant hypertensives who were taking an ACEI or an ARB, a significant blood pressure fall with sodium restriction could have been anticipated. The ePRA was suppressed at baseline (0.11 ng/mL/h) and during both the 250- and 50-mmol salt diets (<0.06 and 0.27 ng/mL/h, respectively), thereby allowing the blood pressure to fall when dietary sodium deprivation led to a fall in body sodium.
In summary, by using PRA testing and by calculating ePRA, it becomes possible to determine whether renin system activity has been adequately blocked by ACEIs and/or ARBs. This approach can simplify the drug selection process and lead to appropriate dietary sodium recommendations for uncontrolled hypertensive patients treated with ACEIs or ARBs.
Sources of Funding
This work was supported by the May and Samuel Rudin Family Foundation, Lawrence M. Gelb Foundation, Trust of Frederick Schwartz, Starr Foundation, and Wallace Foundation.
J.E.S. is a consultant for Diasorin Inc (Stillwater, MN). J.H.L. is a consultant for Diasorin Inc and licensed patent No. 09/657 027, “Method for Evaluating and Treating Hypertension,” to Diasorin Inc.
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