A 54-year-old man comes to the office for evaluation of hypertension. He was diagnosed with hypertension 2 years ago but has had inconsistent follow-up and has not seen a physician in the last 6 months. The patient is not currently taking any medications but feels well and has good exercise tolerance. He has a family history of hypertension and ischemic stroke. His BMI is 26 kg/m2. Physical examination is unremarkable. Serum creatinine level is normal. The patient is started on valsartan and hydrochlorothiazide, and the following values were measured at baseline (before starting treatment) and after 3 weeks of therapy:
| Blood pressure | Plasma renin activity, morning | |
| Baseline | 165/95 mm Hg | 2.5 ng/mL per hour (normal: 1-4 ng/mL per hour) |
| After 3 weeks | 162/96 mm Hg | 2.4 ng/mL per hour |
Which of the following best explains the observed findings in this patient?
Show Explanatory Sources
Renin converts angiotensinogen to angiotensin I, which is then converted in the lung to angiotensin II, a potent vasoconstrictor that stimulates aldosterone secretion. Plasma renin activity (PRA) is measured as the amount of angiotensin I generated per unit of time and is a useful tool for assessing the function of the renin-angiotensin-aldosterone (RAAS) axis.
ACE inhibitors and angiotensin II receptor antagonists (eg, valsartan) block the RAAS pathway, causing a feedback increase in serum renin levels. Diuretic-induced hypovolemia leads to decreased renal blood flow, which also increases renin levels and activates RAAS. By contrast, drugs that block sympathetic stimulation (eg, beta blockers and clonidine) reduce renin levels. Because this patient's PRA did not increase after being prescribed valsartan and hydrochlorothiazide, this suggests likely medication noncompliance.
(Choice A) Sodium intake increases intravascular volume, which suppresses renin production by inducing pressure natriuresis and increased distal tubule sodium delivery. In contrast, a low sodium diet usually leads to increased serum renin and aldosterone levels. However, this patient's normal PRA makes a low sodium diet less likely.
(Choice C) Obstructive sleep apnea (OSA) is a secondary cause of hypertension but usually does not directly affect PRA. In addition, this patient does not have the typical findings of OSA (eg, excessive daytime sleepiness, snoring at night, obesity).
(Choice D) Primary hyperaldosteronism causes inappropriately elevated serum aldosterone, which suppresses renin production and would cause low serum renin levels.
(Choice E) Renal artery stenosis decreases the effective arterial volume to the kidney, which can lead to increased PRA, increased aldosterone, and elevated blood pressure. This patient has a normal PRA. In addition, initiation of angiotensin II receptor antagonists often cause a precipitous drop in blood pressure, along with acute kidney injury, in patients with underlying renal artery stenosis.
Educational objective:
Plasma renin activity (PRA) is a measure of the amount of angiotensin I generated per unit of time. It provides a useful assessment of the renin-angiotensin-aldosterone axis. Factors that increase PRA include low sodium intake and antihypertensive medications such as diuretics (eg, hydrochlorothiazide), ACE inhibitors, and angiotensin II receptor blockers (eg, valsartan).