At a Glance

Suspicion of secondary hyperaldosteronism is raised by moderate to severe hypertension that is relatively unresponsive to therapy, combined with evidence of renovascular disorders or diagnoses that may be associated with renovascular disorders. Abdominal bruits serve as a clinical sign of vascular stenosis. Difference in kidney size or unexplained renal insufficiency also raises clinical suspicion. Most patients with hypertension have essential hypertension of unknown cause, but renovascular hypertension is one of the more common forms of secondary hypertension.

In adults younger than 30 years of age, renal artery stenosis may result from fibromuscular dysplasia of renal vessels. In patients older than 50 years of age, atherosclerosis is the leading cause; less frequent causes are renal artery aneurysm, renal vascular thrombosis, and other processes, such as vasculitis affecting renal vessels. Occasionally, external masses may compress the renal artery. Rarely, renin is produced by renal tumors. Hypokalemia in the absence of diuretic therapy is suggestive of hyperaldosteronism. Secondary hyperaldosteronism also occurs as a physiological mechanism in hypotensive states, such as cardiac failure, but the present discussion focuses on presentation with hypertension.

Renin is produced by the juxtaglomerular apparatus in the kidney when it senses a fall in pressure in the renal artery. This is the first step in the renin-angiotensin-aldosterone system (RAAS). Renin production usually occurs when there is a systemic fall in blood pressure. However, this normal regulation fails when there is obstruction to a renal artery. The kidney senses a low pressure, releases increased amount of renin, and activates the RAAS. Increased production of angiotensin causes vasoconstriction, and production of aldosterone results in increased sodium uptake and potassium excretion by the kidney. Sodium retention increases vascular volume and blood pressure.

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What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Testing for plasma renin helps identify secondary hyperaldosteronism. Renin can be determined either by using a direct immunoassay of renin molecules or by measuring renin activity by assessing rate of angiotensin production in a test tube. High plasma renin supports the clinical diagnosis, but this test is considered to have a sensitivity and specificity of only about 60%. Measuring the aldosterone:renin ratio helps distinguish secondary from primary aldosteronism. In both disorders, aldosterone is high, but, in primary aldosteronism, renin should be suppressed, as opposed to high in secondary hyperaldosteronism (Table 1).

Table 1.
Plasma renin Plasma aldosterone Serum potassium
High High Low or normal

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications – OTC drugs or Herbals – that might affect the lab results?

Many factors affect renin measurement and may contribute to low sensitivity and specificity of the plasma renin test. In general, renin production is increased by factors that lower blood pressure and vascular volume, and it is decreased by factors that increase blood pressure and vascular volume. Renin production is suppressed by high sodium intake, intravenous fluid loading, supine posture, beta blockers, and nonsteroidal anti-inflammatory drugs. Renin production is increased by sodium restriction, volume depletion, diuretics, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers. Renin activity assays are inhibited by renin inhibitors. Renal glomerular injury may impair the ability to produce renin.

Many factors, including diuretics and many blood pressure medications, affect renin and aldosterone production. Assessing the ratio of renin in specimens collected from the two renal veins tends to normalize for most of these factors as long as there is a sufficiently high level of renin for adequate measurement.

What Lab Results Are Confirmatory?

Inappropriately high urine potassium concentration (>30 mmol/L) in the setting of low serum potassium provides evidence of high aldosterone. Urine sodium excretion is low. Renal artery sonography is a noninvasive imaging technique that can provide evidence of vascular stenosis.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

Catheterization of the renal vein to collect specimens for measurement of renin activity helps determine whether there is a unilateral lesion that may be responsive to surgical correction. Lateralization is usually considered to occur when the plasma renin from one renal vein is at least 1.5 times as much as from the other renal vein. Imaging studies and arteriography help identify whether there are structural disorders of kidneys or vascular obstructions. Many types of imaging techniques have been applied.

Diagnosis of renovascular hypertension has important implications for therapy for hypertension. Unilateral disease can be favorably treated surgically. Identification of atherosclerotic disease may lead to intensive medical therapy. Treatment of patients with renovascular hypertension with angiotensin converting enzyme inhibitors has led to improved outcome.