Hypertension, or high blood pressure, is not a one-size-fits-all diagnosis. A subtype known as low-renin hypertension accounts for up to 30% of cases and is characterized by low levels of a kidney-produced enzyme called renin, even while blood pressure remains elevated. This low renin level provides a clue about the underlying mechanism driving the condition. It suggests that another factor is maintaining the hypertension, prompting the body to try and lower it. Understanding this profile is necessary for identifying the cause and tailoring an effective treatment plan.
The Role of Renin and Aldosterone in Blood Pressure
The body’s blood pressure is regulated by the Renin-Angiotensin-Aldosterone System (RAAS). This system acts like a thermostat, initiating actions to raise blood pressure when it drops too low. The process begins in the kidneys, which monitor blood flow and release the enzyme renin into the bloodstream if pressure falls.
In circulation, renin converts a liver-produced protein, angiotensinogen, into angiotensin I. Angiotensin I is then acted upon by another enzyme to become angiotensin II, a hormone that constricts blood vessels to increase blood pressure.
Angiotensin II also travels to the adrenal glands, located on top of the kidneys, and instructs them to release the hormone aldosterone. Aldosterone signals the kidneys to retain more sodium, and water follows sodium, increasing the total volume of fluid in the bloodstream. This increase in blood volume further elevates blood pressure.
Once blood pressure returns to a normal level, a feedback loop signals the kidneys to stop releasing renin. In low-renin hypertension, this system is suppressed because high blood pressure from other causes is already present. The body keeps renin levels low to counteract the high pressure, but this response is overridden by the primary driver of the hypertension.
Underlying Causes and Risk Factors
The most common cause of low-renin hypertension is primary aldosteronism, also known as Conn’s syndrome. This disorder occurs when one or both adrenal glands produce too much aldosterone independently of the RAAS, which drives up blood pressure. In response, the kidneys suppress renin production.
Primary aldosteronism is frequently caused by a small, noncancerous tumor (adenoma) on one adrenal gland. Another cause is bilateral adrenal hyperplasia, a condition where both glands become enlarged and overproduce aldosterone. Less commonly, the condition can run in families due to gene mutations.
High dietary salt intake is another contributor. For salt-sensitive individuals, a high-sodium diet increases fluid retention and blood volume, which in turn suppresses renin. This form is often called low-renin essential hypertension when no single secondary cause can be identified.
Demographic factors also play a role, as renin levels naturally decrease with age, making older adults more susceptible. The condition is also more common in individuals of African descent. In rare cases, genetic disorders like Liddle syndrome can mimic the effects of excess aldosterone.
Diagnosis and Testing
The diagnostic process for low-renin hypertension begins with a high blood pressure reading, particularly if the condition is difficult to control. Confirmation requires blood tests that measure the hormones involved in the RAAS.
The initial tests measure plasma renin and aldosterone concentrations in the blood. These are performed together to evaluate the relationship between the two hormones. In low-renin hypertension, the defining feature is a suppressed renin level despite high blood pressure.
To screen for primary aldosteronism, clinicians calculate the aldosterone-to-renin ratio (ARR). A high ARR, indicating that aldosterone levels are high relative to the low renin levels, is a strong indicator of the condition. This ratio is the most reliable screening tool for differentiating primary aldosteronism from other causes of hypertension.
If the ARR is elevated, further confirmatory testing may be necessary. This can include a saline suppression test to see if the adrenal glands properly reduce aldosterone production. Imaging tests, such as a CT or MRI scan of the adrenal glands, are also used to look for a tumor or enlargement.
Targeted Treatment Approaches
A correct diagnosis of low-renin hypertension guides treatment, as common medications like ACE inhibitors and ARBs are less effective. These drugs target the RAAS, which is already suppressed in this condition, so they have little to act upon and often fail to lower blood pressure.
The most effective pharmacological treatments target the source of the problem: the effects of excess aldosterone. Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, are a mainstay of therapy. These medications work by blocking the receptors that aldosterone binds to, preventing it from signaling the kidneys to retain salt and water.
Other classes of blood pressure medications can also be effective. Thiazide diuretics are a useful option as they help the body excrete excess sodium and water. Calcium channel blockers, which relax and widen blood vessels, are another alternative that can successfully lower pressure in this condition.
Lifestyle modifications are a component of managing low-renin hypertension, regardless of the cause. A low-sodium diet is particularly important, as restricting salt intake helps reduce water retention and complements medication. In cases where an adrenal tumor is identified, surgical removal of the affected gland can provide a cure.