Hypertension, or high blood pressure, is a widespread condition with different underlying causes. One important subtype is Low Renin Hypertension (LRH), which affects approximately one-quarter of all people with high blood pressure. LRH is defined by elevated blood pressure despite the body having suppressed or abnormally low levels of the enzyme renin. In a healthy system, low renin signals that blood pressure is already high, so its suppression in a hypertensive patient suggests a problem with fluid and salt balance. Recognizing LRH is significant because its cause and the way it responds to standard medications differ from other forms of high blood pressure.
Understanding Renin and Aldosterone
The body regulates blood pressure and fluid levels through the complex Renin-Angiotensin-Aldosterone System (RAAS). Renin is an enzyme produced by the kidneys, typically released when blood pressure drops or salt levels are low. Renin acts on a protein to generate Angiotensin II, a potent hormone that constricts blood vessels and stimulates the adrenal glands.
This stimulation causes the adrenal glands to release aldosterone. Aldosterone acts primarily on the kidneys, prompting them to increase the reabsorption of sodium and water back into the bloodstream while simultaneously excreting potassium. This process raises the body’s fluid volume, which increases blood pressure.
In a healthy person, high blood pressure naturally suppresses renin release. LRH is defined by this suppression, where the body’s attempt to lower pressure is ineffective because the pressure remains high. This indicates that the high blood pressure is likely caused by an independent mechanism, often related to excessive salt and water retention, which is why LRH is often described as salt-sensitive hypertension.
Underlying Causes of Low Renin Hypertension
The most frequently identified cause of LRH is Primary Aldosteronism (Conn’s Syndrome). In this condition, one or both adrenal glands autonomously produce excess aldosterone, regardless of the body’s need. This excess forces the kidneys to retain too much sodium and water, expanding blood volume and leading to high blood pressure. The resulting elevated volume and pressure signal the kidneys to suppress renin production, creating the characteristic low renin and high aldosterone profile.
Non-Aldosterone Mineralocorticoid Excess Syndromes
LRH can also result from syndromes that mimic aldosterone’s action. One rare inherited form is Liddle Syndrome, where a genetic mutation causes the kidney’s epithelial sodium channels (ENaC) to become overactive. This leads to excessive sodium and water reabsorption, suppressing both renin and aldosterone levels (low renin, low aldosterone presentation). Another condition, Apparent Mineralocorticoid Excess (AME), occurs when an enzyme deficiency allows cortisol to inappropriately activate the aldosterone receptor, causing similar volume retention and hormone suppression.
Low-Renin Essential Hypertension
High salt intake alone can lead to LRH in many people, known as Low-Renin Essential Hypertension. Consuming a consistently high-sodium diet causes chronic volume expansion, which physiologically suppresses renin as the body attempts to excrete the excess salt and water. This form is a significant contributor to LRH, especially in older adults and certain ethnic groups.
Identifying Low Renin Hypertension
The diagnosis of LRH begins with blood tests measuring components of the RAAS: Plasma Renin Activity (PRA) and Plasma Aldosterone Concentration (PAC). PRA measures the active renin enzyme, while PAC measures aldosterone hormone. A low PRA confirms the low renin state, but the subsequent diagnosis depends on the PAC level.
If renin is low and aldosterone is inappropriately high, doctors screen for Primary Aldosteronism using the Aldosterone-to-Renin Ratio (ARR). A high ARR suggests that aldosterone production is independent of renin control, which is the hallmark of Primary Aldosteronism.
For accurate results, these blood tests require careful preparation, including the temporary withdrawal of certain blood pressure medications that can interfere with measurements. Factors like the patient’s posture and the time of day the blood is drawn must also be considered, as they naturally influence hormone levels. If initial screening suggests Primary Aldosteronism, further confirmatory tests are needed.
Targeted Treatment Approaches
Treatment for LRH is often more effective when it targets the underlying issue of volume and sodium retention, rather than the RAAS cascade itself.
Mineralocorticoid Receptor Antagonists (MRAs), such as spironolactone or eplerenone, are often a first choice, especially when Primary Aldosteronism is confirmed or strongly suspected. These medications block the effects of aldosterone on the kidney, preventing the reabsorption of sodium and water and promoting their excretion. This targeted action directly addresses the volume expansion driving the high blood pressure.
Diuretics, especially thiazide-type diuretics, are also highly effective in LRH because they reduce blood volume by directly increasing sodium and water excretion from the kidneys. Calcium Channel Blockers (CCBs) may also be used because they help relax blood vessels and work well in salt-sensitive forms of hypertension.
Standard blood pressure medications that target the RAAS, such as ACE inhibitors and Angiotensin Receptor Blockers (ARBs), are often less effective in LRH. This is because the renin system is already suppressed, meaning there is less of the target enzyme or hormone for these drugs to block. In rare cases, like Liddle Syndrome, specific treatment involves an epithelial sodium channel blocker, such as amiloride, which directly counteracts the genetic defect causing sodium retention.