What is renin?
Renin is an enzyme produced in the juxtaglomerular cells of the kidneys and acts as the starting point of the body's blood pressure and fluid regulation system, the RAAS (renin–angiotensin–aldosterone system). Renin is released when the kidneys perceive that blood pressure is too low, blood volume is decreasing, or when the sodium content in the kidney filtrate is falling. By activating the RAAS, renin affects both blood pressure, blood volume, and salt balance.
How is renin controlled in the body?
Renin is produced in the juxtaglomerular cells of the kidneys, which function as both pressure and salt sensors. These cells register changes in blood pressure, blood flow, and sodium content and adjust renin release accordingly to keep blood pressure and circulation as stable as possible.
- Low blood pressure or reduced blood flow to the kidneys.
- Low sodium levels in the distal tubules of the kidneys.
- Activation of the sympathetic nervous system (e.g. during stress or physical exertion).
These signals cause the kidneys to increase renin secretion to restore the body's balance by activating the RAAS system.
What does renin do in the body?
Renin starts the RAAS chain by converting the protein angiotensinogen (produced in the liver) into angiotensin I. This is then converted further into angiotensin II, a hormone that constricts blood vessels and thereby raises blood pressure, stimulates the adrenal glands to release aldosterone and causes the kidneys to reabsorb more sodium and water. Together, this leads to increased blood volume and stabilization or elevation of blood pressure when the body needs it. In this way, renin is one of the body's most important markers for understanding how blood pressure and fluid balance are regulated.
Why is P-Renin measured?
P-Renin is primarily used in the investigation of high blood pressure, especially when a hormonal cause is suspected. Renin is almost always analyzed together with aldosterone, since their relationship is crucial for diagnosis. Renin is a central component in the calculation of the aldosterone/renin ratio (ARR ratio), which is the first-line method for screening for primary hyperaldosteronism (Conn's syndrome). The ratio helps doctors determine whether aldosterone production is abnormally high in relation to renin.
Measurement of renin is also valuable in secondary hypertension, kidney disease and in disorders of potassium balance.
Common indications for testing P-renin
- Investigation of high blood pressure with suspicion of hormonal influence
- Rapid onset or difficult-to-treat hypertension
- Unclear disorders in potassium (low or high potassium)
- Suspected renovascular hypertension (e.g. renal artery stenosis)
- Suspected disorders of the RAAS system
Note that renin is often interpreted in relation to aldosterone. The combination of both tests provides the clearest diagnostic picture.
What can cause a high renin level?
An elevated renin level is seen when the body tries to increase blood pressure or blood volume by activating the RAAS system. Common causes are:
- Renovascular disease (e.g. renal artery stenosis)
- Heart failure
- Chronic kidney disease
- Low blood pressure, dehydration or blood loss
High renin together with high aldosterone may indicate secondary hyperaldosteronism, while high renin and low aldosterone may occur in adrenal insufficiency.
What can cause low renin?
Low renin is seen primarily when aldosterone is produced in excess independently of the RAAS system, such as in primary hyperaldosteronism (Conn's syndrome). Renin can also be low in:
- Renal insufficiency where renin-producing tissue is damaged
- Long-term high salt intake
- Effects of certain medications, e.g. beta blockers
Symptoms and clinical signs associated with impaired renin
Impaired renin levels themselves do not cause any direct symptoms, but the underlying conditions can cause:
- High or difficult-to-treat blood pressure
- Low potassium – fatigue, muscle weakness, cramping sensations
- Dizziness or drop in blood pressure
- Signs of kidney or heart disease
Aldosterone/Renin Ratio (ARR) – why is it important?
The ARR ratio compares the level of aldosterone to the level of renin. It is the primary screening test for primary hyperaldosteronism.
- High aldosterone + low renin → high ARR ratio → suspicion of primary hyperaldosteronism
- High renin + high aldosterone → secondary hyperaldosteronism
- Low aldosterone + high renin → possible adrenal insufficiency
Interpretation must always be related to the conditions of the sample collection, medications and salt intake.
Sample collection and important preparations for P-Renin
Renin is affected by several factors, which makes standardized sampling important:
- Samples are usually taken in the morning
- Body position should be documented – different reference intervals apply for lying and standing
- The patient should have stood/walked for approximately 30 minutes before a standing test
- P-Renin is analyzed from the same tube as P-Aldosterone
Renin is affected by salt intake and many blood pressure medications such as beta-blockers, ACE inhibitors, ARBs, spironolactone, eplerenone and diuretics. Licorice can also give falsely low renin values.
Reference intervals for Renin
The reference intervals vary between laboratories and depend on body position and analysis method. Always compare with your specific test result.
The interpretation is often based on:
- The renin level in relation to aldosterone
- The ARR ratio
- Potassium value
- Clinical picture, blood pressure and possible comorbidities