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High Renin Causes, Symptoms, Management & Genetics

Written by Ana Aleksic, MSc (Pharmacy) | Last updated:
Puya Yazdi
Medically reviewed by
Puya Yazdi, MD | Written by Ana Aleksic, MSc (Pharmacy) | Last updated:

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High blood pressure is a common health concern, and it may point to abnormal renin. Produced by the kidneys, this enzyme helps control blood pressure and fluid balance. Without renin, we would not be able to maintain blood pressure when we lose salt. Both high and low levels of renin may underlie high blood pressure, but this post focuses specifically on high renin.

What is Renin?

Definition

Our bodies maintain a delicate balance with blood pressure in order to deliver appropriate amounts of oxygen and nutrients to every cell in the body. Because we are regularly flooding our blood with chemicals that shift this balance, the control is dynamic [1, 2].

One way the body exerts this control is through renin, an enzyme responsible for initiating a cascade of events in response to low blood pressure. These events are collectively controlled by the renin-angiotensin system (RAS) [1, 2].

Blood Test

Renin is most commonly measured as plasma renin activity (PRA), or “active renin”. Plasma renin activity is a measure of the capacity of renin to generate angiotensin I (precursor of angiotensin II) [1].

Another method is measuring plasma renin concentration (PRC, pg/ml). Compared to PRA, PRC is faster, easier to perform, and reproducible. However, unlike PRA, it is not sensitive in measuring low levels of renin [3+, 4+].

High Levels

Lab results are commonly shown as a set of values known as a “reference range”, which is sometimes referred to as a “normal range”. A reference range includes the upper and lower limits of a lab test based on a group of otherwise healthy people.

Your healthcare provider will compare your lab test results with reference values to see if any of your results fall outside the range of expected values. By doing so, you and your healthcare provider can gain clues to help identify possible conditions or diseases.

Normal plasma renin activity levels range from 0.25 – 5.82 ng/mL/hr. Values above this range are considered high.

Normal ranges may vary among different labs.

Some lab-to-lab variability occurs due to differences in equipment, techniques, and chemicals used. Don’t panic if your result is slightly out of range — as long as it’s in the normal range based on the laboratory that did the testing, your value is normal.

However, it’s important to remember that a normal test doesn’t mean a particular medical condition is absent. Your doctor will interpret your results in conjunction with your medical history and other test results.

Have in mind that a single test isn’t enough to make a diagnosis. Your doctor will interpret this test, taking into account your medical history and other tests. A result that is slightly low/high may not be of medical significance, as this test often varies from day to day and from person to person.

High Renin

Causes

Causes shown here are commonly associated with high renin. Work with your doctor or other health care professional for an accurate diagnosis.

1) Menstrual Cycle Phase

Renin activity levels increase during the luteal phase of a menstrual cycle in women [5+].

2) Dehydration

In a study of 10 people, plasma renin activity increased with decreased blood volume due to dehydration [6+].

3) Upright Body Posture

An upright body posture slightly decreases blood pressure, which stimulates renin production. One study in 10 people found that assuming an upright posture increased plasma renin activity [6+].

4) Pregnancy

The renin-angiotensin system (RAS) is more active during pregnancy. In early pregnancy, the kidneys produce more renin and the ovaries and uterine lining produce an inactive renin precursor (prorenin). Also, as the placenta grows, it produces estrogen, which increases angiotensinogen production by the liver, leading to increased blood angiotensin II [7, 8, 9].

Because of an increase in aldosterone and other hormonal changes, pregnant women have higher blood volume [10].

5) Stress

Stress increases sympathetic activity, which stimulates renin production. In a study of 20 people (10 with high blood pressure, 10 healthy), mental stress increased plasma renin activity in both groups [11, 12].

6) Strenuous Exercise

In a study of 33 runners, plasma renin activity increased 3-fold after a marathon run [13].

7) Hyperthyroidism

Plasma renin activity levels were elevated in 24 people with hyperthyroidism (likely due to increased sympathetic activity) [14].

8) Addison’s disease

Adrenal glands that do not make enough aldosterone and other hormones (e.g Addison’s disease or other adrenal gland insufficiencies) can cause elevated renin activity levels [15].

This is because a lack of aldosterone leads to increased sodium excretion, which lowers blood sodium levels and subsequently, blood volume and pressure. This drop in blood sodium levels activates renin production in the kidney [15].

9) Low Blood Volume

Low blood volume activates renin production. Conditions that lead to low blood volume include:

  • Bleeding (hemorrhage) [16, 17]
  • Heart failure [15]
  • Nephrotic syndrome (a kidney disorder that causes excess protein in the urine) [18]

10) Renal Artery Stenosis

Renal artery stenosis, or the narrowing of one or both of the arteries that carry blood to the kidneys, decreases kidney blood flow. This drop in blood flow stimulates renin production [19, 20].

Hardening of the arteries (atherosclerosis) is the most common cause of renal artery stenosis [20].

11) Malignant Hypertension

Malignant hypertension is defined as sudden and very high blood pressure that causes organ damage.

In a study of 30 people with malignant hypertension (n=18) and severe hypertension (n=12), plasma renin activity and aldosterone levels were significantly elevated in those with malignant hypertension but not in severely hypertensive people despite minimal differences in blood pressure [21].

This may occur due to the damage of small kidney blood vessels caused by severe hypertension, which results in reduced blood flow in the kidneys. This activates renin production, which in turn may result in further blood vessel damage [21].

12) Reninoma

Reninomas are rare tumors of the kidney cells that make renin (juxtaglomerular cell tumors). They produce excessive amounts of renin, resulting in severe hypertension, high aldosterone levels, and low blood potassium levels [22, 23].

13) Liver Scarring

Liver scarring (cirrhosis) promotes fluid buildup within the abdomen (ascites). This leads to decreased circulating blood volume, which stimulates renin production [24].

14) Pheochromocytoma

Pheochromocytoma is a rare, usually benign tumor that develops in the adrenal gland. It causes the adrenal gland to make too many hormones (catecholamines).

In a study of 7 people with pheochromocytoma, plasma renin activity remained high after suppression with saline in 4 people and decreased into the normal range in all 4 people after surgical removal of pheochromocytoma [25+].

15) Certain Drugs

Drugs that may increase plasma renin activity levels include [26, 27, 28]:

  • Diuretics
  • Dihydropyridine calcium channel blockers
  • Hydralazine
  • Angiotensin-converting enzyme (ACE) inhibitors
  • Angiotensin receptor antagonists

Please discuss your medications with your doctor.

Associations

The following diseases have been associated with higher renin levels. However, there is no evidence to suggest that high renin levels will directly cause these diseases.

Even if a study did find that high renin can contribute to a disease or health outcome–for example, heart disease or dying–high renin is highly unlikely to be the only cause.

Complex chronic disorders like heart disease always involve multiple possible factors — including brain chemistry, environment, health status, and genetics — that may vary from one person to another.

1) Risk of Dying

Higher plasma renin levels were associated with the risk of dying from all causes in an observational study of 3200 people (1413 with high blood pressure) [29].

2) Heart Disease

Higher plasma renin activity levels were associated with a greater risk of heart attacks (regardless of blood pressure) in a study of 1717 people with mild to moderate hypertension [30].

Plasma renin concentration was associated with long-term mortality due to heart disease in 3303 patients referred to coronary angiography (x-ray imaging to examine the blood vessels of the heart) [31].

3) Obesity

Plasma renin activity and angiotensin-converting enzyme (ACE) correlate with BMI in obese people [32+, 33+, 34].

4) Chronic Kidney Disease (CKD)

Higher levels of PRA are associated with greater rates of CKD in 9500 people (the majority with high blood pressure) [35+].

Management of High Renin Levels

Addressing Underlying Health Conditions

If you have high renin levels, your doctor will recommend treatment and monitoring based on the underlying cause.

Drugs that are used to treat certain underlying health conditions that also decrease renin activity levels include [36, 37+]:

  • Certain drugs that treat high blood pressure (e.g. beta-blockers, clonidine, alpha-methyldopa)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) and COX-2 inhibitors
  • Heparin (a drug that treats blood clots)
  • Vasopressin

Your doctor will prescribe appropriate drug therapy based on the underlying cause of your high renin levels and other symptoms.

The following conditions must be resolved in order to normalize renin levels:

a) Hyperthyroidism

Some treatment options include [38+, 39+]:

  • Radioiodine ablation, which destroys thyroid cells, and therefore lowers thyroid hormones
  • Thyroidectomy (surgical removal of the thyroid)
  • “Antithyroid” medications such as Tapazole (methimazole) and propylthiouracil (which stop thyroid hormone synthesis) or cholestyramine (which promotes excretion of excess thyroid hormones)
  • Beta-blockers like propranolol, atenolol, and nadolol can be taken to ease hyperthyroid symptoms

b) Addison’s Disease

Hormone replacement therapy is used to correct for deficient levels of cortisol and aldosterone [40+, 41+, 42].

c) Renal Artery Stenosis

Treatment mainly consists of controlling high blood pressure with drugs/lifestyle changes [43+].

If hardening of the arteries (atherosclerosis) is the underlying cause, drugs that lower cholesterol may be prescribed [44].

For more severe cases, surgery is used to restore blood flow to the kidneys [43].

d) Reninoma

Drugs that lower blood pressure may be prescribed to reduce symptoms [23].

Surgically removing the tumor restores normal blood pressure in a majority of patients with reninoma [23].

e) Pheochromocytoma

The main treatment for pheochromocytoma is surgery to remove the tumor, which usually results in a cure [45+, 46].

f) Liver Scarring (Cirrhosis)

Aside from medication, people with liver scarring (cirrhosis) can discuss the following complementary approaches for supporting liver health with their doctor :

  • Limiting alcohol intake – excess alcohol can damage liver cells and worsen existing liver conditions [47]
  • Eating a well-balanced diet [48]
  • Drinking moderate to high (>3 cups) amounts of coffee (regardless of caffeine content) on a regular basis [49, 50+]
  • Getting more quality sleep [51+]
  • Eating more foods that are thought to help detox the liver and kidneys such as asparagus, cabbage, and broccoli [52]
  • Drinking more water [52]
  • Buying organic meats and vegetables to avoid chemical additives and pesticides [53]

The effectiveness of most of these approaches is unknown, though.

Some drugs or supplements can damage the liver. Have a doctor or pharmacist review your medications to see if any could be harmful to the liver [54, 55].

What to Have in Mind

This list is not exhaustive.

Once the underlying cause of low levels is under control, you may talk to your healthcare provider about lifestyle changes and complementary approaches that may help.

Below are some approaches to bring up with your doctor. These are typically recommended to people with low renin and high blood pressure.

Complementary Approaches

You may try the diet- and lifestyle-based interventions discussed below if you and your doctor determine that they could be appropriate.

Remember that these complementary approaches should ever be done in place of what your doctor recommends or prescribes.

Stay Hydrated

Drinking enough water and making sure you are well hydrated, which helps increase blood volume, and in turn decrease renin [6+].

Manage Stress Levels

Because stress can raise renin levels, managing your stress levels may help. Techniques that have been suggested to help reduce stress include [56, 57, 58, 59, 60, 61, 62+]:

Gene Mutations and High Renin

Research Limitations

The following genetic conditions are associated with high renin levels.

It’s important to note that just because certain genotypes are associated with a disease, it doesn’t necessarily mean that everyone with that genotype will actually develop the disease!

Many different factors, including other genetic and environmental factors, can influence the risk of abnormal renin levels.

Associated Conditions

1) Bartter’s Syndrome

Bartter’s syndrome is a rare inherited defect of the kidney cells in the part of the kidney that reabsorbs electrolytes (loop of Henle) and is characterized by [63+]:

  • High blood renin levels
  • Potassium wasting
  • Low blood chloride levels
  • Metabolic alkalosis (high blood pH)
  • High aldosterone secretion
  • Normal blood pressure
  • High urine prostaglandin levels
  • Frequent need to drink and urinate

The syndrome is caused by mutations in the Na+/K+/2Cl– cotransporter 2 (NKCC2), as well as in the following related proteins [64+]:

  • ROMK (a protein that moves potassium out of the cells)
  • ClC-Kb (a protein that moves chloride out of the cells)
  • CaSR (a protein that detects calcium levels and uses them as a signal to activate electrolyte transporters)

2) Gitelman’s Syndrome

Gitelman’s syndrome is a hereditary disease with similar symptoms to Bartter’s (metabolic alkalosis with low potassium, low chloride, high renin, and high aldosterone levels in the blood), but due to defects in the kidney cells of a different region (distal convoluted tubule). The condition is caused by mutations in the Na+/Cl– cotransporter (NCCT) [65+, 66+, 36].

Learn More

About the Author

Ana Aleksic

Ana Aleksic

MSc (Pharmacy)
Ana received her MS in Pharmacy from the University of Belgrade.
Ana has many years of experience in clinical research and health advising. She loves communicating science and empowering people to achieve their optimal health. Ana spent years working with patients who suffer from various mental health issues and chronic health problems. She is a strong advocate of integrating scientific knowledge and holistic medicine.

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