Plasma renin activity explained

Plasma renin activity
Purpose:	measure of the activity of the plasma enzyme renin,

Plasma renin activity (PRA), also known as the renin (active) assay or random plasma renin, is a measure of the activity of the plasma enzyme renin, which plays a major role in the body's regulation of blood pressure, thirst, and urine output. Measure of direct renin concentration (DRC) is technically more demanding, and hence PRA is used instead.DRC assays are still in evolution, and generally a conversion factor of PRA (ng/mL/h) to DRC (mU/L) is 8.2. A recently developed and already commonly used automated DRC assay uses the conversion factor of 12.^[1] PRA is sometimes measured, specially in case of certain diseases which present with hypertension or hypotension. PRA is also raised in certain tumors.^[2] A PRA measurement may be compared to a plasma aldosterone concentration as an aldosterone-to-renin ratio (ARR).

Measurement and Values

Measurement is done from a sample of venous blood using immunological measuring mechanisms like ELISA, RIA, etc. Often these are done by automated machines to minimize human error.

Considerations for variation

Factors to take into account when interpreting results^[1]

• Age: in patients aged 65 years, renin can be lowered more than aldosterone by age alone, leading to raised ARR.
• Gender: premenstrual, ovulating females have higher ARR levels than age-matched men, especially during the luteal phase of the menstrual cycle, during which false positives can occur, but only if renin is measured as Direct renin concentration (DRC) and not as PRA (220).
• Time of day, recent diet, posture, and length of time in that posture
• State of water intake and hydration
• Salt intake
• Medications - Use of anti-hypertensive drugs, estrogen-containing forms of hormonal contraception, anti-anginals drugs, etc. (basically, most drugs that are active on the heart, blood vessels and/or the kidneys)
• Level of potassium
• Level of creatinine (kidney failure can lead to false-positive ARR)
• Certain diseases of the heart, kidneys, etc.
• Method of blood collection, including any difficulty doing so

Normal values

Reference ranges for blood tests of plasma renin activity can be given both in mass and in international units (μIU/mL or equivalently mIU/L, improperly shown as μU/mL or U/L, confusing mcU/mL used where Greek μ not available), with the former being roughly convertible to the latter by multiplying with 11.2.^[3] The following table gives the lower limit (2.5th percentile) and upper limit (97.5th percentile) for plasma renin activity by mass and MCU, with different values owing to various factors of variability of reference ranges:

Unit	Lower limit	Upper limit
ng/(mL*hour)	0.29,^[4] 1.9	3.7^[5]
μIU/mL	3.3, 21^[6]	41

Results and explanations

Please go through the physiology of renin and of the renin–angiotensin system to understand why the following occur.

Higher-than-normal levels may indicate:^{[7] [8] [9] [10] [11]}

Disease	Brief Description
	Kidneys trying to counter low aldosterone output.
Cirrhosis of the liver	RAAS activates as a compensatory response to the splanchnic arterial vasodilation due to portal hypertension
	Just more of renin is being secreted by the kidneys.
Hemorrhage (bleeding)	Kidneys trying to raise falling blood pressure.
	Kidneys trying to raise falling blood pressure due to reduced cardiac output.
	Excessive renin is being secreted by the kidneys.
	Tumors can secrete substances like this. See tumor markers
Renovascular hypertension	Renal vascular damage leading to reduced JGA perfusion.

Lower-than-normal levels may indicate:

Disease	Brief Description
ADH therapy	Leads to water retention and thus raised blood pressure.
Salt-retaining steroid therapy	see above
Salt-sensitive essential hypertension	see above
Primary Hyperaldosteronism	see above and direct inhibition of aldosterone on renin secretion

Further reading

• MedlinePlus Medical Encyclopedia(Public Domain - copy left):https://www.nlm.nih.gov/medlineplus/ency/article/003698.htm.
• Brenner & Rector's The Kidney, 7th ed., Saunders, 2004. pp. 2118–2119. Full Text with MDConsult subscription.

Notes and References

1. Web site: Primary Aldosteronism Guideline Resources.
2. Hamilton Regional Laboratory Medicine Program - Laboratory Reference Centre Manual. Renin Direct.
3. http://depts.washington.edu/labweb/referencelab/print/endo.pdf New Assays for Aldosterone, Renin and Parathyroid Hormone
4. Converted from values in μIU/mL by dividing with a factor of 11.2 μIU/mL per ng/(mL*hour), as given in:
   • New Assays for Aldosterone, Renin and Parathyroid Hormone University of

   Washington, Department of Laboratory Medicine. Retrieved Mars 2011

5. Pratt . R. . Flynn . J. . Hobart . P. . Paul . M. . Dzau . V. . Different secretory pathways of renin from mouse cells transfected with the human renin gene . The Journal of Biological Chemistry . 263 . 7 . 3137–3141 . 1988 . 10.1016/S0021-9258(18)69046-5 . 2893797. free .
6. Converted from values in ng/(mL*hour) by multiplying with a factor of 11.2 μIU/mL per ng/(mL*hour), as given in:
   • New Assays for Aldosterone, Renin and Parathyroid Hormone University of

   Washington, Department of Laboratory Medicine. Retrieved Mars 2011

7. Fujino T, Nakagawa N, Yuhki K, Hara A, Yamada T, Takayama K, Kuriyama S, Hosoki Y, Takahata O, Taniguchi T, Fukuzawa J, Hasebe N, Kikuchi K, Narumiya S and Ushikubi F. (2004) Decreased susceptibility to renovascular hypertension in mice lacking the prostaglandin I2 receptor IP. J. Clin. Invest. 114:805-812.
8. Human renin gene: structure and sequence analysis. 1984 Aug; PubMed Free text.
9. Cloning and sequence analysis of cDNA for human renin precursor. PubMed.
10. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. 2002 Jun; PubMed.
11. Different secretory pathways of renin from mouse cells transfected with the human renin gene. 1988 Mar 5; PubMed Free text.