RENIN

Preferred Sample Type

Renin

Suitable Specimen Types

  • EDTA Plasma
Min 0.3 mL

Sample Processing in Laboratory

Samples MUST NOT be transported on ice.

Samples should be transported to the lab ASAP (and within four hours of collection) at room temperature.

Sample Preparation

After collection, centrifuge samples immediately, at room temperature and store plasma aliquot at -20°C. Do NOT chill sample collection tubes or store collection tubes on ice.

Turnaround Time

7 days

Sample Stability

-20°C

Renin

General Information

Renin is an enzyme that belongs to the family of aspartyl proteases, which was first discovered to be synthesised in the juxtaglomerular cells of the kidney. At present there is evidence that renin synthesis can also occur in other organs such as brain, heart and arterial smooth muscle. Renin circulates in two different forms, prorenin and the active renin forms. Prorenin is the enzymatically inactive biosynthetic precursor of renin.

Renin is substrate specific and is capable of converting circulating angiotensinogen into biologically inactive decapeptide angiotensin I. Angiotensin I in turn is converted to the octapeptide angiotensin II by means of the angiotensin converting enzyme (ACE). ACE is located on the endothelium and smooth muscle cells of the blood vessels from the kidney, lung and many other organs. Renin substrate, angiotensin I and II and ACE are collectively known as the renin angiotensinogen system or RAS. Under normal conditions and in many pathological situations it is the amount of renin secreted by the kidney that determines the activity of the whole system.

Measurement of plasma renin is therefore a good index of RAS activity. Renin secretion is increased when blood pressure in the arterioles is low and by sympathetic stimulation. RAS is activated by haemorrhagic and cardiogenic shock, after fluid loss by diarrhoea and the use of diuretics, and in oedematogenic conditions such as liver or kidney disease. The RAS is also activated in patients with stenosis of the renal artery, in such patients it is partly responsible for the development of hypertension.

Autonomous, angiotensin II independent hypersecretion of aldosterone, as in adrenal tumour, also leads to hypertension. In such cases plasma renin is low, opposed to secondary aldosteronism where the hypersecretion of aldosterone is caused by angiotensin II. In most patients with primary or essential hypertension the cause of the hypertension is unknown. Plasma renin levels in these cases are normal or low. Within a subgroup of patients with essential hypertension, plasma renin is high. These patients have a higher risk for stroke and myocardial infarction. The clinical utility of plasma renin assays is mainly centred around the diagnosis and management of patients with hypertension due to renal artery stenosis or renovascular hypertension. Renin assays can also help the clinician decide whether or not to perform X-ray studies of the renal blood vessels.

Renin assays are also increasingly important for the diagnosis of primary aldosteronism and has been recommended to be used to calculate the aldosterone/renin ratio3. Surgical removal of the adrenal tumour will often cure the hypertension; however in bilateral hyperplasia drug therapy may be required. Not only can the renin assay help provide information on the risk of cardiovascular complications in patients with essential hypertension but they are also used in the management of patients with adrenal insufficiency receiving steroid therapy substitution. With insufficient substitution, plasma renin is high; with adequate therapy, plasma renin will be normal.

 

 

 

Patient Preparation

Attempt to correct any hypokalaemia and patients should be on a liberal rather than restricted sodium intake.

Withdraw the following agents that may affect aldosterone/renin ratio (ARR) for at least 4 weeks:

  • Spironolactone, eplerenone, amiloride and triamterene
  • Potassium-wasting diuretics
  • Products derived from liquorice root (e.g. Confectionary liquorice, chewing tobacco)

If the ARR off the above agents are not diagnostic, and if hypertension can be controlled with relatively non-interfering medications, withdraw other medications that may affect the ARR for at least 2 weeks:

  • Beta-adrenergic blockers, central alpha-2 agonist (e.g. clonidine, alpha-methyldopa), nonsteroidal anti-inflammatory drugs
  • Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, renin inhibitors, dihydropyridine calcium antagonists

If necessary to maintain hypertension control, commence other hypertensive medications that have a lesser effects on ARR (e.g. verapamil slow release, hydralazine, prazosin, doxazosin, tetrazosin).

Establish oral contraceptive (OC) and hormone replacement therapy (HRT) status, as oestrogen containing medications may lower direct Renin concentrations and cause false positive ARR.  Do not withdraw OC unless confident of alternative contraception.

Blood samples should be drawn in the morning.

Please note on the request form the position of the patient at sampling as this will allow the appropriate reference range to be used. The patient should remain recumbent for 15 mins (or more) prior to collection of the supine sample. The patient should be upright for at least 15 mins before the ambulatory sample is taken.

For aldosterone/renin ratio, patient needs to be seated for 5-15 minutes before taking blood.  Collect blood mid-morning, after the patient has been up (sitting, standing, or walking) for at least 2 hours.  Please note on the request form the position of the patient at sampling.

Notes

Haemolysed and lipaemic samples are unsuitable for analysis. Freezing and thawing of plasma samples should be avoided.

Please contact laboratory for more information if required.

1. Collect blood mid-morning, after the patient has been up (sitting, standing, or walking) for at least 2 hours and seated for 5-15 minutes. 2. Collect blood carefully, avoiding stasis and haemolysis. 3. Maintain sample at room temperature (and not on ice, as this will promote conversion of inactive renin to active renin) during delivery and prior to centrifugation.

 

Reference Range

Adult supine 9.8-23.8 mU/L, Adult ambulatory 12.9-33.7 mU/L.

Aldosterone/renin ratio <71pmol/mU  - Primary Aldosteronism (Conn’s syndrome) unlikely but interpret with caution as ratio affected by medication. The Aldosterone/Renin ratio cut-off that we are providing is a guide only and not a diagnostic test and the ratio should be interpreted, cautiously, in conjunction with relevant clinical information and medications that may affect the ratio.

From 1/3/18 samples will be analysed using IDS iSYS direct renin mass immunoassay which will use the following reference ranges:

Ambulatory:  Female: 6.1 – 62.7 mIU/L,  Male: 9.0 – 103 mIU/L

Supine: 4.2 – 59.7 mIU/L

Screen positive for Conns: Aldosterone/renin ratio >91pmol/mU + aldosterone >750 pmol/L

(Endocrine guidelines on the investigation of Conns https://academic.oup.com/jcem/article/93/9/3266/2596343)

Specifications

  • EQA Scheme?: Yes
  • EQA Status: RIQAS

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