The mystery of elevated renin

On May 29, 2024, the General Inspection Department of the Core Laboratory of the Shaanxi Xi'an Regional Medical Testing Center received a "Five Items of Hypertension (Upright)" test from a certain hospital. The test result of "Renin" was ">1000.00μIU/mL", which exceeded the upper limit of the reference range of this item by more than 20 times, and the other results were normal. This instantly attracted the attention of colleagues in the General Inspection Department, and they immediately re-examined according to standard operating procedures. The results were still the same after the re-examination. The patient's historical test records were then retrieved, and the "Five Items of Hypertension (Supine)" submitted by the patient on May 27 was found in the system, and the "Renin" result was 50.53μIU/mL.

Although different body positions have an impact on the results of the "renin" test, how can the results differ by more than 20 times? This caused colleagues in the general inspection department to think and start looking for the cause.

After excluding influencing factors during the test, such as instrument status, indoor quality control, and personnel operation, is it possible that it is caused by pre-test factors? Common pre-test factors that affect renin results include collection, transportation, and patient preparation.

01 Specimen collection and transportation:

"Renin", as an important component of the renin-angiotensin system, is a proteolytic enzyme released by the juxtaglomerular cells of the renal juxtaglomerular apparatus. It exists in the human body in three forms: inactive prorenin, active prorenin, and renin. The latter two have renin activity, but at 2-8°C, the inactive prorenin will be cold-activated and converted into renin, resulting in a false increase in the renin test results. This situation is also one of the important factors for false increase in renin in clinical tests.

Taking into account the effect of cold activation on renin, although it has been confirmed that the collection and logistics transportation are strictly carried out in accordance with relevant regulations, in order to eliminate the influence of this factor, colleagues from the General Inspection Department promptly contacted the sending unit to re-collect the specimens from the same position when the patient is calm. After mixing, the plasma was promptly centrifuged and separated and frozen at -20°C for inspection.

On May 31, the laboratory received the frozen specimens and performed standard operations. The results of two retests on the machine were the same as on the 29th, both >1000.00μIU/mL, excluding the influence of "cold activation" on the results.

02 Patient preparation:
The impact of drugs on renin test results is also extremely critical. The "Expert Consensus on the Diagnosis and Treatment of Primary Aldosteronism (2020 Edition)" [1] clearly states that angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), calcium ion antagonists (CCB) and other drugs can cause false increases in renin results, while having little effect on other results.

After communicating with the clinic, the patient was admitted to the hospital for "hypertension" on May 26, and was prescribed oral "Irbesartan" (an angiotensin receptor antagonist (ARB) antihypertensive drug) on ​​May 27. The specimens sent for examination on May 27 were before taking the medicine, and the specimens sent for examination on May 29 and 31 were after taking the medicine. The expert consensus clearly pointed out that such drugs can significantly increase the renin test results, resulting in false positive results; the drug must be discontinued for at least two weeks before primary aldosteronism (ARR) testing can be performed.

Finally, it was determined that the patient's "renin" result was a false increase caused by the drug. After communicating with the clinician, the doctor agreed with this conclusion and praised the professional level of the General Inspection Department of Xi'an Regional Medical Laboratory Center.

This case also triggered the laboratory technicians' thinking: in clinical testing, we must always pay attention to the "patient's medication history before testing" to avoid the impact of test results caused by drug interference on clinical diagnosis and treatment.

According to the "China Cardiovascular Health and Disease Report 2022" [2], "hypertension" has become the top risk factor for cardiovascular disease. According to statistics, as of 2019, there were about 109 million registered hypertensive patients in China, and the standardized management rate of hypertensive patients increased by 29.28% compared with 2009. The gap in the standardized management rate of hypertensive patients in the east, central and western regions has gradually narrowed; the blood pressure control rate of the hypertensive population under management has increased from 50.88% in 2009 to 67.72% in 2019. However, due to the large patient base, there are still a large number of hypertensive patients who are not managed.

The general inspection department of the core laboratory of Xi'an Regional Medical Testing Center uses a fully automatic chemiluminescence analyzer to detect hypertension-related items such as renin, angiotensin II, aldosterone, cortisol, adrenocorticotropic hormone, etc., which can assist in the diagnosis of the causes of secondary hypertension, thereby assisting and guiding clinical scientific diagnosis and treatment.