Analytical Variation in Plasma Renin Activity: Implications for the Screening of Primary Aldosteronism

Extract

To the Editor:

The Editorial by Stowasser and Gordon recently published in Clinical Chemistry is commendable (1). We fully agree with their reservations on the use of commercial assays by inexperienced laboratories and their point that patient management decisions should not be based on a single measurement of the ratio of aldosterone to plasma renin activity (ARR). We would like to reinforce this point by demonstrating the important influence of analytical variation on ARR measurement results.

Plasma renin activity (PRA) is evaluated as the difference in angiotensin I production by the enzyme at 37 °C and endogenous angiotensin I, estimated by a determination of angiotensin I at 4 °C. Therefore the CV of the assay is determined by the variations of the measurements at 37 °C and 4 °C.

To evaluate the impact of these assay variations on the ratio results, we performed 5 PRA determinations during a 5-week period on 2 samples with activities of ∼0.6 and ∼0.7 μg/L/h. The samples were divided into aliquots and kept at −80 °C until analysis. Using the RENCTK reagent set (Diasorin) according to the manufacturer’s instructions, 4 well-trained and experienced technicians (with an average work experience of 26.8 years) performed the tests along with routine PRA determinations. The results are presented in Table 1¹ .