ObjectivesThe measurement of plasma renin activity (PRA) is very convenient for estimating the action of the renin system, but its interlaboratory reproducibility is notoriously poor. This multicentre study aimed to examine whether an immunoradiometric assay which quantifies renin directly with monoclonal antibodies can reduce this limitation of the enzymatic assay. The study also aimed to establish the reference values of immunoreactive renin (IrR) in a large sample of normotensive subjects and patients with various pathophysiological conditions.Design and methodsPRA and IrR were measured once in each of the eight participant centres in eight pool plasma samples with a wide range of renin content; in seven centres these measurements were repeated twice more in order to compare the intralaboratory interassay reproducibility of both methods. Finally, PRA and IrR were measured in the supine and standing positions in 503 subjects including normal controls, patients with various forms of hypertension, patients with Cushing's and Banter's syndromes, patients with hepatic cirrhosis and pregnant women.ResultsWe found that both the inter- and intralaboratory coefficients of variation for PRA measurements were higher than those for IrR. In plasma samples from normal subjects and from patients, mean±SEM supine PRA and IrR ranged, respectively, from 0.08±0.03 ng/ml per h and 2.6±0.5 pg/ml in patients with Conn's syndrome to 7.2 ±2.5 ng/ml per h and 138±51 pg/ml in patients with hepatic cirrhosis. PRA and IrR were found to be significantly correlated in all laboratories (mean±SEM of correlation coefficients 0.8410.03) and for all of the conditions (correlation coefficient ranging from 0.98 in patients with Cushing's syndrome to 0.50 in pregnant women). However, for the pregnant women the slope of the regression line depicting the PRA-IrR relationship was significantly steeper than for all of the other conditions.ConclusionsIn our experience the inter- and intralaboratory reproducibilities of the immunoradiometric assay appear to be greater than can be achieved with the enzymatic assay, the difference being probably due to the greater complexity of the latter. The two methods provide superimposable information on the renin-angiotensin system activity, except in pregnancy, during which the PRA: IrR ratio is much higher than in the other conditions. Therefore, in this and other pathophysiological situations associated with marked angiotensinogen concentration alterations, the enzymatic assay may be still preferable for assessing the activity of the system accurately.