Improved immunoradiometric assay for plasma renin

Background: Our renin IRMA overestimated renin in plasmas with high proreni n-to-renin ratios. We suspected that the overestimation of renin was caused less by cross-reactivity of the renin-specific antibody with prorenin than by a conformational change of prorenin into an enzymatically active form d uring the assay. Methods: Because the inactive form of prorenin converts slowly into an acti ve form at low temperature, we raised the assay temperature from 22 degrees C to 37 degrees C, simultaneously shortening the incubation time from 24 t o 6 h. The former IRMA was performed in <1 working day with these modificat ions. Results: The comeasurement of prorenin as renin was eliminated. Reagents we re stable at 37 degrees C, and the new and old IRMAs were comparable in ter ms of precision and accuracy. The functional lower limit of the assay (4 mU /L) was below the lower reference limit (9 mU/L). The modified IRMA agreed closely with the activities measured with an enzyme-kinetic assay. Results were not influenced by the plasma concentration of angiotensinogen. At norm al angiotensinogen concentrations, the IRMA closely correlated with the cla ssical enzyme-kinetic assay of plasma renin activity. Conclusion: The modified IRMA, performed at 37 OC, avoids interference by p rorenin while retaining the desirable analytical characteristics of the old er IRMA and requiring less time. (C) 1999 American Association for Clinical Chemistry.