CLINICAL VALIDATION OF RENIN MONOCLONAL ANTIBODY-BASED SANDWICH ASSAYS OF RENIN AND PRORENIN, AND USE OF RENIN INHIBITOR TO ENHANCE PRORENIN IMMUNOREACTIVITY

Newly developed IRMAs to measure the plasma concentrations of renin an d prorenin were validated for clinical use and compared with a classic al enzyme kinetic assay, The IRMAs involve two monoclonal antibodies, one that reacts equally well with renin and prorenin and one that reco gnizes renin well but prorenin only minimally, Prorenin reactivity wit h the second antibody was enhanced by adding the renin inhibitor, Remi kiren, to plasma, The complex of prorenin with this active-site ligand undergoes a conformational change, whereby prorenin is converted into a form that cannot be differentiated from renin by the IRMA. The line ar working range of the assay was 4.0-3000 mU/L. The concentration of prorenin was calculated by subtracting the assay result obtained witho ut Remikiren (i.e., renin) from the result obtained with Remikiren (i. e., renin plus prorenin), No more than 2% of prorenin present in plasm a was detected as renin, The interassay CVs for renin quantification w ere 18%, 13%, and 8% at low, medium, and high concentrations, respecti vely, The interassay CV for calculated prorenin was 8% at both low and high concentrations, The IRMA results were highly correlated with tho se of an enzyme kinetic assay in healthy subjects; in patients with su ch conditions as primary hyperaldosteronism, renovascular hypertension , and low-, medium-, and high-renin essential hypertension; and in wom en undergoing gonadotropin stimulation.