Sample Requirements for Plasma Renin Activity and Immunoreactive Renin

Renin, an aspartic protease, is rate limiting in the generation of angiotensin (Ang) II, which is a key regulator in the maintenance of salt and water balance by regulating aldosterone secretion and blood pressure (1). Renin is synthesized and secreted into the blood exclusively by the juxtaglomerular cells of the kidney from prorenin, an inactive precursor, which is produced not only by the kidney, but by other tissues, including the adrenal glands, gonads, and the uteroplacental unit (2). Whereas the secretion of renin is tightly controlled, prorenin secretion is not and is ∼10-fold higher than renin (3). Although peripheral conversion of prorenin to renin is limited and does not typically occur in vivo, in vitro conversion of prorenin to renin can occur by cryoactivation, so sample handling is critical (4). Historically, samples for renin activity have been collected on ice, frozen, and assayed at 2–8 °C. Cryoactivation occurs when samples are exposed to refrigerated temperatures (4 °C) for extended periods of time (4)(5)(6)(7)(8). Because of the high concentration of prorenin relative to renin, cryoactivation can lead to a marked increase in renin concentration. Therefore, to avoid cryoactivation, samples should be collected and assayed at room temperature. Recently, IRMA assays have been developed to directly measure renin in the circulation.