Direct Renin Assay and Plasma Renin Activity Assay Compared

The enzyme renin ( M r ∼40 000) is released in an active form from the renal juxtaglomerular cells in response to physiologic factors, including sodium depletion, decreased blood volume and blood pressure, and β-adrenergic stimulation (1). Although several local angiotensin II-generating systems exist within various tissues (including the heart, brain, and adrenal glands), the concentration of active renin in plasma depends on the rate of renin secretion from the kidneys (2). Renin catalyzes the formation of angiotensin I (AngI) by cleavage of the renin substrate called angiotensinogen. Plasma renin is therefore the initiator of the renin-angiotensin-aldosterone system, which has an important role in the homeostasis of water and electrolyte balance and in the regulation of arterial pressure. In most studies, circulating renin has been estimated by assays of plasma renin activity (PRA). PRA is measured by generating AngI from endogenous angiotensinogen, followed by measurement by RIA of the generated AngI. Although PRA measurement is convenient for estimating the biological activity of the renin system, it may not necessarily reflect the real concentration of active renin. The concentration of substrate rarely affects the PRA result, but exceptions do occur (3). More importantly, PRA depends not only on renin, but also on factors that influence the renin–renin substrate interaction. An additional difficulty occurs in measuring low concentrations of renin. In the PRA method, prolonged incubation is needed to generate measurable AngI. This is specifically important when measuring PRA in black people because their values are often below the limit of detection of the routine PRA method. This complicates and prolongs the method and makes it impractical for large throughput for population-based studies. Immunoassays are available to quantify renin directly with use of monoclonal antibodies. In addition, interlaboratory CVs are lower with immunoassays than with PRA assays (4). A new method for …