Human prorenin: pathophysiology and clinical implications.

Renin and prorenin, the latter after conversion to renin, are usually measured by indirect RIA using antibodies against angiotensin I. They can now also be measured by direct RIA using monoclonal antibodies reacting with total immunoreactive renin (renin plus prorenin) or with renin alone. Results of measurements in renal and peripheral venous plasma indicate that normally a large proportion of prorenin in plasma is of renal origin and they support the concept of separate pathways for prorenin and renin secretion by the JG-cells. Acute stimulation causes a prompt increase of plasma renin without any change in prorenin. During chronic stimulation both renin and prorenin are increased, in such a way that the ratio between the two is higher the stronger the stimulus. Thus, with acute stimulation only the release of stored renin appears to be increased (regulated pathway), whereas during chronic stimulation the synthesis and secretion of prorenin are also (constitutive pathway). During pregnancy, in the early luteal phase of the menstrual cycle and after ovarian hyperstimulation with gonadotropins, a normal or somewhat elevated plasma level of renin is associated with a disproportionally high level of prorenin. This is an indication of extrarenal production of prorenin and in these conditions the ovary, probably corpus luteum, seems to be the main source. In most patients with renin-producing tumors plasma prorenin is also disproportionally high. In diabetes mellitus complicated by micro-angiopathy plasma prorenin is also elevated whereas renin is normal or even low. In diabetics with end-stage nephropathy we found no significant veno-arterial difference in prorenin across the kidneys, despite high circulating prorenin and a very low blood flow through these kidneys, suggesting that also in these patients part of the increased prorenin in plasma is of extrarenal origin. Thus, measurements of prorenin in plasma in various pathological conditions may contribute to a better understanding of the physiological role of the renal and extrarenal renin-angiotensin systems.