Renin and prorenin disappearance in humans post-nephrectomy: evidence for binding?

To study the distribution of kidney-derived renin-angiotensin system (RAS) components in humans, we monitored the decline in plasma prorenin, renin, angiotensin (Ang) I and Ang II post-nephrectomy. Prorenin and renin decreased biphasically, prorenin displaying a slower elimination. The distribution half life was similar for both. Angiotensins followed the disappearance of renin. One-two days post-nephrectomy, stable plasma concentrations at 5-10% (renin and angiotensins) and 25-30% (prorenin) of pre-nephrectomy levels were reached. The total amount of kidney-derived renin and prorenin in the body was approximately 10 times as much as the amount in blood. Prorenin also originated at extrarenal sites. The renin levels in anephrics corresponded with the percentage of prorenin that in vitro has a so-called 'open conformation' (i.e., displays enzymatic activity), suggesting that renin in anephrics is in fact 'open' prorenin. Haemodialysis nor captopril significantly affected the level of any RAS component in anephrics. In conclusion, renal renin/prorenin enter tissue sites in humans, and renal renin is the main determinant of plasma angiotensins. Whether prorenin contributes to tissue angiotensin generation in humans remains to be determined.