An inactive, prorenin-like substance in human kidney and plasma.

1. Plasma prorenin (inactive renin), which accounts for about 70% of the total renin in human plasma, was almost completely separated from active renin by affinity chromatography on Cibacron blue F3G-A-agarose. The slight residual renin activity present in the prorenin peak can be removed on concanavalin A-Sepharose, demonstrating that prorenin is completely inactive. 2. The renin activity of both human renal cortical extract and renal perfusate increased after incubation with trypsin. This trypsin-activable renin accounted for 15 and 40% of the total renin in extract and perfusate respectively. 3. Trypsin-activable renin from both renal extract and renal perfusate was, like plasma prorenin, almost completely separated from active renin on Cibacron blue F3G-A-agarose. After additional chromatographic steps, the trypsin-activable renin from renal cortical extract was found to be completely inactive. 4. We conclude that human kidney contains, and is able to release, a trypsin-activable renin that resembles plasma prorenin. It may differ from many of the 60 000 molecular-weight forms of renin previously identified in renal extracts, since these possess considerable intrinsic renin activity and probably represent a complex of renin with a binding protein.