Characterization studies of inactive renin from human kidney and from several plasma sources

Plasma of normal pregnant women and plasma of some patients with diabetic nephropathy contain increased quantities of an inactive form of renin compared with normal plasma. In order to evaluate the significance of the increased levels of inactive renin in these conditions, we isolated and compared inactive renin from several plasma sources and from human kidney. Renal inactive renin and inactive renin from normal plasma and plasma of patients with diabetic nephropathy and plasma of pregnant women displayed reversible acid activation and similar binding characteristics to cibacron-blue. Using cibacron-blue affinity chromatography, we obtained a totally inactive renin preparation from renal cortex and from plasma of subjects from each of the clinical states. Gel filtration of these preparations and detection of inactive renin using a modified acid activation technique indicated that human inactive renin exists in at least two forms with the following apparent molecular weights: 56,300 +/- 1,500 and 49,200 +/- 1,000 for renal inactive renin, 58,000 and 49,000 for inactive renin in normal plasma, 58,500 and 52,000 for inactive renin in diabetic plasma, 57,000 and 49,000 for inactive renin in pregnancy plasma. These studies suggest that: 1) the kidney is a major source of circulating inactive renin in man, 2) inactive renin from normal, diabetic and pregnancy plasma is similar, and 3) human inactive renin is heterogeneous.