Characterization and Source of a Renin-like Enzyme in Anephric Humans1

Plasma renin activity was studied in 6 anephric subjects, 5 women and 1 man, for periods varying from 1 to 8 months post nephrectomy. In 4 of the 6 subjects, all women, considerable quantities of a renin-like enzyme were found. In 2 patients, increasing concentrations of plasma “renin” occurred with lengthening of the post-nephrectomy period. Biochemical properties including chromatographic characteristics, the velocity curve for angiotensin formation and Michaelis-Menten Constants, indicate that the extrarenal renin was indistinguishable from human renal renin. Properties of the anephric plasma renin differed substantially from the enzymes kallikrein and pepsin, both of which are capable of releasing vasoactive peptides from plasma. Isolated vasoactive peptides formed from the anephric plasma renin were identified as angiotensin I. Tissues were obtained from one long-term anephric patient (8 months) at autopsy. Extraction and assay of adrenal gland, heart, ileum, liver, lung, ovary, submaxillary gland, stomach, thyroid, and uterine tissues demonstrated renin-like activity only in uterine tissue. These findings indicate, for the first time in man, the possibility of an extrarenal site of renin synthesis, with uterus as one likely source. The possibility of an extrarenal source of renin in the male could not be either confirmed or excluded in this study since the one male had been anephric for a period of only 1 month. Clinical implications of these observations in relation to pregnancy and the syndrome of toxemia of pregnancy are discussed.