During the last 15 years 8 patients were diagnosed with renin secreting juxtaglomerular cell tumors among 30,000 hypertensive patients. Clinical characteristics included severe hypertension poorly medically controlled in young patients (mean age 22.3 years) and severe hypokalemia (mean 2.83 mmol./l.). Secondary hyperaldosteronism was present in all cases with a constant elevation of renin activity. Renal vein sampling was only positive in 64% of cases. Selective renal arteriography demonstrated an avascular area in 43% of the patients. Computerized tomography showed the tumor in all cases. Mean tumor size was 24 mm. (range 10 to 50). Conservative surgery was feasible in all patients. Perioperative ultrasonography was used for 3 intraparenchymal tumors. Hypertension and hypokalemia resolved within 1 week after surgery. At a mean followup of 98 months (range 24 to 204) no tumor recurrence was documented.

A bstract. Monoclonal antibodies directed against human renin were obtained by the fusing of myeloma cells with spleen cells from Balb/c or highresponder Biozzi mice injected with pure tumoral or highly purified renal renin. These procedures resulted in the production of seven stable monoclonal antibodies to human renin. Antibodies in the hybridoma culture medium were screened by binding to pure iodinated renin or insolubilized renin in a solid phase assay. The concentration of purified antibodies that provided a 50% binding to iodinated renin varied from 1 X 10-10 to 1 X 10-7 M. Two monoclonal antibodies were found to be potent inhibitors of renin enzymatic activity in vitro, behaving as noncompetitive inhibitors (Ki, 1 to 4 X 10`s M). They were specific for primate renin. Three monoclonal antibodies provided suitable immunoadsorbants for renin purification. One of these immunoadsorbants was used for large-scale purification of the renal enzyme, resulting in an 825-fold renin enrichment in a single step. Two antibodies were able to distinguish between active and inactive renin and enabled concomitant separation and purification of the two enzyme forms in various biological fluids. Monoclonal antibodies also stained human and monkey renal renin when indirect immunofluorescence and peroxidase-antiperoxidase techniques were used. A highly sensitive radioimDr. Atlas is with the

Antibodies were raised in rabbit against pure human renin. The antisera obtained are highly specific for human renin versus hog, dog and rat renin. They do not cross-react with acid proteases such as pepsin and human cathepsin D. A direct radioimunoassay is described for human renin in plasma and kidney extracts. 30 to 50 pg of enzyme (2.5 to 4 x 10(-5) Goldblatt units) are detected.

During the past 10 years, we have found renin-secreting renal juxtaglomerular cell tumors in three hypertensive patients (two women, one man, aged 22, 69, and 21 years, respectively). The major chemical and biological findings revealed the association of severe hypertension with hypokalemia and increased plasma renin activity and plasma aldosterone. The diagnosis of such tumors is difficult, and two of the three patients were followed up for four and five years respectively before undergoing surgery. The pharmacological blockade of the renin system by various agents (beta-blockers, angiotensin II antagonists, and captopril) and its effects on blood pressure and plasma renin activity proved to be unreliable. Renal venous catheterization for renin measurements failed to provide adequate localization of the tumor. Direct radioimmunoassay, however, showed the total plasma renin to be markedly elevated. In addition, renal arteriography showed an avascular area corresponding to the renin-secreting tumor in each of the three patients. All three patients were cured of hypertension and hypokalemia by excision of the tumor.

1 CGP 38 560 A, a low-molecular-weight, non-peptidic renin inhibitor, was well tolerated upon intravenous and oral administration to recumbent healthy volunteers on an unrestricted-sodium diet. 2 After intravenous infusion over 30 min at a rate of 100 ml h-, doses of 50, 125 and 250 ,ug kg-' appear to induce a long-lasting inhibition of plasma renin activity. Plasma angiotensin II was decreased in a dose-dependent manner during the infusion and thereafter reverted to the initial level. A concomitant dose-related increase in active plasma renin was observed. Blood pressure was unaffected. The plasma levels of CGP 38 560 reached during infusion were at least 2000-fold higher than the theoretical inhibitory concentration based on in vitro results. 3 After oral administration in doses of 50, 100 and 200 mg CGP 38 560 A, inhibition of plasma renin activity was observed, but plasma active renin was unchanged. Blood pressure also remained unaffected. 4 CGP 38 560 was rapidly cleared from plasma with a half-life of 7.6 min for the first phase and 63 min for the second phase. Plasma levels were 100-fold lower after oral administration than after infusion, indicating a low degree of absorption (< 1% oral bioavailability).Keywords angiotensin II plasma renin activity active renin renin inhibitor