CORTICOSTEROIDS AND ANTIDIURETIC SUBSTANCE IN NEPHROTIC CHILDREN

The role of tubular reabsorption in the pathogenesis of nephrotic edema led the authors to study the participation of antidiuretic hormone and adrenal steroids in regard to changes in renal hemodynamics and tubular function during different clinical events that may induce an increase or a decrease of urinary flow in nephrotic children. Formaldehydogenic steroids in urine, plasma and ascitic fluid and serum antidiuretic substance were simultaneously studied with clearance tests, electrolyte excretion and plasma constituents through 10 different periods of observations. From previous and present studies on renal function it was found that changes in renal hemodynamics and tubular transport mechanisms are responsible for variations in urinary flow leading to accumulation or disappearance of edema in the nephrotic syndrome. An increase in urinary flow was seen to occur with no change in the GFR but with a marked decrease in the U/P inulin and potassium ratio. Serum antidiuretic substance appeared to correlate closely with antidiuresis. Injection of nephrotic sera into peritoneal cavity of rats was followed by an antidiuretic effect similar to that produced by pitressin and posterior pituitary hormone. Antidiuretic factor seemed to be present in the globulin fraction of plasma proteins. No such effect was seen with intraperitoneal injections of plasma albumin, protein-free filtrate and ascitic fluid. An increase in titer of antidiuretic substance was observed during initial doses of ACTH and the reverse at the onset of diuretic response. Urinary excretion of formaldehydogenic steroids depended partly on diuresis in nephrotic children; this was not so in control cases. The influence of tubular function was suggested by the relationship found between urinary excretion of steroids and the V/Cin and V/Cth ratio and between clearance of steroids and diuresis. The influence of renal functional disturbance prevented a correct evaluation of adrenal activity by estimation of urinary steroids in nephrotic children. During the edematous-oliguric stage of nephrosis and in the absence of any stimulating or depressing effect upon the elaboration of adrenal steroids their urinary excretion was not significantly different from that seen in control cases. Formaldehydogenic steroids did not seem to have a direct role in producing variations of urine flow in nephrotic children. Increase and decrease in diuresis occurred simultaneously with an increase and a decrease in urinary and plasma steroids and vice versa. Formaldehydogenic material was found in variable amounts in the ascitic fluid suggesting an appreciable retention in the increased extracellular fluid during the oliguricedematous stage of the nephrotic syndrome. This material appears to be mostly true adrenal steroids. Potassium excretion was related to urinary steroids in nephrotic children but not in control cases. Potassium clearance was related to glomerular filtration in both control and nephrotic children. At the present time it remains a matter of some speculation of the role that steroids present in extracellular fluids may play in the physiologic and morphologic changes known to occur in the course of the nephrotic syndrome and experimentally reproduced by injection of DOCA to animals.