Conrad M. Riley

Nephrosis of childhood: Statistical evaluation of the effect of adrenocortical-active therapy

Abstract In summary, the evidence now available supports the belief that prolonged and intensive use of adrenocortical-active hormone therapy in childhood nephrosis not only improves the clinical status but also extends life. Only time will tell whether it will prove curative. We have suggested the use of the sedimentation rate as an added simple criterion to help decide when to give or withdraw such treatment.

TREATMENT OF NEPHROSIS WITH ANTI-INFLAMMATORY STEROIDS

Anyone who has had a special interest in nephrosis for 10 years or more will find it easy to call to mind the clinical picture of this affliction in the presteroid days and to contrast it with what we see now. In preparation for this presentation, as I reviewed some of the many reports of the past 8 to 9 years, I discovered that the transition was not as easy or as abrupt as unaided memory would suggest. I t is also interesting to see that, with the use of these new, primarily therapeutic tools and with new developments in allied fields, the concept of nephrosis as a distinct disease entity has grown a little firmer. Therefore, recapitulating the somewhat devious route we have been following seems a worthwhile endeavor. Although 1948 was the year in which the artificial induction of the hyperadrenocortical state was first shown to be capable of altering some types of human disease, it was only at the end of that year that Edith Farnsworth of Chicago, Ill.? requested a supply of corticotropin for use in nephrosis. Early in 1949 she began clinical trials in this and other renal disease, so that she was able to report some effect a t the first ACTH conference in October of that year? Even before her report, others of US had begun to try it in a few cases. When one considers, in the light of present practice, the duration of treatment and the size of the doses given in some of the early trials, it seems a stroke of good fortune that results were sufficiently impressive to justify further exploration of this form of therapy. In May of 1950 at the spring scientific meetings, reports (later published) were submitted by Luetscher? Barnett: and myself6 showing the clinical and metabolic effects of both cortisone and corticotropin on patients with the nephrotic syndrome. By this time it was established beyond doubt that such treatment with adrenocortical-active hormones was quite regularly associated with remission; there was some evidence of improvement in renal function, but much doubt was expressed as to whether the basic disease process was altered significantly. I t is of historic interest that at that time, before aldosterone had been identified, Luetschel3 was able to show by bioassay an excess of “sodium-retaining corticoids” (which disappeared with diuresis) in the urine of nephrotic patients. Review of my own balance data on a patient with induced diuresis shows that the Na:K ratio increases with diuresis, indicating diminished aldosterone activity, an interpretation not appreciated a t the time. Thus there was both direct and indirect evidence for the role, probably secondary, played by aldosterone in nephrosis. Such information justified these drugs as an investigative tool, since they made diuresis an almost predictable possibility. In these early days the methods of giving adrenocortical-active medication showed far more fear of harmful effects than conviction that a valuable new group of therapeutic agents had been discovered. In this brief backward