I. Clinical Results and Effects on Proteinuria in One Hundred Six Instances

Abstract

Intially corticotropin (ACTH) and cortisone were used only to induce diuresis in children with the nephrotic syndrome, though occasional remissions were produced.1-7 Most of these early trials were of short duration and the amounts of drugs administered were small because of limited supplies and the occurrence of side-effects such as edema, hypertension, and hypokalemia. The demonstration that such changes could be prevented or minimized by means of diets rigidly restricted in sodium and high in potassium 8 enabled us and others 9,10 to undertake more prolonged administration of large amounts of corticotropin and adrenocortical steroids in the hope of influencing the course of the underlying disease. Materials and MethodsDuring the past five years we have treated a total of 106 instances of nephrotic syndrome in children. All had persistent and usually massive proteinuria on admission. Each patient was treated in essentially the same way, and no attempt was made to exclude those with hypertension, formed elements in the urine, or azotemia. Data on 30 of these children have been reported earlier.8 Seventytwo were initial attacks ; the remainder represented exacerbations. From the information in Tables 1A and IB it can be calculated that the mean age at which the initial episode of nephrotic syn¬ drome occurred in the group of 72 children was 4 years 4 months, with \y2 to 2y2 years the com¬ monest age of onset and a range of 4 months to 13 years 7 months in the remainder. There were more boys than girls, 45 versus 27, and the latter were somewhat older at the first manifestation (4 years 9 months versus 4 years 2 months). Symptoms or signs of nephrotic syndrome, or both, had been present for one week to four years prior to hospitalization for the first course of corticotropin, with a mean duration of 27 weeks. This interval was much shorter, averaging four weeks, in patients who developed an exacerbation while under observation in the dispensary. A his¬ tory of an infection prior to or coincident with the first episode of nephrotic syndrome was obtained in 40 of the 72 patients, with upper respiratory in¬ fection in 34, unexplained fever in 3, varicella in 2, and rubeola in 1 (Table 1A). In the 18 patients admitted one to six times with a total of 34 exac¬ erbations, recrudescence followed an upper re¬ spiratory infection in 12 instances, bronchitis in 1 and was unassociated with any recognized infec¬ tion in the remaining 21 (Table IB). Beta-hemo¬ lytic streptococci were isolated from nose and throat cultures in only a minority of the initial and the subsequent attacks, 12% and 6%, respec¬ tively.

Adrenocorticotropic hormone therapy for the treatment of idiopathic nephrotic syndrome in children and young adults: a systematic review of early clinical studies with contemporary relevance

“…Five studies with 89 patients reported sustained proteinuria response with long-term treatment. The patients were predominantly pediatric (88 %; 341/388 with ages given) with age ≤20 years [ 10 , 13 , 14 , 17 , 31 – 40 ]. Report of proteinuria response was semi-quantitative, including marked reduction, absence or trace level, within normal limits and 1+ level.…”

“…Long-term ACTH treatment results are summarized in Table 2 [ 13 , 17 , 38 – 40 ]. All regimens included an initial short-term daily ACTH treatment course.…”

“…Sustained proteinuria response was examined in the five long-term studies. Evaluation of proteinuria response during long-term ACTH or combined long-term ACTH and post-treatment follow-up showed proteinuria response in 71 % (63/89) of patients [ 13 , 17 , 38 , 40 ]. The two studies that reported proteinuria response post-treatment showed 61 % (19/31) of patients had sustained proteinuria response for up to 26 months [ 39 , 40 ].…”

“…The introduction of ACTH (purified from a pituitary extract) dramatically altered NS management, initially most visibly by providing relief from gross edema through diuresis and then with longer treatment courses enabling sustained proteinuria remission [ 14 , 17 ]. Prolonged, intensive ACTH or steroid therapy improved survival compared to historical control patients; the mortality rate declined to approximately 20–23 % [ 11 , 12 , 18 ].…”

“…The initial ACTH investigations across a broad range of diseases, including NS, are described in the Proceedings of the First Clinical ACTH Conference, held in 1949 in Chicago [ 19 , 20 ]. Studies examining ACTH therapy for NS were published throughout the 1950s, including case studies and large patient cohorts [ 10 , 13 – 17 , 21 – 40 ]. ACTH was largely replaced with the synthetic oral steroid prednisone in the 1960s due to its greater ease of administration and more reliable availability [ 10 ].…”