Beneficial effects of ACTH on the serum lipoprotein profile and glomerularfunction in patients with membranous nephropathy

Background. Previous studies have shown that short-term treatment with adre nocorticotrophic hormone (ACTH) has a strong and rapid lipid-lowering effec t. In this long-term study of nephrotic patients with idiopathic membranous nephropathy, the influence of ACTH on the serum lipoprotein profile and gl omerular function as well as the dose-effect relationship was investigated. Methods. Fourteen patients received ACTH intramuscularly at increasing dose s during 56 days. Serum concentrations of lipids, lipoproteins, and apolipo proteins as well as variables of glomerular function were analyzed, and the side-effects were recorded. ACTH treatment, in the estimated optimal dosag e, was then continued in five patients with severe steroid-resistant nephro tic syndrome. In these five patients, the total treatment period was 12 mon ths, and the follow-up time after discontinuing treatment was 18 months. Results. Taking both the statistically significant therapeutic effects and the modest side-effects into consideration, the optimal dosage of ACTH was estimated to be 1 mg twice per week. At that dose, reductions by 30 to 60% in the serum concentrations of cholesterol, triglycerides, apolipoprotein B , and lipoprotein(a) were observed, whereas the serum concentrations of hig h-density lipoprotein cholesterol and apolipoprotein AI rose by 30 to 40%. In addition, the urinary albumin excretion decreased by 90%, and the glomer ular filtration rate increased by 25%. Deterioration was observed in all ca ses when ACTH was discontinued after a treatment duration of 56 days. Howev er, the five patients in whom ACTH therapy was resumed were still in remiss ion 18 months after discontinuance of treatment. Conclusions. In nephrotic patients with idiopathic membranous nephropathy, treatment with ACTH 1 mg twice per week was associated with significant lon g-term improvements in serum lipoprotein pattern and glomerular function.