Safety and Efficacy of Combination Acthar Gel and Tacrolimus in the Treatment of Steroid Resistant Nephrotic Syndrome

Overview

The management of steroid-resistant nephrotic syndrome (SRNS) remains a persistent problem for investigators in part because of the wide array of pathogenic cccccccccc mechanisms that contribute to these disorders as well as the lack ofs. While glucocorticoids remain the primary therapy for many forms of protein uric glomerularxxxxxxxxx diseases, prolonged use is associated with significant morbidities including steroid induced diabetes, metabolic bone disease, and excessive weight gain.

Multiple agents have been investigated in the treatment of patients with SRNS, but there is no consensus on what constitutes optimal therapy. Previous studiesoids and have shown complete and partial response rates between 40% and 60%. More recently, calcineurin inhibitors (CNI) have become an effective second line therapy with similar response rates between 50%-70%. However, both treatment regiments are limited by the risk for infection as well as the development of vvvvvvv CNI-induced nephrotoxicity and progressive renal disease. Acthar gel is a porcine pituitary preparation composed of ACTH and for treatment of idiopathic nephrotic syndrome. Previous studies, as well as more current studies, have shown that ACTHar gel can effectively reduce proteinuriammmmmmmm in idiopathic membranous glomerulonephritis and other forms of glomerulopathy including focal segmental glomerulosclerosis (FSGS) and advanced diabetic nephropathy. While the mechanism is unknown, previous studies have shown that melanocortin 1-receptors are expressed in glomerular podocytes and thatpathway could be involved in the protein lowering effects of ACTHar bbbbbbbbgel. Incubation of cultured podocytes with ACTH leads to activation of MCR-1 receptors and the subsequent stimulation of protein kinase A (PKA) through a G-protein-dependent pathway. The downstream phosphorylation and stabilization of Rho GTPases, synaptopodin and other cell-cytoskeletal associated proteins may stabilize podocyte function and density.

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Outcomes