Microarray analysis of the effects of Acthar Gel versus methylprednisolone in a model of focal segmental glomerulosclerosis in female rats

Acthar® Gel (repository corticotropin injection) is an alternative treatment for patients with focal segmental glomerulosclerosis (FSGS) who cannot tolerate or do not adequately respond to glucocorticoids or calcineurin inhibitors. We compared the effects of Acthar versus methylprednisolone (MP) on gene expression in the kidney cortex in a rat model of FSGS induced by puromycin. Female Sprague-Dawley rats (6-8 weeks old) were treated for 8 weeks with Acthar 60 IU/kg (n = 5), MP 2 mg/kg (n = 5), or control (n = 4). On Day 56, animals were sacrificed, and RNA samples of kidney cortex tissue were analyzed using microarrays. Compared with control, Acthar significantly decreased the expression of more genes related to inflammation, immune function, and fibrosis than MP. A subset of these genes exhibited significantly larger fold changes in expression after treatment with Acthar versus MP, including C1qb and C1qc (complement cascade), Ccr2 and Tcrb (immune function), and Mfap4 and Vim (fibrosis). These results suggest that Acthar acts as an immunomodulator with a distinct mechanism of action from that of MP. Their differential alteration of gene expression in the kidney cortex suggests that Acthar may be more effective than MP in reducing inflammation and fibrosis in FSGS, which could slow disease progression.