Combined Therapy of Cyclosporine A, Mycophenolate, Losartan, and Finerenone in Drug-Resistant NOS-Focal Segmental Glomerulosclerosis

Abstract

Background: Focal and segmental glomerulosclerosis (FSGS) is a common and progressive podopathic glomerulopathy that is resistant to treatment with corticosteroids (70%) and calcineurin-inhibitors (50%). Hence, its primary phenotype is associated with kidney loss in 50% of those with persistent nephrotic syndrome (NS) within 3 - 8 years of diagnosis. The Case: A 26-year-old woman presented with severe NS, hypertension, and hematuria. Investigations excluded genetic mutations, chronic drug use, kidney maladaptations, autoimmune disorders, chronic infections, and toxin exposure. Her kidney biopsy showed focal and segmental glomerular sclerosis with synechial adhesion without cellular proliferation and necrosis, or basement membrane thickening and collapse. On electron microscopy, it showed diffuse effacement of podocyte foot processes. Hence, she had non-otherwise specific FSGS. Her hypertension was controlled with losartan, yet her severe NS (proteinuria > 9 g/day and hypoalbuminemia < 16 g/L) persisted despite sequential 3 months of corticosteroids 60 mg daily, followed by another 3 months of cyclosporine A (CsA) at 100 mg twice daily. However, she responded after the addition of mycophenolate mofetil (MMF) to CsA. Since she was resistant to CsA before, a trial to discontinue it 6 months later was followed by relapse of NS. Hence, CsA was reinstituted, and she responded to it again. At that time, rituximab could not be used due to infusional allergic reactions. After 1 year, the dose of CsA was reduced to 50 mg twice daily to avoid long-term CsA-interstitial fibrosis. Moreover, she remained on losartan and finerenone to decrease glomerular hyperfiltration. By 2 years of follow-up, she remained well with minimal proteinuria (400 mg/day) and normal creatinine clearance (1.8 ml/second). Conclusion: In primary FSGS, multiple mediators may be acting simultaneously and require combined immunosuppressants.