Relapsing Steroid-Resistant Primary FSGS Treated with Plasmapheresis

Introduction: Focal Segmental Glomerulosclerosis (FSGS) constitutes 35% of Nephrotic Syndrome (NS) cases in the US, being the primary glomerular disease in End-Stage Kidney Disease (ESKD). Primary FSGS (pFSGS) presents with acute onset of NS, hematuria (50%), and hypertension (20%). Treatment focuses on reducing proteinuria, typically with Immunosuppression. This case report explores the use of plasmapheresis, a less common treatment, in a young man with relapsing steroid resistant (RSR) FSGS and severe NS. Case Description: A 22 year old male with history of RSR pFSGS, and atrial fibrillation, presented with worsening edema. He had been treated with multiple immunosuppressive agents including cyclosporine, cyclophosphamide, rituximab, IvIG and was currently on MMF, Tacrolimus and prednisone. Vital signs were stable. On examination he had 3+ bilateral lower extremity edema. Labs showed proteinuria of >50g/d and creatinine at baseline of 0.6. He was initiated on high dose steroids and 5 sessions of plasmapheresis were given on Days 1,2,3,5,&7. After plasmapheresis, serum albumin decreased from <1.5 to 4.5, urine protein went from >2000 mg/dl to <4 mg/dl. The patient was discharged on a steroid taper with continued MMF/tacrolimus. Discussion: pFSGS is thought to be secondary to a putative circulating permeability factor that causes podocyte dysfunction manifested by widespread foot process effacement. Proposed factors include suPar, CLCF1, microRNA, PAI-1, AT1R, DG, MMPs, POXp3, PARP1, anti-nephrin antibodies, and CD40. In this patient, the circulating factor is hypothesized to be an antibody released by plasma cells. This hypothesis is supported by the patient’s dramatic response to plasmapheresis. This case provides an example of the benefit of plasmapheresis in patients with steroid resistant recurrent nephrotic syndrome due to pFSGS.