#3226 A case report of a concurrent axonal neuropathy and focal segmental glomerulosclerosis treated with ocrelizumab and plasma exchange

Abstract Background and Aims There are documented cases of concurrent focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) with inflammatory polyneuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) and Guillain-Barré syndrome (GBS) [1, 2]. However, the pathogenesis linking the two is unclear. Previous cases have been treated with immunosuppression and plasma exchange (PLEX) [1, 2]. Both neurological and renal improvement with immunosuppression and PLEX suggests a common autoimmune pathogenesis. Method We describe a case of a patient with FSGS and an axonal neuropathy, both of which responded to PLEX and immune agents including B-cell depleting therapies. Given multiple previous drug reactions, ocrelizumab, a humanized anti-CD20 monoclonal antibody usually reserved for multiple sclerosis (MS), was used as a novel therapy in this case with reasonable efficacy in our patient when they suffered a relapse. Results A 54-year-old female presented with renal failure requiring dialysis with a creatinine of 616 μmol/L and urine protein:creatinine ratio of 3076 mg/mmol. Biopsy revealed resolving acute tubular injury, MCD, FSGS and thin membrane disease with negative immunofluorescence. She was initially treated with steroids. Repeat biopsy at 3 months was most consistent with MCD and FSGS. Given ongoing dialysis dependence she was treated with PLEX and rituximab with an improvement in renal function to a creatinine of 129 μmol/L but ongoing proteinuria. She was weaned off dialysis but required maintenance PLEX. She was started on tacrolimus but transitioned to ciclosporin due to side effects. A third biopsy was performed showing FSGS. PLEX was eventually weaned after 2 years. She remained off kidney replacement therapy for nearly 3 years. 3 years post her initial presentation, she re-presented with renal failure requiring dialysis and a progressive mixed motor and sensory lower limb neuropathy. Nerve conduction studies were most consistent with GBS and nerve biopsy showed an axonal neuropathy. Repeat renal biopsy showed FSGS with mild interstitial inflammation. Vasculitis screen was negative apart from a positive ENA and anti-SSA. A genetic nephrotic panel was unremarkable. The patient recommenced PLEX and received IVIG and rituximab. Unfortunately, she had a severe reaction to rituximab requiring steroids, however her neuropathy and renal injury improved. She was maintained on PLEX ongoing. She had two further neuropathy flares over the following 18 months, both treated with more intense PLEX regimens. During the second flare she was unable to be weaned from three times a week PLEX. Given previous reactions to tacrolimus, rituximab and IVIG she was trialled on ocrelizumab. Subsequently PLEX was weaned to fortnightly to good effect. The patient's renal function is stable with a creatinine of 200 μmol/L and an albumin:creatinine ratio of 225 mg/mmol. She remains off dialysis. Conclusion The mechanism linking FSGS and inflammatory neuropathies is unclear. However, the response to PLEX and B-cell depleting therapies suggest an autoimmune component with perhaps a common circulating antibody or factor yet to be identified. Further research into a unifying pathophysiology is needed. Additionally, to our knowledge ocrelizumab has not been used for FSGS prior to our case. We found one case report where ocrelizumab was used in membranous nephropathy with concurrent MS [3]. Our case illustrates the potential role for other antiCD20 agents other than rituximab, such as ocrelizumab, for patients with concurrent FSGS/MCD and inflammatory neuropathies.