SUN-001 A NEURO-RENAL SYNDROME WITH NEUROFASCIN ANTIBODIES

Abstract

We present a case of focal segmental glomerulosclerosis (FSGS) and acute-onset chronic inflammatory demyelinating polyneuropathy (CIDP) associated with rare neurofascin autoantibodies, supporting a newly defined neuro-renal syndrome. A 48-year-old African-American male presented to the hospital with lower extremity paresthesias that progressed rapidly to bilateral upper and lower extremity weakness with areflexia. He underwent an electrodiagnostic study that demonstrated sural sparing, absent F waves, conduction block and markedly reduced recruitment of normal appearing motor unit potentials, consistent with acute inflammatory demyelinating polyneuropathy (AIDP) and received 2 gm/kg of intravenous immunoglobulin. He also developed new-onset proteinuria with 10 gm on spot urine albumin:creatinine ratio (UACR). Urine microscopy revealed 10-20 RBCs/HPF with few dysmorphic RBCs and a fine granular cast. A limited kidney biopsy with 3 glomeruli without tubulointerstitial damage on light microscopy (LM) and severe podocyte foot process effacement on electron microscopy (EM) was interpreted as minimal change disease (MCD). He was started on 1mg/kg prednisone daily; however, subsequently developed respiratory failure due to neuromuscular weakness requiring mechanical ventilation and was treated with plasmapheresis for 7 sessions. The patient was later extubated and discharged to acute rehabilitation. He was readmitted 2 weeks later for a suspected AIDP relapse with respiratory failure, again prompting intubation and plasmapheresis for 5 sessions. Proteinuria worsened to 24 gm despite continued treatment with prednisone. A repeat kidney biopsy showed 1/12 glomeruli with segmental sclerosis and acute tubular damage on LM, no deposits on immunofluorescence and severe podocyte foot processes effacement on EM, resulting in a new diagnosis of primary FSGS. In light of waxing and waning symptoms and protracted course he was diagnosed with acute-onset CIDP. A detailed work up returned positive for NF antibodies, NF140 and NF155, that have been reported with IVIG-refractory acute-onset CIDP. He was treated with pulse dose IV methylprednisolone and tacrolimus resulting in marked improvement of both proteinuria of 100 mg and polyneuropathy over 6 months of follow up. FSGS and CIDP may share immunopathogenic mechanisms. NF is a protein encoded by NFASC gene and belongs to the L1 family of immunoglobulin cell adhesion molecules that are involved in neuronal growth and development. NF is a paranodal protein, critical to neuronal transmission. Interestingly, NF is also a part of podocyte cytoskeleton. The presence of NF antibodies and concurrence of severe proteinuria and polyneuropathy suggests a strong neuro-renal interface. NF antibodies are typically of the IgG4 subclass. Physicians should have a high clinical suspicion for sampling errors on kidney biopsy if the disease in question does not seem to respond to adequate treatment. Our patient was first diagnosed with MCD and AIDP; however, despite adequate treatment suffered a relapse and was later diagnosed with FSGS and a rare subtype of CIDP. The pathophysiological role NF 140 and NF 155 antibodies in FSGS and their prognostic significance needs validation in further studies.