Neuro-renal syndrome (NRS) in autoimmune nodopathies and paranodopathies: A warning to consider the diagnosis when anti-node and paranode antibody tests are difficult to perform.

INTRODUCTION

Neuro - renal syndrome (NRS), a neuroimmunomediated entity that presents with acute nephrotic syndrome (primarily membranous glomerulonephritis), recurrent proteinuria, and even acute renal failure requiring dialysis, has been reported with varying prevalence in patients with immunomediated neuropathies and paraneoplastic syndromes. Pathophysiologically, IgG 3 and IgG 4 antibodies target the peripheral nervous system (PNS) and central nervous system (CNS), leading to predominantly distal weakness, sensory ataxia, and electrophysiological abnormalities. The patient tends to be refractory to intravenous immunoglobulin due to the pathophysiology of IgG 3 or IgG 4 antibodies but responds favorably to plasmapheresis and anti- CD 20 therapy. Additional investigations revealed a definitive diagnosis through positive antibody levels on tests such as the transfected CBA, using commercial or in- house kits.

OBJECTIVE

To describe the relationship between the clinical presentation of nodopathies and paranodopathies with immunomediated origins and acute nephrotic syndrome, recurrent proteinuria, and acute renal failure requiring dialysis, and to identify factors that alter prognosis and therapeutic options.

METHODOLOGY: Systematic review of NRS. Our postdoctoral project was approved by the local ethics committee (protocol no. 34144620.7.1001.5363.7.1001.5363. 7. 1001. 5363. 7. 1001. 5363) at FMUSP- RP.

RESULTS AND DISCUSSION: NRS has been recently described and partially explained, with neuropathies linked to nodal antigens such as neurofascin (NF) 146 and 188, NF paranodal 155, contactin 1 (CNTN- 1), and the contactin 1 (CASPR- 1) complex, representing warning signs consistent with an expanded phenotype and therapeutic refractoriness. We believe that NRS (and its variants) is a comorbidity that contributes to the pathophysiology of immunomediated conditions, with potentially catastrophic evolution if not recognized early.

CONCLUSION

To describe NRS (with its variants) with early renal involvement and failure of first- line immunotherapies, due to the predominance of IgG 3 or IgG 4 antibodies. Identifying the clinical spectrum of NRS in nodopathies and paranodopathies can directly impact management, including early plasmapheresis and anti- CD 20 therapies, aiming to prevent early axonal loss, irreversible comorbidities, and increased mortality in a subacute- onset chronic neuropathy.