Collapsing FSGS from Acquired Nephrin Antibody

Introduction: Deficits in nephrin and other podocyte components are known to result in congenital nephrotic and familial FSGS syndromes. Weins et. al. recently described acquired anti-nephrin antibody localizing in glomerular podocytes of patients with minimal change disease. Case Description: A 16 year old male referred for new onset nephrotic syndrome progressive over 2 weeks was found to have serum albumin 1.2 gm/dL, UPCR 3.1, and elevated lipids with BP 160/100 mm Hg. Hepatitis B/C, HIV, SLE screens were negative. Renal biopsy demonstrated focal collapsing lesions with diffuse podocyte effacement. Immunofluorescence showed punctate IgG, kappa and lambda light chain staining in podocytes, but no albumin. Anti-human IgG colocalized with nephrin in the granular staining. ParvoB19 and COVID-19 titers were negative. Creatinine rose from 0.65 to 1.65 and UPCR to 10.3 but improved rapidly with high dose prednisone and ACEi. Serology for circulating anti-nephrin 2 weeks into treatment was negative, consistent with previous finding that circulating antibody levels quickly drop to low or undetectable with partial clinical remission. Discussion: This case strengthens evidence that anti-nephrin antibodies cause disruption of the slit pore diaphragm which appears to be readily responsive to immune therapy. Anti-nephrin mediated podocytopathy may present with a spectrum of glomerular histopathology, which on the background of other susceptibility factors, can lead to more severe presentations such as collapsing FSGS.Yellow represents merge of IgG and anti-nephrinPunctate IgG stain in podocytes