Abstract: TH-PO689
A Child with Exostosin 2-Associated Membranous Nephropathy
Session Information
- Glomerular Diseases: Case Reports - 1
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Vegh, Nicole, Louisiana State University, Baton Rouge, Louisiana, United States
- Yosypiv, Ihor V., Tulane University School of Medicine, New Orleans, Louisiana, United States
Introduction
Unlike adults, membranous nephropathy (MN) comprises only 1-2% of childhood nephrotic syndrome. Primary MN is driven by the formation of immune complexes formed by specific antibodies targeting antigens along the subepithelial region of the glomerular basement membrane (GBM). Exostosin 1 and exostosin 2 (EXT1/EXT2) antigens identify a unique form of MN associated with autoimmune disease, such as lupus.
Case Description
A healthy 9-year-old African American boy presented to emergency department for thoughts of suicidal ideation and self harm due to bullying at school. Vital signs and physical examination were normal. Family history was positive for lupus nephritis requiring kidney transplantation. Labs showed normal eGFR, reduced serum albumin (2.5 g/dL), negative ANA, normal C3/C4 complement levels, negative HIV, hepatitis panel, RPR, TB QuantiFERON gold and TSH. Urinalysis (UA) was negative except increased protein to creatinine ratio (5.061 mg/mg). Nephrology started prednisone (2mg/kg/day) treatment of nephrotic syndrome. Lack of remission triggered renal biopsy which showed diffuse global holes and spikes along the thickened GBM, +4 IgG, trace IgA, 3+ C3, 3+ kappa, +3 lambda, EXT2+, global subepithelial and intramembranous electron dense deposits with severe epithelial foot process effacement. Renasight gene panel was negative. A diagnosis of primary EXT2-positive membranous nephropathy was made. EXT2 encodes glycosyltransferase involved in the chain elongation step of heparan sulfate biosynthesis. Prednisone was stopped and lisinopril was started for nephroprotection. Proteinuria resolved within ~2 months and lisinopril was stopped.
Discussion
This case illustrates that EXT2-positive MN is associated with good short-term clinical outcomes in children. Given that kidney EXT2-positivity is associated with autoimmune diseases, most commonly lupus nephritis, long-term monitoring is required. This case highlights that through identifying specific podocyte antigens, we can tailor individuals’ care. Knowledge of the association of EXT2 with lupus nephritis allows for better anticipatory guidance to families.