Abstract: PO1676
Anti-Nephrin Autoimmunity in Early Primary FSGS
Session Information
- Podocyte Injury in Human Disease: Pathomechanism, Diagnosis, and Therapy
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1204 Podocyte Biology
Authors
- Weins, Astrid, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Mutter, Walter P., Newton Wellesley Hospital, Newton, Massachusetts, United States
- Keller, Keith H., Brigham and Women's Hospital, Boston, Massachusetts, United States
- Shah, Sujal I., Brigham and Women's Hospital, Boston, Massachusetts, United States
- Rennke, Helmut G., Brigham and Women's Hospital, Boston, Massachusetts, United States
Introduction
Minimal change disease (MCD) and primary FSGS are important diagnoses in adults and children with acute nephrotic syndrome (NS). We have reported anti-nephrin-mediated autoimmunity in NS with MCD on kidney biopsy (KBx). Here, we describe a patient with KBx-proven diagnosis of early primary FSGS and persistent anti-nephrin IgG in glomeruli and serum.
Case Description
A 69yo Caucasian man with history of type 2 DM presents with acute kidney injury (sCr 3.49g/dl), anasarca, hyperlipidemia, sAlb1.8g/dl, UPCR 18g/gCr. Serologies including ANA, HIV, anti-PLA2r are negative; FLC ratio is 2.91. A kidney biopsy is ordered; the differential diagnosis includes MCD, membranous nephropathy, FSGS and paraprotein-related diseases.
The biopsy contains 52 glomeruli with 12% global sclerosis, and 2 glomeruli with early segmental sclerosis with capillary collapse, epithelial hyperplasia and protein reabsorption granules (PRGs). Diabetic glomerular changes are not seen. Tubular atrophy and interstitial fibrosis are mild, and vascular sclerosis is moderate to severe. Immunofluorescence microscopy (IF) shows trace mesangial IgM and fine granular podocyte IgG with equal kappa/lambda. Electron microscopy reveals diffuse podocyte foot process effacement without deposits and loss of slit diaphragms. Confocal imaging of IgG/nephrin IF confirms substantial overlap in the fine podocyte granules (arrows), but not in coarse PRGs (asterisks). A diagnosis of early primary FSGS is made. Sera collected on post-biopsy days 19, 25 and 27 are serologically positive for anti-nephrin.
The patient was started on oral glucocorticoids, and on d27 was in partial remission (UPCR 2.6g/gCr, SAlb 2.8g/dl). Anti-B cell therapy is considered.
Discussion
Our findings reveal that autoimmune-mediated anti-nephrin podocytopathy can trigger irreversible podocyte injury leading to FSGS, likely in patients with additional predisposing factors. This enhances our understanding of diffuse progressive podocytopathies; accurate and early diagnosis identifies patients who benefit most from B-cell-targeted immunosuppressive therapy.