Abstract: FR-PO836
A Case of Collapsing FSGS: Lupus Podocytopathy or APOL1-Mediated Kidney Disease?
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Mistry, Kavita, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
- Stillman, Isaac Ely, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Lecker, Stewart H., Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
Introduction
High risk APOL1 alleles are a key driver of proteinuric kidney disease in the Black population. Although the combined allele frequency among African Americans is 34%, only a minority of individuals with two APOL1 risk alleles go on to develop kidney disease, suggesting the need for a second hit.
Case Description
A 59-year-old African American woman with a history of undifferentiated connective tissue disease and monoclonal gammopathy of unknown significance (MGUS) presented with 6 weeks of fevers of unknown origin, fatigue and malaise. Vital signs were normal and physical exam revealed axillary lymphadenopathy. Creatinine was 0.7 mg/dL with albumin of 3.0 g/dL and 2.8 g/g proteinuria. SPEP and UPEP revealed monoclonal IgG kappa light chain estimated at 84 mg/day in urine. Bone marrow biopsy revealed 9% plasma cells consistent with MGUS. Infectious diseases workup was negative apart from positive CMV IgM. Nephrology and rheumatology were consulted and recommended workup as follows: ANA positive 1:1280, dsDNA positive 1:1280, C3 slightly low at 84 mg/dL, C4 normal, anti-PLA2R IgG negative, HIV and hepatitis B/C serologies negative, and positive antibodies for RNP, anti-Sm, SS-A and SS-B. The patient was started on prednisone 60 mg/day for presumed lupus nephritis. A renal biopsy was performed and revealed collapsing focal segmental glomerulosclerosis (cFSGS) with negative immunofluorescence. Electron microscopy revealed extensive foot process effacement with no subendothelial deposits and rare subepithelial deposits, consistent with lupus podocytopathy. The patient was discharged on ARB and SGLT2 inhibitor and proteinuria improved to 0.3 g/g. Steroids were tapered off and mycophenolate was initiated. APOL1 genotyping returned as high risk G2/G2. Mycophenolate was tapered off due to gastrointestinal side effects with no rebound increase in proteinuria, suggesting that this patient’s cFSGS was driven by APOL1-mediated kidney disease triggered by CMV infection rather than by lupus podocytopathy.
Discussion
This report adds to a growing literature of cases that describe cFSGS in patients with high risk APOL1 alleles after viral infection. The biological basis for the development of cFSGS in patients with APOL1 high risk genotype, lupus and viral infection remains to be elucidated, although can be presumed to result from parallel, additive and/or synergistic processes.