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Abstract: FR-PO0897

Collapsing FSGS in the Setting of Fabry Disease

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

  • Begum, Farhana, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
  • Canetta, Pietro A., Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
  • Wooden, Benjamin, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
Introduction

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene, leading to deficient or absent α-galactosidase A activity. This results in progressive glycosphingolipid accumulation, particularly in podocytes, tubular epithelial cells, and vascular endothelium. The deposition induces podocyte injury, chronic inflammation, and fibrosis, typically presenting with proteinuria, progressive glomerulosclerosis, and chronic kidney disease.

Case Description

A 63-year-old woman with a history of renal cysts, hypertension, hyperlipidemia, and remote preeclampsia presented with bilateral thigh pain, inability to ambulate, and upper respiratory symptoms following recent use of 5 doses of NSAIDs. Initial labs revealed acute kidney injury (Cr 5.79; baseline 1.3), thrombocytopenia (25K), elevated CK (841), hematuria, and proteinuria (UPCR 1.8 g/g). Infectious work-up showed EPEC on GI PCR, Group B Streptococcus on urine culture, and equivocal Leptospira IgM (PCR negative, treated with doxycycline). Viral studies (HIV, EBV, CMV, parvovirus, COVID-19) and serologic evaluation (complement levels, ANA, ANCA panel) were negative.
Kidney biopsy demonstrated collapsing glomerulopathy, moderate tubular atrophy and interstitial fibrosis, and diffuse tubular cytoplasmic vacuolization. Scattered myelin figures (Zebra bodies) were identified. Immunosuppression was not administered in the hospital in the midst of a possible infection. Peak inpatient creatinine reached 6.73 mg/dL; discharge creatinine was 5.35 mg/dL. Genetic testing revealed a pathogenic variant in the GLA gene, confirming a diagnosis of Fabry disease. The patient has not demonstrated renal recovery from ATN and is undergoing planning for renal replacement therapy.

Discussion

In Fabry disease, FSGS-like lesions represent advanced disease with podocyte loss and irreversible scarring rather than primary glomerulopathy, often indicating a poor prognosis. Misdiagnosis as primary FSGS can occur, particularly in females or atypical cases. To our knowledge, this is the first reported case of collapsing FSGS associated with Fabry disease, which more commonly presents as slowly progressive CKD without hematuria or RPGN. This case highlights the importance of considering Fabry disease in the differential of collapsing FSGS especially when there are suggestive clinical or histological features.

Digital Object Identifier (DOI)