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Kidney Week

Abstract: SA-PO1016

A Case of Steroid-Resistant Focal Segmental Glomerulosclerosis in a Patient with a Heterozygous Mutation of COL4A3 Gene Variant of Uncertain Significance

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Rudy, Mark, University of Kentucky College of Medicine, Lexington, Kentucky, United States
  • Donaldson, Katherine, University of Kentucky College of Medicine, Lexington, Kentucky, United States
  • Biederman, Laura, The Ohio State University, Columbus, Ohio, United States
  • Ahmed, Sadiq, University of Kentucky College of Medicine, Lexington, Kentucky, United States
Introduction

Focal segmental glomerulosclerosis (FSGS) is a histopathological lesion that can manifest as severe hypertension, proteinuria, and nephrotic syndrome. FSGS can be a primary disorder or a secondary process related to medications, viruses, or genetic mutations. In this case, a 21-year-old patient presents with nephrotic syndrome secondary to collapsing FSGS with a heterozygous mutation of the COL4A3 gene.

Case Description

A 21-year-old black male presented with nephrotic syndrome. Labs revealed urine protein to creatinine ratio (UPCR) of 6.9 g/g, hematuria with 21-50 RBC/hpf, serum albumin of 1.1 g/dL, and serum creatinine of 1.2 mg/dL. A kidney biopsy showed minimal change disease. He was treated with high dose prednisone and tacrolimus. At 8 weeks, the patient had a UPCR of 14.5 g/g, serum albumin of 0.8 g/dL, and serum creatinine of 7.1 mg/dL. A second kidney biopsy was performed, showing collapsing FSGS with normal thickness of the glomerular basement membrane (Figure 1). Infectious work-up for HIV, hepatitis A, B, and C was negative. A Renasight kidney genetic panel revealed a heterozygous mutation (p.Leu648Ile) of the COL4A3 gene with autosomal dominant and autosomal recessive inheritance patterns. It is a variant of uncertain significance, absent from the Broad gnomAD dataset. Patient was started on hemodialysis after failing immunosuppressive management.

Discussion

Heterozygous mutations of COL4A3 in patients with treatment-resistant FSGS with a normal glomerular basement membrane have been reported in the literature. Recognizing new genetic variants will help with developing future therapies and avoiding ineffective immunosuppression. More research will be necessary in this field.