Abstract: TH-PO172

Development of Nephrotic Syndrome and Tip-Variant Focal Segmental Glomerulosclerosis during Antiviral Therapy for Hepatitis C Virus Infection

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Rajasekaran, Arun, University of Central Florida College of Medicine, Kissimmee, Florida, United States
  • Casey, Edward T., Orlando VA Medical Center, Orlando, Florida, United States
  • Mendoza, Mario A., Orlando VA Medical Center, Orlando, Florida, United States
Background

Focal segmental glomerulosclerosis (FSGS), associated with focal glomerular damage and podocytopathy, is classically accompanied by proteinuria and high rates of renal progression over time. We describe a patient with Hepatitis C virus (HCV) infection who developed nephrotic syndrome during treatment with direct acting antiviral (DAA) therapies, and a kidney biopsy that demonstrated FSGS-Tip variant.

Methods

A 51-year-old white male with treatment-naïve chronic HCV infection (Genotype-2b) was started on velpatasvir and sofosbuvir. After initiation of DAA therapy, he developed myalgias and lower extremity swelling on day 3, after one month his serum albumin was 1.5 mg/dl (previously 3.9 mg/dl) and at week fourteen a 24-hour-urine collection showed 3469 mg of protein. Evaluation revealed a serum creatinine of 0.8 mg/dl, normal ESR and complement levels. HIV, ANA, ANCA, and cryoglobulins were negative. He was started on lisinopril and atorvastatin. A renal biopsy 5 months after start of DAA treatment showed normal sized glomeruli that exhibited segmental increase in mesangial matrix and cellularity. Half of the glomeruli displayed segmental glomerulosclerosis, with cellular features that projected into the initial segment, and adherent to the origin of the proximal tubule segment, fulfilling criteria for glomerular tip lesions. Immunofluorescence revealed negative staining for IgG, IgM, IgA, C3, C1q, albumin, fibrinogen, and lambda and kappa light chains. Electron microscopy depicted visceral epithelial cells with severe diffuse foot process effacement, with no immune-type electron dense deposits. These findings were consistent with FSGS with glomerular tip lesions. High-dose steroids were initiated, and his proteinuria markedly improved in 3 weeks, with a urine protein-to-creatinine ratio of 0.431. He attained sustained virological response at 12 weeks post DAA therapy.

Conclusion

FSGS is a disease of podocyte injury that leads to proteinuria. We describe a patient with treatment-naïve HCV infection who developed nephrotic syndrome within days after starting DAA therapy and a kidney biopsy 5 months later revealed tip-variant FSGS. His proteinuria markedly improved after high-dose steroid therapy. Physicians should be aware of this newly emerging renal adverse effect associated with DAA therapy.