Fibrillary Glomerulonephritis in a Patient on Dual Immune Checkpoint Inhibitor and Tyrosine Kinase Inhibitor Therapy

Introduction: Fibrillary glomerulonephritis (FGN) is a glomerular disease characterized by nonbranching, randomly arranged 20 nm fibrils which usually stain positive for DNAJB9. The pathogenesis of FGN remains unclear, but recent studies reported an association with autoimmune diseases and hepatitis C infection. Here, we report 2 cases of FGN occurring after dual treatment with an immune checkpoint inhibitor (ICI) and a tyrosine kinase inhibitor (TKI). Case Description: Patient #1 is a 69-year-old man with a history of metastatic thyroid cancer treated with cabozantinib for nine months. This was stopped due to diarrhea, and he was switched to nivolumab/ipilimumab. After the first cycle, the patient developed AKI, with serum creatinine (sCr) 1.9 mg/dL from a baseline of 1.1 mg/dL and UPCR 2g/g Cr. A kidney biopsy was performed and showed FGN along with chronic TMA. Further ICI was held, and rituximab was started. sCr decreased to 1.2 mg/dL, with UPCR 0.18 g/g Cr after two doses of rituximab. Patient #2 is a 77-year-old man with a history of untreated hepatitis C viral (HCV) infection and hepatocellular carcinoma treated with atezolizumab and bevacizumab. After two years of treatment, the patient developed AKI, with sCr 1.6 mg/dL from a baseline of 1.3 mg/dL and UPCR 4.2g/g Cr. A kidney biopsy was performed and revealed FGN. Bevacizumab was held due to significant proteinuria and Glecaprevir/pibrentasvir was started for HCV. Follow-up sCr fluctuated between 1.2-1.4 mg/dL, with 24h urine protein 1.4 g. Discussion: These cases highlight 2 patients treated with dual immunotherapy and targeted therapy who presented with FGN. In the second case, the patient had HCV, which could be implicated; however, glomerular diseases have been described with both ICIs and TKIs. This potential association with FGN warrants further study, particularly given FGN’s poor prognosis and the implications it has for holding potentially life-saving cancer treatments.