Abstract: TH-PO151
Membranous Nephropathy Associated with Immune Checkpoint Inhibitors: A Report of Two Cases
Session Information
- Drug Events Trainee Case Reports
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1500 Onco-Nephrology
Authors
- Meraz-Munoz, Alejandro Y., University Health Network, Toronto, Ontario, Canada
- Chan, Christopher T., University Health Network, Toronto, Ontario, Canada
- Avila-Casado, Carmen, University Health Network, University of Toronto, Toronto, Ontario, Canada
- Kitchlu, Abhijat, University Health Network, Toronto, Ontario, Canada
Introduction
Immune checkpoint inhibitors (ICI) are novel cancer immunotherapies with recognized nephrotoxicities. The most common toxicity is acute tubulointerstitial nephritis, but cases of glomerular injury have been reported. We describe 2 patients with membranous nephropathy (MN) associated with pembrolizumab.
Case Description
Case 1: 52-year-old woman with stage III ovarian cancer, treated with pembrolizumab. She presented with frothy urine and edema. Urine sediment was bland. Investigations demonstrated albumin 3 g/dL, proteinuria 12 g/d and serum creatinine (sCr) 0.7 mg/dL. A biopsy showed thickened glomerular capillary walls. Immunofluorescence showed staining for IgG3(+), Anti-Phospholipase-A2-Receptor antibody [PLA2R](-) and Thrombospondin Type-1 Domain Containing 7A antibody [THSD7A](+). Electron microscopy (EM) showed subepithelial immune-type electron-dense deposits with diffuse effacement of the podocyte foot processes consistent with MN. Pembrolizumab was held and she received prednisone 1 mg/kg with remission of proteinuria. She was re-challenged with pembrolizumab with recurrence of proteinuria. Pembrolizumab was stopped and she received prednisone with resolution of proteinuria.
Case 2: 39-year-old man with stage IV colon cancer, treated with pembrolizumab. He presented with proteinuria 2.2 g/d, sCr 1.1 mg/dL, albumin 3.3 g/dL and bland urine sediment. Biopsy revealed staining for IgG3(+2), Anti-PLA2R(-) and anti-THSD7A(+). EM showed subepithelial immune-type electron-dense deposits with diffuse podocyte effacement. The findings were consistent with MN. He received prednisone and pembrolizumab was held with resolution of proteinuria (0.3 g/d).
Discussion
These are the first reported cases describing the association of MN and pembrolizumab. Although MN is well-described in solid tumors, the timing of onset and remission of proteinuria in these cases is suggestive of immunotherapy-related glomerular injury. Clinicians should be aware of the risk of this nephrotoxicity. Additional studies may elucidate patient and malignancy-related risk factors
Case 1