Abstract: TH-PO155
Renal Limited Anti-GBM Glomerulonephritis with Negative Serology in a Patient Following Immunotherapy with Checkpoint Inhibitors
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
- Kyriazis, Periklis Panos, Baystate Medical Center, Springfield, Massachusetts, United States
- Tiwary, Abhinav K., Baystate Medical Center, Springfield, Massachusetts, United States
- Landry, Daniel L., Baystate Medical Center, Springfield, Massachusetts, United States
- Braden, Gregory Lee, Baystate Medical Center, Springfield, Massachusetts, United States
Group or Team Name
- UMMS-Baystate
Introduction
A growing body of evidence implicates checkpoint inhibitor (CPI) immunotherapy as a cause of AKI. Two individual cases of CPI-induced anti-GBM glomerulonephritis (GN) have been reported.We now report the first case of diffuse linear IgG 3+, IgA 2+, Kappa 2+, lambda 1+ anti-GBM GN with negative serology in a patient following CPI exposure.
Case Description
A 58-year-old male undergoing immunotherapy for metastatic melanoma presented with AKI and proteinuria. He had been started on ipilimumab & nivolumab almost a year prior to presentation which was complicated by dermatitis, colitis & hepatitis leading to discontinuation of therapy 3 months later. Due to persistent bilateral lung metastases he was initiated on dabrafenib & trametinib for the next 6 months until he developed AKI with proteinuria. Serologic testing was negative for ANCA, PR-3, MPO, and anti-GBM antibody. Complement levels were normal. Renal biopsy showed focal crescentic (2 of 15 glomeruli with cellular crescents), proliferative and sclerosing GN with diffuse linear staining of glomerular capillary loops dominant for IgG (3+), IgA (2+), Kappa (2+) and lambda (1+). Repeat anti-GBM testing remained negative & the patient's creatinine eventually rose to a peak of 3.8 mg/dL. He had no signs of lung hemorrhage. Dabrafenib & trametinib were discontinued and he was initiated on oral cyclophosphamide (2 mg/kg/day) and pulse intravenous methylprednisolone (1000 mg daily for 3 consecutive days) followed by 1 mg/kg/day of prednisone. Immunosuppression with cyclophosphamide was discontinued after four months of therapy & he was weaned off of prednisone by 6 months. His renal function remained stable for the ensuing 12 months but it started to slowly decline & eventualy he was started on HD.
Discussion
This is a case of anti- GBM GN with negative serology & linear IgG 3+, IgA 2+, Kappa 2+, lambda 1+ anti-GBM likely secondary to treatment with CPI immunotherapy which has been linked to different GN including anti-GBM up to 10 months after therapy. BRAF inhibition only causes AIN or ATN within 2 months of therapy and is not consistant with the time course of renal injury in our case. Discontinuation of all immunotherapeutic agents and treatment with prednisone and cyclophosphamide stabilized our patient's GFR.