Abstract: FR-PO205
IgG4-Tubulointerstitial Nephritis Due to Pembrolizumab
Session Information
- Onconephrology: Immunotherapy Nephrotoxicity and Assessment of GFR
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Won, Alice H., Memorial Sloan Kettering Cancer Center, New York, New York, United States
- Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States
- Jaffer Sathick, Insara, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Introduction
Immune checkpoint inhibitors (ICIs) such as pembrolizumab have revolutionized cancer treatment by promoting T cell-mediated antitumor response. There have been increasing reports of ICI-related renal toxicity such as acute tubulointerstitial nephritis (ATIN). Here we describe a case of IgG4 tubulointerstitial nephritis (IgG4-TIN) associated with pembrolizumab in a patient with metastatic serous endometrial carcinoma.
Case Description
The patient is a 71-year-old woman with history of hypertension, diabetes mellitus, and serous endometrial carcinoma who had undergone surgical removal, radiation, and chemotherapy (carpoplatin-taxol) with metastatic recurrence to the peritoneum. She was started on pembrolizumab 200 mg every 3 weeks and received 23 doses when she was hospitalized for recurrent acute kidney injury in the setting of urinary tract infection complicated by hydronephrosis. Laboratory findings showed elevated serum creatinine (sCr) of 4.1 mg/dL (from 1.0 mg/dL) with microscopic hematuria, pyuria, and proteinuria (urine protein-creatinine ratio 1.2 g/g). Kidney biopsy was performed due to persistent AKI despite successful stent placement, revealing diffuse tubulointerstitial inflammation with lymphoplasmacytic cell infiltration stained positive for IgG4. Immunoglobulin levels showed elevated IgG (2,347 g/L) and IgG4 (207 g/L) levels. She was started on prednisone 60 mg daily with subsequent improvement in sCr to 2.1 mg/dL, transitioned to a slow taper. At 18-month follow-up, sCr was 1.1mg/dL without any new symptoms. After discontinuing pembrolizumab she was treated with trastuzumab with continued tumor response.
Discussion
Here, we report a novel toxicity of ICIs in the form of IgG4-TIN, which is characterized by rich IgG4-positive plasma cell infiltration as well as serologic abnormalities including elevated serum IgG, IgG4, and IgE. We hypothesize that immune dysregulation induced by ICIs can manifest as IgG4-TIN in rare cases, as observed in our patient. Prompt discontinuation of ICI and initiation of steroid therapy are effective in the management of this complication.