Abstract: FR-PO275
Pauci-Immune Necrotizing and Crescentic Glomerulonephritis due to Pembrolizumab
Session Information
- Onconephrology: From AKI to CKD and Everything in Between
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onconephrology
- 1700 Onconephrology
Authors
- Sharma Divyadarshini, Divya, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States
- Sharma Priamvada, Gargi, East Carolina University, Greenville, North Carolina, United States
Introduction
Immune checkpoint inhibitors (ICI) have trailblazed the treatment of cancer in the past decade. However, these drugs are marred with occurrence of Immune-related Adverse Effects (irAEs). Most commonly reported renal irAE is acute tubulointerstitial nephritis(AIN). Lately, cases of acute kidney injury(AKI) from podocytopathy and glomerulonephritis with ICI are noted but true incidence is likely underestimated from missed diagnosis and under-reporting. We present an illustrative case of an elderly female with a rare manifestation of AKI during treatment with pembrolizumab(Keytruda) with complete recovery due to prompt diagnosis and effective therapy.
Case Description
74-year-old female undergoing treatment for metastatic squamous cell carcinoma of head and neck presented to Nephrology clinic for evaluation of AKI, hematuria and new-onset proteinuria. 15 days ago, she received a third dose of Keytruda. Creatinine had rapidly risen to 2.8mg/dL from baseline 0.5mg/dL. Urine protein-creatinine ratio of 1.6g/g, urine sediment with numerous acanthocytes and RBC casts. Renal biopsy showed acute pauci-immune focal necrotizing glomerulonephritis with 30% cellular crescents, granular mesangial staining for IgM and C3 on immunofluorescence and foot process effacement by electron microscopy. Keytruda was discontinued;she was treated with methylprednisolone, cyclophosphamide and rituximab. Kidney function normalized within 8 weeks.
Discussion
The case highlights importance of clinical suspicion and knowledge of the heterogeneity of pathological findings with renal irAEs on ICI therapy. Emerging data suggest incidence of AKI from 2-20% with Keytruda, a highly selective monoclonal IGg4-kappa antibody against PD – 1 receptor. Renal irAEs can occur during and upto 2 months after therapy cessation. Many times, AKI is presumptively treated with steroids for AIN. The presence of glomerular hematuria, proteinuria or persistent AKI despite steroids warrants a renal biopsy as most patients can recover completely with early diagnosis and prompt treatment and possibly tolerate rechallenge of ICI.
Clockwise:LM Silver stain,Hand lens-biopsy core,LM H&E