Suspected Pembrolizumab-Associated Perinuclear Antineutrophil Cytoplasmic Antibody (p-ANCA) Vasculitis With Progressive Kidney Injury in a Patient With Metastatic Renal Cell Carcinoma and Limited Renal Reserve: A Diagnostic Challenge

Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for patients with advanced malignancies but can result in immune-related adverse events involving multiple organ systems. Renal immune-related adverse events most commonly present as acute tubulointerstitial nephritis; however, immune checkpoint inhibitor-associated glomerular diseases, including antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, are rare but potentially severe complications. We report the case of a patient with metastatic clear cell renal cell carcinoma treated with pembrolizumab who developed progressive renal abnormalities, including worsening proteinuria, rising serum creatinine, and newly detected high-titer perinuclear ANCA (p-ANCA) positivity. The patient underwent right nephrectomy in 2019 and subsequent left partial nephrectomy in 2024, resulting in limited renal reserve. Prior to initiation of adjuvant pembrolizumab in April 2024, his serum creatinine was 1.18 mg/dL without significant proteinuria. During subsequent pembrolizumab therapy, his creatinine increased to 1.6 mg/dL and urine protein-to-creatinine ratio increased from 0.2 g/g to 1.2 g/g. Serologic evaluation demonstrated p-ANCA positivity at a titer of 1:640 with negative cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) (<1:20), raising concern for an immune checkpoint inhibitor-associated vasculitic process. Kidney biopsy, the diagnostic gold standard for pauci-immune glomerulonephritis, was deferred due to concern for complications in his solitary partially functioning kidney. Based on the temporal association with pembrolizumab exposure, renal findings, ANCA serology, pulmonary abnormalities, and exclusion of alternative causes, probable pembrolizumab-associated ANCA vasculitis was considered. This case highlights the diagnostic challenges of immune checkpoint inhibitor-associated vasculitis when tissue confirmation cannot safely be obtained and emphasizes the importance of early recognition and multidisciplinary management.