Late-Onset Immune Checkpoint Inhibitor-Associated Nephrotoxicity and Suspected Thrombotic Microangiopathy Following Durvalumab Administration with a Challenging Clinical Course: A Case Report

Abstract

A man in his 60s was diagnosed with distal cholangiocarcinoma after presenting to a local clinic with back pain and weight loss. Gemcitabine plus cisplatin therapy was initiated, and durvalumab was added 10 months later. The patient received 10 cycles of induction therapy after which follow-up contrast-enhanced computed tomography revealed disease progression, prompting the substitution of gemcitabine monotherapy for the original treatment regimen. Following 17 cycles of gemcitabine, the patient developed bilateral lower extremity edema and worsening renal function, leading to hospitalization. Laboratory tests revealed elevated serum creatinine levels, increased tubular injury markers and microscopic hematuria. Based on these findings, the patient’s history of immune checkpoint inhibitor administration, and after excluding other differential diagnoses, our provisional diagnosis was late-onset durvalumab-associated renal injury. Ultrasonography revealed deep vein thrombosis, prompting the initiation of anticoagulant therapy with rivaroxaban. As renal biopsy was contraindicated, empirical steroid therapy was initiated. This initially resulted in decreased serum concentrations of creatinine, N-acetyl-β-D-glucosaminidase, and β₂-microglobulin. However, serum creatinine and β₂-microglobulin levels subsequently increased, accompanied by a sudden and marked decrease in platelet count, indicating gemcitabine-induced thrombotic microangiopathy. To the best of our knowledge, this is the first reported case of coexisting late-onset immune checkpoint inhibitor-related nephrotoxicity and gemcitabine-induced thrombotic microangiopathy, the latter being strongly suspected based on the prevention of rapid renal function deterioration by steroid therapy. Steroid monotherapy was insufficient to achieve full renal recovery from thrombotic microangiopathy, highlighting the need for early recognition and timely intervention when administering gemcitabine to patients with a history of immune checkpoint inhibitor therapy.