Kidney Week

Abstract: TH-PO1159

Gemcitabine-Induced Thrombotic Microangiopathy Refractory to Complement Inhibition

Session Information

• Onconephrology: Emerging Biomarkers, Preclinical Models, Clinical Challenges, and Therapeutic Strategies
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1600 Onconephrology

Authors

• Choi, Moonyoung, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Moonyoung Choi, MD

• Le, Cindy, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Cindy Le, MD

• Aamir, Nawal, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Nawal Aamir, MD

• Montague, Jahan, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Jahan Montague, MD

• Lee, Sul A, University of Massachusetts Chan Medical School, Worcester, Massachusetts, United States

Sul A Lee, MD, MS, FASN

Introduction

Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and ischemic organ injury. Several pharmacologic agents induce TMA through immune and non-immune mediate with individual susceptibility varying by differences in complement pathway regulation and host endothelial vulnerability. Prior case reports have described successful C5 inhibitor responses in gemcitabine-induced TMA, though the evidence remains limited to small case series. We present a case of biopsy-proven gemcitabine-induced chronic TMA in a patient with cholangiocarcinoma, refractory to complement inhibitor therapy.

Case Description

A 63-year-old female with metastatic intrahepatic cholangiocarcinoma developed multiple episodes of acute kidney injury while on gemcitabine, cisplatin, and durvalumab. Anemia and thrombocytopenia were initially attributed to chemotherapy. Durvalumab was discontinued for possible immune checkpoint inhibitor-induced adrenal insufficiency; cisplatin for severe cytopenias. Gemcitabine monotherapy continued for 4 months (total cumulative dose: 18639 mg). It was held for progressive hemolytic anemia and thrombocytopenia. Despite 4 weeks of discontinuation, TMA parameters worsened: Cr 4.44 mg/dL; Hgb 6.6 g/dL; Plt 72k; LDH 1043 U/L; Haptoglobin <10 mg/dL; PB smear showed schistocytes; spot urine protein-creatinine ratio 7.3 g/g. Serologic workup C3, C4, and ADAMTS13 was unremarkable. Kidney biopsy revealed chronic focally active TMA with diffuse glomerular endotheliosis, without diffuse podocytopathy or immune deposits. Hemodialysis was initiated for volume overload. Despite 6 doses of C5 inhibitor therapy, she remains hemodialysis-dependent, though hematologic indices improved.

Discussion

This case highlights the importance of early recognition and kidney biopsy in gemcitabine-induced TMA, where competing clinical explanations can delay diagnosis. Renal non-response to C5 inhibition likely reflects either established chronic injury at the time of treatment initiation or a mechanism driven predominantly by direct endothelial toxicity rather than primary complement dysregulation. Despite previous case reports on successful response to complement inhibition, larger registry-based studies with detailed clinical, histologic, genetic, and functional complement data are needed to identify which patients with gemcitabine-induced TMA are most likely to benefit from C5 inhibition.