Kidney Week

Abstract: SA-PO198

Drug-Induced Thrombotic Microangiopathy from Cancer Therapies: A Clinicopathologic Series

Session Information

• Onconephrology: Kidney Outcomes during Cancer Treatment and Nephropathies
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Onconephrology

• 1700 Onconephrology

Authors

• Pak, Wai Lun Will, Memorial Sloan Kettering Cancer Center, New York, United States

Wai Lun Will Pak, MBBS

• Knezevic, Andrea, Memorial Sloan Kettering Cancer Center Department of Epidemiology & Biostatistics, New York, New York, United States

Andrea Knezevic, MS

• Salvatore, Steven, Weill Cornell Medicine, New York, New York, United States

Steven Salvatore, MD

• Seshan, Surya V., Weill Cornell Medicine, New York, New York, United States

Surya V. Seshan, MBBS

• Glezerman, Ilya, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Ilya Glezerman, MD

• Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States

Edgar A. Jaimes, MD

• Jaffer Sathick, Insara, Memorial Sloan Kettering Cancer Center, New York, New York, United States

Insara Jaffer Sathick, MBBS

Background

Drug-induced thrombotic microangiopathy (di-TMA) is a major sequela of cancer therapies. The diagnosis of di-TMA is often presumptive, making accurate clinical characterization difficult. Herein we present our experience of biopsy-proven renal di-TMA due to cancer therapies.

Methods

We retrospectively reviewed kidney biopsies performed in a cancer center between 2001 and 2023. We included patients with biopsy-proven di-TMA and presentation consistent with a drug-induced process. We describe their clinical, laboratory, pathologic characteristics, and outcomes.

Results

We identified 53 patients with biopsy-proven di-TMA. Median age of this predominantly female (72%) cohort was 64 (range 44-81) years. Primary malignancies were pancreatic (19%), breast (15%), ovarian (15%) and lung (15%) cancers. Primary causative drugs were gemcitabine (49%), bevacizumab (25%), tyrosine kinase inhibitors (19%), and doxorubicin (15%). A secondary drug exposure was implicated in 28% patients. Hypertension was the commonest symptom (81%), followed by edema (53%). Hematological signs were anemia (77%), thrombocytopenia (29%), elevated LDH (67%), and low haptoglobin (46%). AKI occurred in 41 patients (77%), of which 53% was KDIGO stage 1, 20% was stage 2, and 27% was stage 3. Proteinuria occurred in 59% patients, nephrotic range proteinuria in 20% patients. Median creatinine at presentation was 2.0 (1.7-3.1) mg/dL and median eGFR was 29.2 (16.7-37.3) mL/min/1.73m². Majority (84%) had chronic TMA on biopsy, 36% with acute and 13% with subacute features. Cessation of offending drug was the mainstay management in 96%, other treatment included steroids (15%) and eculizumab (8%). Of patients with cessation of drug alone (40, 75%) who experienced AKI (30, 77%), renal recovery was observed in 47% after one year. One out of 9 patients requiring dialysis was weaned off.

Conclusion

We present the largest single institution cohort of patients with biopsy-proven di-TMA from cancer treatment. Though limited by its retrospective nature, our experience suggests that doxorubicin is an underrecognized cause of di-TMA. Many patients had chronic changes on biopsy indicating mild, ongoing endothelial injury before overt TMA develops. Clinical vigilance with early cessation of offending drug may allow for higher rates of renal recovery.

Funding

• Other NIH Support