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Clinicopathologic Features of Acute Kidney Injury Associated with Cyclin-Dependent Kinase 4/6 inhib

Shruti Gupta, Tiffany Caza, Sandra M. Herrmann, Vipulbhai C. Sakhiya, Kenar D. Jhaveri.


Selective estrogen receptor inhibitors and aromatase inhibitors are the mainstay of therapy for hormonal receptor-positive (HR+) breast cancer; however, most metastatic HR+, human epidermal growth factor receptor 2-negative (HER2-) progress and acquire resistance to endocrine therapies.1 Cyclin-dependent kinase 4/6 inhibitors (CDK4/6 inhibitors) comprise a new class of drugs that overcome this resistance by blocking the transition from the G1 to S phase of the cell cycle, thereby preventing cell-cycle progression and cancer growth.2 Three CDK4/6 inhibitors—palbociclib, ribociclib, and abemaciclib—have been approved for HER2-negative metastatic breast cancers, usually in combination with hormone therapy. Multiple clinical trials have demonstrated that CDK4/6 inhibitors increase progression-free survival.3–6

The most common adverse events associated with CDK4/6 inhibitors are neutropenia, leukopenia, and fatigue.3,4,6 Acute kidney injury (AKI) is not a well-described complication, with pharmacologic studies suggesting that patients may have a rise in serum creatinine (SCr) without true renal injury.7 Here, we present the first series of patients with biopsy-proven AKI associated with CDK4/6 inhibitors, with a focus on clinical features and pathologic findings.


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