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

Updated: Mar 14, 2022


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




Introduction

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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