A case of biopsy proven acute tubular injury from cyclin dependent kinase 4/6 inhibitor

Abstract

Cyclin-dependent kinase (CDK) 4/6 inhibitors, combined with endocrine therapy, stand as one of the preferred first-line treatment regimens for patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer. However, data regarding renal toxicities from CDK 4/6 inhibitors is conflicting. Some literature suggests a link to pseudo-acute kidney injury (AKI), while others indicate a potential intrinsic injury. These conflicting findings are compounded by the novelty of the treatment. We report a case of a 66-year-old woman with metastatic breast cancer who developed a true AKI on ribociclib, a CDK4/6 inhibitor. Upon evaluation, her urinalysis demonstrated proteinuria, and her serologic workup (including complements and free light chains) was within normal limits. Her Cystatin C-based eGFR was also found to be decreased. She ultimately underwent a kidney biopsy that demonstrated acute tubular injury (ATI). The etiology of her ATI was thought to be secondary to her CDK 4/6 inhibitor, as other factors causing ATI were ruled out. This case highlights that although much attention is put on CDK 4/6 inhibitors causing pseudo-AKI, it is imperative to ensure that patients are not experiencing true AKIs by assessing kidney function with alternative methods outside of creatinine, such as Cystatin C and exogenous filtration markers such as radionuclides, along with pursuing a renal biopsy when appropriate.