Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are widely used in the treatment of advanced breast cancer. While a reversible increase in serum creatinine is a recognized class effect, the spectrum and severity of renal adverse events (AE) associated with these agents remain incompletely characterized.

We conducted a retrospective analysis of the French national pharmacovigilance database from 2016 to January 2024 to identify reports of renal AE associated with the CDK4/6 inhibitors, palbociclib, abemaciclib, and ribociclib. Cases were classified as pseudo-renal failure, renal failure in the context of dehydration, or renal failure without dehydration.

Among 42 cases of renal AE identified, abemaciclib was implicated in 48%, palbociclib in 33%, and ribociclib in 19%. Pseudo-renal failure, attributed to inhibition of tubular creatinine transporters, was observed in one case. Seventeen cases of renal failure occurred in the context of dehydration, predominantly associated with abemaciclib and gastrointestinal toxicity. Twenty-four cases occurred without dehydration, with some confirmed as acute tubular necrosis (ATN) or tubulo-interstitial nephritis (TIN) on biopsy. Most cases were serious and required hospitalization. Renal replacement therapy was needed in three cases. CDK4/6 inhibitor was discontinued in 85% of the cases with a favorable outcome in the majority of the cases. A positive rechallenge was observed in 4 cases including true acute kidney injury in 2 cases.

CDK4/6 inhibitors may cause functional and true renal impairment, ranging from mild, reversible creatinine increases to severe acute kidney injury. When performed, renal biopsy showed ATN and TIN. Close monitoring of renal function including cystatine-C based GFR evaluation and characterization of renal injury are essential to optimize patient safety.