Pseudo acute kidney injury in patients receiving CDK4/6 inhibitors

Abstract

CDK4/6 inhibitors (CDK4/6i) improve progression-free survival in patients with advanced oestrogen-receptor-positive breast cancer. However, all CDK4/6i may increase creatinine levels, which can indicate kidney injury. In vitro research has shown that CDK4/6i can also inhibit tubular secretion of creatinine, thereby causing the phenomenon ‘pseudo-acute kidney injury (pseudo-AKI)’. The incidence of pseudo-AKI is, however, unknown. We aimed to determine this incidence by assessing cystatin C, a protein filtered in the glomerulus without being subject to tubular secretion, in patients with creatinine increase during CDK4/6i treatment. In this retrospective single-centre cohort study patients with breast cancer who received CDK4/6 inhibitors between January 1st 2017 and December 29th 2023 were screened for the incidence of creatinine increases suggesting potential kidney injury in the first six months of treatment. A significant creatinine increase was defined as 1) a creatinine plasma level of >90 µmol/L in women or >115 µmol/L in men and >10% increase from baseline creatinine plasma level or 2) a creatinine plasma level >1.5 times baseline creatinine or 3) an increase in creatinine plasma level from baseline with >26 µmol/L. Pseudo-AKI was diagnosed if the estimated glomerular filtration rate (eGFR) using cystatin C at the moment of creatinine increase was 1) equal or higher than eGFR using creatinine at baseline and/or 2) at least 25% higher than eGFR using creatinine at the moment of creatinine increase. The primary endpoint was the percentage of patients with pseudo-AKI analysed by means of the binomial probability test. Of the 234 patients treated with a CDK4/6i, 41 (17.5%) had creatinine levels indicating an AKI. From 22 of these 41 patients, cystatin C could be determined in retrospectively available serum. Pseudo-AKI was found in 16 out of 22 patients (73%, 95% CI 50-89%). In 5 out of 41 patients (12%) the CDK4/6i dose was unjustly adjusted or the drug was stopped due to creatinine increase. Pseudo-AKI has a high incidence in patients treated with CDK4/6i. Determining an eGFR based on the cystatin C value should therefore be considered as the first step when creatinine increases during CDK4/6i treatment.