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Pseudo acute kidney injury in patients receiving CDK4/6 inhibitors
Sanne M Buijs1, Elisabeth M Jongbloed2, Lotte E M van Bergen2
1Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. s.buijs@erasmusmc.nl.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusion:
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.
Insights
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) can cause pseudo-acute kidney injury (pseudo-AKI) by affecting creatinine levels. Measuring cystatin C is crucial for accurate kidney function assessment in patients on CDK4/6i therapy.
Area of Science:
- Oncology
- Nephrology
- Pharmacology
Background:
- Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are standard treatment for advanced ER-positive breast cancer, improving progression-free survival.
- CDK4/6i can elevate serum creatinine, potentially indicating kidney injury, but may also inhibit tubular creatinine secretion, leading to pseudo-acute kidney injury (pseudo-AKI).
- The incidence and clinical significance of pseudo-AKI in patients receiving CDK4/6i are not well-established.
Purpose of the Study:
- To determine the incidence of pseudo-AKI in patients with breast cancer treated with CDK4/6i.
- To evaluate the utility of cystatin C measurement in differentiating true AKI from pseudo-AKI.
- To assess the impact of misdiagnosed pseudo-AKI on treatment management.
Main Methods:
- Retrospective single-centre cohort study of breast cancer patients treated with CDK4/6i from January 2017 to December 2023.
- Screening for creatinine increases indicative of AKI within the first six months of treatment, using defined criteria.
- Diagnosis of pseudo-AKI based on estimated glomerular filtration rate (eGFR) calculated using cystatin C compared to baseline and creatinine-based eGFR at the time of creatinine increase.
Main Results:
- Of 234 patients on CDK4/6i, 41 (17.5%) exhibited creatinine levels suggesting AKI.
- Serum cystatin C was available for 22 of these patients; pseudo-AKI was identified in 16 (73%, 95% CI 50-89%).
- In 5 patients (12%), CDK4/6i dose was inappropriately adjusted or treatment was discontinued due to elevated creatinine without true kidney injury.
Conclusions:
- Pseudo-AKI is a common occurrence in patients treated with CDK4/6i, with a high incidence observed in this cohort.
- Measuring eGFR using cystatin C should be considered as an initial diagnostic step when creatinine levels rise during CDK4/6i therapy.
- Accurate differentiation between true AKI and pseudo-AKI is essential to prevent unnecessary treatment modifications.
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