Molecularly Targeted Cancer Medications and Kidney Health

Oral molecularly targeted cancer medications are widely used. Product labels describe an increase in serum creatinine (sCr), potentially due to reversible inhibition of tubular creatinine secretion rather than acute kidney injury.

To determine the 2-year incidence and relative rates of progressive kidney dysfunction in patients treated with molecularly targeted cancer medications associated with an acute change in sCr handling (pseudoacute kidney injury).

Retrospective cohort study of adult patients throughout the San Francisco Bay area treated at Stanford Hospital and clinics since 2008 receiving cyclin dependent kinase 4 or 6 (CDK4/6) inhibitors, poly(adenosine diphosphate-ribose) polymerase inhibitors, and specific drugs within tyrosine kinases inhibitor subgroups with an available estimated glomerular filtration rate (eGFR) from days 1 to 60 after drug start compared with propensity score-matched patients without cancer.

Molecularly targeted cancer medications associated with an acute change in sCr.

Progressive kidney dysfunction defined as a sustained 30% or more decline in eGFR or reaching end-stage kidney disease, accounting for a potentially reversible rise in sCr at drug start by defining baseline eGFR as the mean value from days 1 to 60 after drug start.

Among 5015 patients in the treated cohort, the median (IQR) age was 62 (51-72) years, 3264 (65%) were female, and the mean (SD) baseline eGFR before drug start was 87 (23) mL/min/1.73m2. Using cox proportional hazards regression models, the overall incidence and rate of progressive kidney dysfunction was higher in the treated cohort than in propensity-matched cohorts of patients without cancer (44 vs 38 per 1000 person-years; hazard ratio [HR], 1.4; 95% CI, 1.2-1.6). Rates of kidney dysfunction were higher among patients treated with CDK4/6 inhibitors (HR, 1.9; 95% CI, 1.4-2.6), estimated glomerular filtration rate inhibitors (HR, 1.8; 95% CI, 1.2-2.5), vascular endothelial growth factor receptor inhibitors (HR, 2.1; 95% CI, 1.6-2.7), and B-Raf inhibitors (HR, 1.9; 95% CI, 1.1-3.3) compared with controls. These higher rates persisted in patients without a 20% or more increase in sCr at drug start and without exposure to chemotherapy or immunotherapy.

In this cohort study of patients treated with molecularly targeted anticancer medications associated with an acute rise in sCr, we observed higher incidence and relative rate for kidney dysfunction among treated patients, compared with matched cancer-free patients.