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Published on: March 11, 2016
Effects of crizotinib on creatinine clearance and renal hemodynamics
Lysbert Meijer-Schaap1, John W G Van Putten2, Wilbert M T Janssen1
1Department of General Medicine, Martini Hospital, PO Box 30033, 9700 RM, Groningen, The Netherlands.
Insights
Crizotinib treatment may lead to higher glomerular filtration rate (GFR) than estimated by creatinine. This tyrosine kinase inhibitor may also increase glomerular pressure, potentially risking long-term kidney damage.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- The tyrosine kinase inhibitor crizotinib is used to treat non-small cell lung cancer.
- Crizotinib's impact on renal function is not fully understood.
- Previous chemotherapy regimens, including cisplatin, may influence renal outcomes.
Purpose of the Study:
- To investigate the effects of crizotinib on renal hemodynamics.
- To compare radioactive tracer measurements of renal function with creatinine-based estimates in patients receiving crizotinib.
Main Methods:
- Measured glomerular filtration rate (GFR) and effective renal plasma flow using radioactive tracers in three patients with stage IV non-small cell lung cancer undergoing crizotinib treatment.
- Compared tracer-based GFR with simultaneous creatinine-based measurements.
- Assessed filtration fraction as an indicator of glomerular pressure.
Main Results:
- True GFR was 64-83% higher than creatinine-based estimates in patients treated with crizotinib.
- All patients exhibited increased filtration fraction, indicating elevated glomerular pressure.
- Glomerular pressure further increased in one patient upon follow-up measurement after over a year of crizotinib treatment.
Conclusions:
- Creatinine-based GFR estimates may underestimate true renal function in patients taking crizotinib.
- Elevated glomerular pressure suggests a potential risk of long-term nephrotoxicity associated with crizotinib therapy.
Objectives:
The tyrosine kinase inhibitor crizotinib may affect renal function. The mechanism of this effect is not understood. We aimed to get more insight by measuring renal hemodynamics in patients treated with crizotinib.
Materials And Methods:
Renal hemodynamics (i.e. glomerular filtration rate and effective renal plasma flow) were measured with radioactive tracers in three patients with stage IV non small-cell lung cancer during treatment with crizotinib. The results were compared with simultaneous creatinine based renal function measurements in the same patients.
Results:
Patients had been treated with crizotinib between 155 and 320 days at the first measurement. In one patient the measurement was repeated after a total of one year and two months of treatment. All patients had been treated with chemotherapy containing cisplatin before. In these patients true glomerular filtration rate was 64-83% higher than estimated by creatinine based measurements. Filtration fraction, a measure of glomerular pressure, was increased in all three patients. The glomerular pressure was even further increased in a follow-up measurement.
Conclusion:
Creatinine-based estimates of GFR on crizotinib may underestimate the true GFR. However, evidence of increased glomerular pressure may increase risk of long term true nephrotoxicity.
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