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Updated: Jul 25, 2025
Direct Drug Delivery to Kidney via the Renal Artery
Published on: April 17, 2021
Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity
Benjamin O Adegbite1,2, Matthew H Abramson1, Victoria Gutgarts3
1Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York.
Background:
Dasatinib has been associated with nephrotoxicity. We sought to examine the incidence of proteinuria on dasatinib and determine potential risk factors that may increase dasatinib-associated glomerular injury.
Methods:
We examined glomerular injury through urine albumin-creatinine ratio (UACR) in 82 patients with chronic myelogenous leukemia who were on tyrosine-kinase inhibitor therapy for at least 90 days. t tests were used to compare mean differences in UACR, while regression analysis was used to assess the effects of drug parameters on proteinuria development while on dasatinib. We assayed plasma dasatinib pharmacokinetics using tandem mass spectroscopy and further described a case study of a patient who experienced nephrotic-range proteinuria while on dasatinib.
Results:
Participants treated with dasatinib ( n =32) had significantly higher UACR levels (median 28.0 mg/g; interquartile range, 11.5-119.5) than participants treated with other tyrosine-kinase inhibitors ( n =50; median 15.0 mg/g; interquartile range, 8.0-35.0; P < 0.001). In total, 10% of dasatinib users exhibited severely increased albuminuria (UACR >300 mg/g) versus zero in other tyrosine-kinase inhibitors. Average steady-state concentrations of dasatinib were positively correlated with UACR ( ρ =0.54, P = 0.03) and duration of treatment ( P = 0.003). There were no associations with elevated BP or other confounding factors. In the case study, kidney biopsy revealed global glomerular damage with diffuse foot process effacement that recovered on termination of dasatinib treatment.
Conclusions:
Exposure to dasatinib was associated with a significant chance of developing proteinuria compared with other similar tyrosine-kinase inhibitors. Dasatinib plasma concentration significantly correlated with higher risk of developing proteinuria while receiving dasatinib.
Podcast:
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023_09_08_CJN0000000000000219.mp3.
Insights
Dasatinib use significantly increases the risk of developing proteinuria, a form of kidney damage, compared to other tyrosine kinase inhibitors. Higher dasatinib plasma concentrations correlate with increased proteinuria risk.
Area of Science:
- Nephrology
- Oncology
- Pharmacology
Background:
- Dasatinib, a tyrosine kinase inhibitor, is associated with potential nephrotoxicity.
- Glomerular injury is a concern in patients undergoing tyrosine kinase inhibitor therapy.
Purpose of the Study:
- To investigate the incidence of proteinuria in patients treated with dasatinib.
- To identify risk factors associated with dasatinib-induced glomerular injury.
Main Methods:
- Assessed glomerular injury using urine albumin-creatinine ratio (UACR) in 82 chronic myelogenous leukemia patients on tyrosine kinase inhibitors for at least 90 days.
- Compared UACR levels between dasatinib users and users of other tyrosine kinase inhibitors.
- Analyzed dasatinib plasma pharmacokinetics and correlated drug concentrations with proteinuria development.
- Included a case study of a patient with nephrotic-range proteinuria on dasatinib.
Main Results:
- Dasatinib users (n=32) exhibited significantly higher UACR levels (median 28.0 mg/g) compared to other tyrosine kinase inhibitor users (n=50, median 15.0 mg/g; P < 0.001).
- 10% of dasatinib users showed severely increased albuminuria (UACR >300 mg/g), versus none in the other group.
- Average dasatinib plasma concentrations positively correlated with UACR (ρ=0.54, P=0.03) and treatment duration (P=0.003).
- Kidney biopsy in the case study revealed glomerular damage that resolved upon dasatinib cessation.
Conclusions:
- Dasatinib exposure is linked to a significantly higher incidence of proteinuria compared to other tyrosine kinase inhibitors.
- Elevated dasatinib plasma concentrations are a key risk factor for developing proteinuria during treatment.
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