Dasatinib nephrotoxicity correlates with patient-specific pharmacokinetics

Area of Science:

• Nephrology
• Oncology
• Pharmacology

Background:

• Dasatinib, a tyrosine-kinase inhibitor (TKI), is linked to potential nephrotoxicity.
• Understanding the incidence and risk factors for dasatinib-associated glomerular injury is crucial for patient management.

Approach:

• Evaluated glomerular injury using urine albumin-to-creatinine ratio (UACR) in 101 chronic myelogenous leukemia patients on TKI therapy for ≥90 days.
• Assayed plasma dasatinib pharmacokinetics and analyzed a case study of nephrotic-range proteinuria.

Key Points:

• Dasatinib users (n=32) showed significantly higher UACR levels (median 28.0 mg/g) than other TKI users (n=50; median 15.0 mg/g).
• 10% of dasatinib users had severely increased albuminuria (UACR > 300 mg/g) versus none in other TKI groups.
• Higher dasatinib plasma concentrations and longer treatment duration correlated with increased UACR.

Conclusions:

• Dasatinib exposure is associated with a higher incidence of proteinuria compared to other TKIs.
• Plasma dasatinib concentration is a significant risk factor for developing proteinuria.
• Regular screening for renal dysfunction and proteinuria is recommended for all dasatinib patients.