Renal dysfunction in patients with CML on long-term first-line TKI therapy: a single-center analysis

Area of Science:

• Nephrology
• Hematology
• Pharmacology

Background:

• Life expectancy for chronic myeloid leukemia (CML) patients on tyrosine kinase inhibitor (TKI) therapy approaches the general population.
• Long-term toxicities of TKIs, particularly renal effects, require thorough understanding.
• While imatinib's nephrotoxicity is known, the renal safety of newer TKIs (dasatinib, nilotinib, flumatinib) is less characterized.

Purpose of the Study:

• To compare the long-term renal safety profiles of four first-line TKIs used in CML treatment.
• To analyze renal function trajectories and the incidence of renal adverse events across different TKI treatment groups.

Main Methods:

• Retrospective analysis of renal function (serum creatinine, eGFR) in 348 CML patients.
• Utilized mixed-effects models to compare eGFR trajectories across imatinib, dasatinib, nilotinib, and flumatinib groups.
• Evaluated chronic renal adverse events (CRAE) and acute kidney injury (AKI).

Main Results:

• Significant differences in eGFR trajectories were observed among the four TKIs.
• Imatinib and flumatinib groups showed significant creatinine elevation and eGFR decline.
• Dasatinib and nilotinib groups exhibited different patterns, with nilotinib showing a decline and dasatinib a slight increase in eGFR. Flumatinib was associated with all reported AKI cases.
• Treatment-free remission did not significantly improve renal function, suggesting potential irreversibility of damage.

Conclusions:

• TKIs possess distinct renal safety profiles.
• Individualized TKI selection considering baseline renal status is crucial.
• Rigorous renal monitoring throughout TKI therapy is essential for CML management.