Alectinib
Alecensa · ALK TKI
Creatinine rise via reduced tubular secretion.
PSEUDOPRE
MildOpen →
BCR-ABL TKI
Bosutinib
Bosulif · BOSU
A SRC/ABL TKI associated with a reversible, imatinib-like decline in eGFR over long-term therapy.
MildBCR-ABL tyrosine kinase inhibitor · approved 2012
Chronic myeloid leukemia
Signature kidney injury
Pseudo-AKI
Long-term bosutinib is associated with a gradual, generally reversible decline in eGFR. In a long-term analysis, renal adverse events occurred in roughly 6-13% across lines of therapy, and a notable fraction reached grade 3b or worse eGFR (<45 mL/min/1.73 m2), with many recovering on follow-up; the pattern resembles the eGFR decline seen with imatinib.
Source: Cortes et al., Clin Lymphoma Myeloma Leuk 2017
Mechanism of kidney injury
The eGFR decline appears largely functional/hemodynamic rather than from overt structural injury; it parallels imatinib, is frequently reversible, and may reflect an effect on glomerular filtration/perfusion or on tubular creatinine handling rather than progressive nephron loss. Significant GI toxicity (diarrhea) can also contribute prerenal volume depletion.
Clinical presentation
Gradual rise in creatinine and fall in eGFR over months to years, often asymptomatic and detected on routine monitoring; frequently improves after dose modification or discontinuation. Diarrhea-related volume depletion can produce superimposed prerenal AKI.
Onset
Develops over months of therapy; time to grade 3b eGFR is shortest with later-line use.
Reversibility
Reversible
Anticancer mechanism
Dual SRC/ABL kinase inhibitor of BCR-ABL1 with minimal c-KIT/PDGFR activity, which limits the fluid retention and edema seen with imatinib. Used in chronic, accelerated, or blast-phase CML resistant to or intolerant of prior therapy.
Management
Monitor renal function and adjust dose for significant eGFR decline; the decline is usually reversible, and many patients recover renal function with dose modification. Manage contributing factors such as hypertension, dehydration, and diarrhea.
Risk factors
- Lower baseline eGFR
- Older age and hypertension
- Longer duration / later-line therapy
- Significant diarrhea with volume loss
Prevention
- Monitor creatinine/eGFR at baseline and periodically
- Closer monitoring in patients with pre-existing renal risk factors
- Aggressive antidiarrheal management and hydration; address concurrent nephrotoxins
Note · Reversible eGFR decline mirroring imatinib; not a structural nephrotoxin in the usual case.
Clinical depth
Renal dose adjustment
Per labeling, reduce the starting dose in baseline renal impairment: CrCl 30-50 mL/min use a reduced starting dose (e.g., 400 mg in the resistant/intolerant setting), and CrCl <30 mL/min use a further-reduced dose (e.g., 300 mg). Titrate per response and tolerability.
Dialyzability & ESKD dosing
Highly protein-bound and hepatically metabolized; not expected to be appreciably dialyzed and no supplemental post-dialysis dosing is established. Use clinical judgment in ESKD.
Differential diagnosis
Separate the reversible bosutinib eGFR drift (parallels imatinib, recovers with dose change) from diarrhea-driven prerenal AKI and from intrinsic structural injury (uncommon). Reversibility on dose modification supports a hemodynamic mechanism.
Monitoring
- Serum creatinine/eGFR at baseline and periodically
- Volume status and stool frequency (diarrhea)
- Liver enzymes (hepatotoxicity)
Key trials & series
- Cortes et al. long-term bosutinib renal-function analysis (2017)
- Sonmez et al. TKI eGFR cohort (2024)
Clinical pearls
- Bosutinib’s eGFR decline mirrors imatinib and is usually reversible - monitor, don’t panic.
- Diarrhea is a frequent bosutinib toxicity and a common prerenal contributor; hydrate and treat it.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Pseudo-AKIPrerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of bcr-abl tkis.
Vascular
Hypertension, VTE/ATE, bleeding, aneurysm
- Vascular occlusion (ponatinib), fluid retention
Pulmonary
Pneumonitis, ILD, effusions, hypertension
- Pleural effusions (dasatinib), PAH
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- QT, heart failure
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkEffects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias.Cortes JE et al. · Clin Lymphoma Myeloma Leuk 2017 · PMID 28807791Long-term analysis showing reversible eGFR decline with bosutinib, similar to imatinib.PMIDEffect of Tyrosine Kinase Inhibitor Therapy on Estimated Glomerular Filtration Rate in Patients with Chronic Myeloid Leukemia.Sonmez O et al. · Clin Lymphoma Myeloma Leuk 2024 · PMID 38281820Notes a downward eGFR trend among bosutinib users in a long-term CML cohort.PMIDChanges in estimated glomerular filtration rate in chronic myeloid leukemia patients treated front line with available TKIs and correlation with cardiovascular events.Molica M et al. · Ann Hematol 2018 · PMID 29806063Class context for TKI-associated eGFR change in CML.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology review of TKI renal effects.PMIDPharmacological nephrotoxicity profile in a comprehensive cancer center: What changed in two decades and predictors for the need for haemodialysis and mortality.Ferreira A et al. · Nefrologia (Engl Ed) 2025 · PMID 40783302Cancer-center AKI series documenting the increasing contribution of TKIs to drug-induced AKI.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2024 · PMID 38095483Onconephrology review framing monitoring and mitigation of TKI-associated renal change.