Skip to content
Back to full profile

BCR-ABL TKI

Bosutinib

Bosulif · BOSU

BCR-ABL TKI · approved 2012 · 6 references

A SRC/ABL TKI associated with a reversible, imatinib-like decline in eGFR over long-term therapy.

Signature injury
Pseudo-AKI
Severity
Mild
Reversibility
Reversible
Onset
Develops over months of therapy; time to grade 3b eGFR is shortest with later-line use.

Signature kidney injury & incidence

Pseudo-AKI — representative incidence ~11% (9–13% range across studies).

Long-term bosutinib is associated with a gradual, generally reversible decline in eGFR. In a long-term analysis, renal adverse events occurred in 9% on first-line and 13% on second-line-or-later bosutinib (the 6% in that analysis is the imatinib comparator arm), 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

Reported injury signatures: Pseudo-AKI, Prerenal / Hemodynamic AKI.

Renal toxicity profile

  1. Pseudo-AKIPrimary~10%Reversible eGFR decline; grade >=3b eGFR (<45) in ~10% first-line and ~24% second-line-or-later bosutinib; ~53-58% recovered to >=45
  2. Prerenal / Hemodynamic AKISecondary

Onset timing & rechallenge

Delayed (>6 weeks / cumulative) — Renal decline develops over months of therapy, with the shortest time to grade 3b eGFR in later-line use.

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.

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

  • Aggressive antidiarrheal management and hydration; address concurrent nephrotoxins

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 and eGFR at baseline (sets the CrCl-banded starting dose) and periodically on therapy; a significant decline prompts dose modification
  • Blood pressure at visits (hypertension is a listed risk factor and a contributing factor to manage)
  • 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.

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.

Note

Reversible eGFR decline mirroring imatinib; not a structural nephrotoxin in the usual case.

Guidelines & consensus

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.Kidney Int · PMID 40975525

References

6 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.Effects of Bosutinib Treatment on Renal Function in Patients With Philadelphia Chromosome-Positive Leukemias.Cortes JE et al. · Clin Lymphoma Myeloma Leuk · 2017 · PMID 28807791
  2. 2.Effect 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 38281820
  3. 3.Changes 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 29806063
  4. 4.New drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int · 2015 · PMID 25671763
  5. 5.Pharmacological 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 40783302
  6. 6.Onconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens · 2024 · PMID 38095483

Case reports & series (3)

The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.

  1. C1.[B · Moderate]Effects of SLC22A2 808G>T polymorphism and bosutinib concentrations on serum creatinine in patients with chronic myeloid leukemia receiving bosutinib therapy.Abumiya M et al. · Sci Rep · 2021 · PMID 33737618
  2. C2.[B · Moderate]Stopping bosutinib reverses bosutinib-induced elevation of serum creatinine in patients with chronic myeloid leukemia.Abumiya M et al. · Int J Hematol · 2025 · PMID 40000571
  3. C3.[C · Limited]Clinical Spectrum of Bosutinib Related Side Effects in a Patient of CML: A Case Report and Review of Literature.Sharma V et al. · Int J Hematol Oncol Stem Cell Res · 2025 · PMID 41281789
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.