Skip to content
Back to full profile

BCR-ABL TKI

Dasatinib

Sprycel · DASA

BCR-ABL TKI · approved 2006 · 7 references

A second-generation BCR-ABL TKI with a distinctive signal of proteinuria and nephrotic-range glomerular injury.

Signature injury
Glomerular Injury / Proteinuria
Severity
Moderate
Reversibility
Reversible
Onset
Proteinuria can appear within weeks to months and increases with treatment duration and exposure.

Signature kidney injury & incidence

Glomerular Injury / Proteinuria — representative incidence ~10%.

Dasatinib causes significantly more albuminuria than other TKIs. In a pharmacokinetic cohort, dasatinib users had higher urine albumin-creatinine ratios and about 10% showed severely increased albuminuria (UACR >300 mg/g) versus none on other TKIs, with the degree of proteinuria correlating with plasma exposure. Nephrotic-range proteinuria with biopsy-proven glomerular injury (FSGS, podocyte foot-process effacement, endothelial injury) is reported in cases.

Source: Adegbite et al., Clin J Am Soc Nephrol 2023

Reported injury signatures: Glomerular Injury / Proteinuria.

Onset timing & rechallenge

Subacute (~1–6 weeks) — Proteinuria appears within weeks to months and increases with treatment duration and exposure.

Mechanism of kidney injury

Off-target inhibition of SRC-family and VEGF/VEGFR-related pro-survival signaling injures the glomerular filtration barrier - the same SRC-pathway and endothelial mechanisms implicated in dasatinib pulmonary arterial hypertension also damage glomerular endothelium and podocytes, producing foot-process effacement, FSGS-pattern lesions, and proteinuria. Plasma dasatinib concentration correlates with the degree of albuminuria, supporting a dose/exposure-dependent podocyte/endothelial effect.

Clinical presentation

Proteinuria ranging from moderate albuminuria to nephrotic-range with edema and hypoalbuminemia; biopsies show foot-process effacement, FSGS, or diffuse glomerular/endothelial injury. Pleural effusions and pulmonary arterial hypertension are characteristic, mechanistically related non-renal effects.

Management

Quantify proteinuria (UACR or UPCR); reduce dose or switch to an alternative TKI (e.g., nilotinib or imatinib) for significant or nephrotic-range proteinuria, and start an ACE inhibitor/ARB for proteinuria reduction. Proteinuria and glomerular injury commonly improve or resolve after dasatinib withdrawal.

Risk factors

  • Higher steady-state dasatinib plasma concentrations
  • Longer treatment duration
  • Pre-existing glomerular disease or proteinuria
  • Concurrent pleural effusion / pulmonary hypertension (shared endothelial toxicity)

Prevention

  • Consider dose reduction or switching TKI if proteinuria develops
  • Optimize blood pressure and consider RAAS blockade for persistent proteinuria

Renal dose adjustment

No formal renal dose adjustment is specified (dasatinib is extensively hepatically metabolized with <4% renal excretion); however, the practical 'renal' adjustment is dose reduction or drug switch when treatment-emergent proteinuria appears.

Dialyzability & ESKD dosing

Dasatinib is highly protein-bound and extensively metabolized; it is not appreciably dialyzed and needs no supplemental post-dialysis dose. Standard dosing applies in ESKD with clinical monitoring.

Differential diagnosis

Dasatinib glomerulopathy (exposure-dependent, reversible on withdrawal, with foot-process effacement) versus primary FSGS, diabetic or hypertensive glomerulosclerosis, and paraprotein-related glomerular disease. The temporal link to dasatinib, exposure correlation, and resolution after switching distinguish it.

Monitoring

  • Urine albumin-creatinine ratio (UACR) at baseline and periodically
  • Serum albumin and edema assessment if proteinuria develops
  • Blood pressure; chest imaging/echocardiography if dyspnea (effusion/PAH)

Key trials & series

  • Adegbite et al. patient-specific PK and dasatinib nephrotoxicity cohort (CJASN 2023)

Clinical pearls

  • Dasatinib is the TKI that causes glomerular proteinuria - check a UACR before and during therapy; it is a genuinely distinguishing class signal.
  • The proteinuria is exposure-dependent and usually reverses on dose reduction or switch to another TKI.
  • Pleural effusion/PAH and glomerular injury share a SRC/endothelial mechanism - their co-occurrence is a clue.

Anticancer mechanism

Potent second-generation inhibitor of BCR-ABL1 and SRC-family kinases (LCK, FYN, YES, SRC), with broader kinase coverage than imatinib and activity against most non-T315I resistance mutations. Used in chronic myeloid leukemia and Ph+ ALL.

Note

Proteinuria/glomerular injury is the signature and a genuinely distinguishing TKI-class signal - monitor urine protein during therapy.

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

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

  1. 1.BCR-ABL tyrosine kinase inhibitors associated acute kidney injury: a pharmacovigilance study based on the FAERS database with a case report.Shi Y, Deng L, Zhu J, et al · BMC Nephrol · 2025 · PMID 41162931
  2. 2.Patient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.Adegbite BO et al. · Clin J Am Soc Nephrol · 2023 · PMID 37382967
  3. 3.Dasatinib-induced nephrotic syndrome in a patient with chronic myelogenous leukemia: a case report.Ochiai S et al. · BMC Nephrol · 2019 · PMID 30845905
  4. 4.A case of dasatinib-induced focal segmental glomerulosclerosis in a patient with Philadelphia chromosome positive chronic myeloid leukemia.Ersoy Yesil E et al. · Nephrol Ther · 2021 · PMID 33431310
  5. 5.Dasatinib-induced pulmonary arterial hypertension.Ozgur Yurttas N et al. · Br J Clin Pharmacol · 2018 · PMID 29334406
  6. 6.New drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int · 2015 · PMID 25671763
  7. 7.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

Case reports & series (2)

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]Dasatinib-induced renal (or chronic) thrombotic microangiopathy in a patient with chronic myeloid leukemia: A case report.Sabour R et al. · SAGE Open Med Case Rep · 2025 · PMID 39967609
  2. C2.[C · Limited]Dasatinib-induced nephrotic-range proteinuria.Wallace E et al. · Am J Kidney Dis · 2013 · PMID 23540262
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.