Doxorubicin
Adriamycin · Anthracycline
Experimental podocyte model; clinical proteinuria rare.
GLOM
MildOpen →
BCR-ABL TKI
Dasatinib
Sprycel · DASA
A second-generation BCR-ABL TKI with a distinctive signal of proteinuria and nephrotic-range glomerular injury.
ModerateBCR-ABL tyrosine kinase inhibitor · approved 2006
Chronic myeloid leukemiaPhiladelphia-positive acute lymphoblastic leukemia
Signature kidney injury
Glomerular Injury / Proteinuria
Representative incidence10%
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
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.
Onset
Proteinuria can appear within weeks to months and increases with treatment duration and exposure.
Reversibility
Reversible
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.
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
- Baseline and periodic urine protein/UACR monitoring
- Consider dose reduction or switching TKI if proteinuria develops
- Optimize blood pressure and consider RAAS blockade for persistent proteinuria
Note · Proteinuria/glomerular injury is the signature and a genuinely distinguishing TKI-class signal - monitor urine protein during therapy.
Clinical depth
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.
Where it strikes
Nephron segments
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Glomerular Injury / Proteinuria
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.
LandmarkPatient-Specific Pharmacokinetics and Dasatinib Nephrotoxicity.Adegbite BO et al. · Clin J Am Soc Nephrol 2023 · PMID 37382967Cohort linking dasatinib exposure to albuminuria, with ~10% severely increased UACR and a nephrotic-range case.PMIDDasatinib-induced nephrotic syndrome in a patient with chronic myelogenous leukemia: a case report.Ochiai S et al. · BMC Nephrol 2019 · PMID 30845905Biopsy-proven nephrotic syndrome resolving after switching off dasatinib.PMIDA 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 33431310Nephrotic-range proteinuria with FSGS attributed to dasatinib.PMIDDasatinib-induced pulmonary arterial hypertension.Ozgur Yurttas N et al. · Br J Clin Pharmacol 2018 · PMID 29334406Reviews the SRC/endothelial mechanism of dasatinib vascular toxicity that parallels its glomerular endothelial injury.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology class context for TKI glomerular and other 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 rising contribution of TKIs to drug-induced AKI.
Related agents
Other agents sharing the same signature kidney injury.