ALK/ROS1/MET TKI
Crizotinib
Xalkori · CRIZ
An ALK/ROS1/MET inhibitor notable for reversible creatinine rises and the development or growth of complex renal cysts.
MildALK/ROS1/MET tyrosine kinase inhibitor · approved 2011
ALK-positive non-small-cell lung cancerROS1-positive non-small-cell lung cancer
Signature kidney injury
Renal Cysts
Crizotinib commonly causes a reversible rise in serum creatinine and is distinctively associated with the development and progression of complex renal cysts. Peripheral edema and electrolyte disturbances (including hypophosphatemia and hypokalemia) are reported. In real-world ALK-inhibitor cohorts, creatinine-based AKI/CKD events are frequent but mostly mild and reversible; frank kidney failure is uncommon.
Source: Izzedine et al., Invest New Drugs 2016; Pinard et al., Clin Lung Cancer 2025
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / Endothelium
Proximal Tubule
Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water
Renal Cysts
Drug-induced complex renal cysts — the distinctive ALK-inhibitor lesion, classically crizotinib. Usually asymptomatic, dose/duration-related, and they tend to regress when the drug is stopped.
Mechanism of kidney injury
Much of the creatinine increase reflects inhibition of tubular creatinine secretion (a rise in serum creatinine without a true fall in GFR) rather than structural injury. Separately, crizotinib promotes formation and enlargement of complex renal cysts, sometimes with hemorrhage or perinephric extension; the cyst mechanism is incompletely understood and may relate to MET-pathway inhibition in tubular/cyst epithelium.
Clinical presentation
Reversible serum creatinine elevation; new or enlarging complex renal cysts on cross-sectional imaging (which can mimic malignancy or infection); peripheral edema; occasional hypophosphatemia/hypokalemia. Overt AKI is uncommon.
Onset
Creatinine rise often within weeks and reverses on discontinuation; cysts develop and grow over months.
Reversibility
Reversible
Anticancer mechanism
Multitargeted ATP-competitive inhibitor of ALK, ROS1, and MET tyrosine kinases. Used in ALK-positive and ROS1-positive non-small-cell lung cancer.
Management
Most creatinine elevations are benign and reverse on discontinuation; manage cysts conservatively unless complicated (hemorrhage, infection, mass effect). Recognize cysts as a drug effect to avoid mistaking them for progression or new primary malignancy. Reduce dose or interrupt for true AKI, and correct electrolyte disturbances and edema.
Risk factors
- Pre-existing renal cysts or chronic kidney disease
- Longer treatment duration (for cysts)
- Hypertension and male sex (AKI risk factors in ALK-inhibitor cohorts)
- Concurrent nephrotoxins
Prevention
- Monitor serum creatinine and electrolytes (including phosphate)
- Renal imaging surveillance when cysts are detected or suspected
- Distinguish true GFR change from reduced tubular creatinine secretion (consider cystatin C)
Note · Complex renal cysts and a reversible (often secretion-mediated) creatinine rise are the hallmark - distinguish apparent from true GFR decline.
Clinical depth
Renal dose adjustment
No starting-dose change for mild-to-moderate renal impairment (CrCl >=30). For severe renal impairment not on dialysis (CrCl <30), reduce the dose (e.g., to 250 mg once daily) per labeling. Hepatic impairment also requires adjustment.
Dialyzability & ESKD dosing
Highly protein-bound (~91%) and hepatically metabolized; not appreciably dialyzed. ESKD dosing data are limited - use clinical monitoring.
Differential diagnosis
Differentiate the secretion-mediated creatinine rise (true GFR preserved on cystatin C) from genuine AKI, and crizotinib-related complex cysts from cystic renal cell carcinoma, abscess, or metastasis - the temporal link to crizotinib and regression on cessation favor a drug effect.
Monitoring
- Serum creatinine periodically (interpret with secretion artifact in mind)
- Serum phosphate, potassium, and electrolytes
- Renal imaging if cysts are present or suspected
- Cystatin C-based eGFR when true GFR is in question
Key trials & series
- Izzedine et al. ALK-inhibitor renal-effects review
- Pinard et al. real-world ALK-inhibitor AKI/CKD cohort (2025)
Clinical pearls
- Crizotinib cysts can be mistaken for malignancy or progression - recognize them as a class-specific drug effect.
- The creatinine bump is often pseudo-AKI from blocked tubular secretion; confirm true GFR with cystatin C before changing therapy.
- Watch phosphate and potassium - ALK inhibitors can cause electrolyte wasting.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Renal CystsPseudo-AKIPrerenal / Hemodynamic AKIElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of alk/ros1/met tkis.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkThe renal effects of ALK inhibitors.Izzedine H et al. · Invest New Drugs 2016 · PMID 27468827Review detailing crizotinib-associated kidney failure, renal cysts, edema, and electrolyte effects.PMIDAnaplastic lymphoma kinase inhibitors and their effect on the kidney.Bonilla M et al. · Clin Kidney J 2022 · PMID 35892021Updated ALK-inhibitor review covering crizotinib cysts, creatinine rise, and proteinuria.PMIDDevelopment of complex renal cysts: A complication associated with Crizotinib therapy.Chen F et al. · Clin Imaging 2020 · PMID 32353713Case illustrating new complex bilateral cysts on crizotinib that can mimic progression or primary renal malignancy.PMIDCrizotinib-Associated Renal Cysts in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients: A Single-Center Experience.Eiamprapaporn P et al. · Urol Int 2019 · PMID 31480046Case series of crizotinib-associated renal cysts supporting routine cyst monitoring.PMIDReal-World Creatinine-Based Estimates of Acute and Chronic Kidney Dysfunction in Patients with Advanced ALK-Rearranged Non-Small-Cell Lung Cancer Receiving Tyrosine Kinase Inhibitors.Pinard L et al. · Clin Lung Cancer 2025 · PMID 40382267Real-world ALK-inhibitor (including crizotinib) creatinine-based AKI/CKD estimates, mostly reversible.PMIDNew drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int 2015 · PMID 25671763Onco-nephrology review explicitly covering crizotinib renal cysts and creatinine changes.