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ALK/ROS1/MET TKI

Crizotinib

Xalkori · CRIZ

ALK/ROS1/MET TKI · approved 2011 · 7 references

An ALK/ROS1/MET inhibitor notable for reversible creatinine rises and the development or growth of complex renal cysts.

Signature injury
Renal Cysts
Severity
Mild
Reversibility
Reversible
Onset
Creatinine rise often within weeks and reverses on discontinuation; cysts develop and grow over months.

Signature kidney injury & incidence

Renal Cysts — representative incidence ~16%.

Crizotinib commonly causes a reversible rise in serum creatinine and is distinctively associated with renal cysts: in the Halpenny series, new or enlarging cysts in 16% (9 of 57 serially imaged patients) and frankly complex cysts in 4% (2 of 57) — the 16% headline is the any-cyst rate, not a complex-cyst or AKI rate. 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: Halpenny et al., Lung Cancer 2017 (renal cysts 16%); Izzedine et al., Invest New Drugs 2016

Reported injury signatures: Renal Cysts, Pseudo-AKI, Electrolyte Disturbance.

Renal toxicity profile

  1. Renal CystsPrimary~16%Renal cyst formation or growth in 16% of crizotinib-treated NSCLC; complex cysts ~4% (retrospective CT cohort)
  2. Pseudo-AKISecondary~12.6%Median eGFR fell ~15% by week 2 (creatinine-secretion effect, not true nephrotoxicity); 12.6% shifted to eGFR <45, largely reversible on discontinuation
  3. Electrolyte DisturbanceRare

Onset timing & rechallenge

Delayed (>6 weeks / cumulative) — Creatinine rises within weeks (reversible on stopping), while the renal cysts develop and enlarge over months.

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.

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

  • Distinguish true GFR change from reduced tubular creatinine secretion (consider cystatin C)

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.

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.

Note

Complex renal cysts and a reversible (often secretion-mediated) creatinine rise are the hallmark - distinguish apparent from true GFR decline.

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.Renal cyst formation in patients treated with crizotinib for non-small cell lung cancer-Incidence, radiological features and clinical characteristics.Halpenny DF et al. · Lung Cancer · 2017 · PMID 28285691
  2. 2.The renal effects of ALK inhibitors.Izzedine H et al. · Invest New Drugs · 2016 · PMID 27468827
  3. 3.Anaplastic lymphoma kinase inhibitors and their effect on the kidney.Bonilla M et al. · Clin Kidney J · 2022 · PMID 35892021
  4. 4.Development of complex renal cysts: A complication associated with Crizotinib therapy.Chen F et al. · Clin Imaging · 2020 · PMID 32353713
  5. 5.Crizotinib-Associated Renal Cysts in Anaplastic Lymphoma Kinase-Positive Lung Cancer Patients: A Single-Center Experience.Eiamprapaporn P et al. · Urol Int · 2019 · PMID 31480046
  6. 6.Real-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 40382267
  7. 7.New drug toxicities in the onco-nephrology world.Perazella MA et al. · Kidney Int · 2015 · PMID 25671763

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.[C · Limited]Bosniak Category III Renal Cysts Caused by Crizotinib in an Anaplastic Lymphoma Kinase Gene-Rearranged Non-Small Cell Lung Cancer Patient.Okubo K et al. · Urology · 2018 · PMID 30142403
  2. C2.[C · Limited]Renal Injury during Long-Term Crizotinib Therapy.Yasuma T et al. · Int J Mol Sci · 2018 · PMID 30257437
  3. C3.[C · Limited]Regression of Crizotinib-Associated Complex Cystic Lesions after Switching to Alectinib.Taima K et al. · Intern Med · 2017 · PMID 28794366

Conference abstracts (1) — non-PubMed, no PMID

  1. A1.Crizotinib-Induced Pseudo-AKI: A Case ReportASN Kidney Week 2019 · SA-PO167Crizotinib (ALK TKI) raised serum creatinine by inhibiting tubular creatinine secretion while true GFR was preserved on Tc-99m-DTPA scintigraphy — a pseudo-AKI to recognize before stopping an effective therapy.
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.