Crizotinib
Xalkori · ALK/ROS1/MET TKI
Reversible creatinine rise and renal cysts.
RCYSTPSEUDOLYTE
Mild#1 · 97% phenotype match
Ensartinib
Ensacove · ALK TKI; pseudo-AKI
ALK TKI · approved 2024 · 5 citations
Up to date· through 2025
Thinly sourced3/9 · 3 signals
- Not met: 5 citations
- Not met: 12+ references
- Not met: Accrued over 10+ years (span: 9y)
- Met: Beyond single case reports
- Not met: Peer-reviewed sources
- Met: Landmark reference
- Met: Current through 2025
- Not met: Real-world FAERS signal
Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.
ALK TKI carrying the ALK-class renal signature of benign creatinine rise and possible renal cysts
MildNext-generation ALK TKI
Locally advanced or metastatic ALK-positive non-small cell lung cancer (NSCLC) in patients who have not previously received an ALK inhibitor
§01
Signature kidney injury
Signature lesion
Representative incidence35.4%
Renal-specific incidence for ensartinib is not separately quantified; in the eXalt3 phase 3 trial serious adverse events, dose reductions, and discontinuations were similar to crizotinib with no new safety signals, and edema and a creatinine rise are described for ensartinib. The renal signature is therefore class-extrapolated from the ALK TKIs, where crizotinib is the index agent for both a benign reduced-tubular-secretion creatinine rise and the development/progression of renal cysts. No defined ensartinib-attributable kidney lesion or incidence rate is established. Reported rate: creatinine elevation in 35.4% — 48 patients with advanced ALK- or ROS1-positive NSCLC enrolled at 2 centers in China and treated with single-agent oral… (Ma 2022, PMID 36647478).Source: Ma et al., J Thorac Dis 2022
Onset & rechallenge
Time to injuryVariable / unpredictable
The benign creatinine rise appears early and stabilizes, whereas ALK-TKI cyst development is a later cumulative finding over months.
Distilled from: “A benign creatinine rise tends to appear early and stabilize; cyst development in the ALK-TKI class is generally a later, cumulative imaging finding over months of therapy.”
§02
Renal toxicities, ranked
This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.
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.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
35.4%incidence
SeverityMild
ReversibilityVariable
Evidence5 citations
Nephron map
Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)
Distal Tubule / Collecting Duct
Pseudo-AKI
The great mimic — a rise in creatinine from blocked tubular secretion (OCT2/MATE), NOT true injury. The GFR is intact; confirm with cystatin C before stopping effective therapy.
§03
Kidney injury
Mechanism of kidney injury
The expected creatinine rise reflects reduced proximal-tubular secretion of creatinine (the OCT2/MATE transporter mechanism shared across many oncology TKIs), producing apparent creatinine elevation without a true GFR drop (pseudo-AKI). Separately, the ALK-TKI class, exemplified by crizotinib, has been associated with the development and progression of simple renal cysts and, less commonly, peripheral edema and electrolyte disturbances; the mechanism of cyst formation is not fully defined. Ensartinib-specific mechanistic renal data are not available, so these pathways are inferred from class behavior.
Clinical presentation
Most commonly an asymptomatic mild creatinine increase on routine monitoring, sometimes accompanied by peripheral edema. New or enlarging renal cysts, when they occur in this class, are usually incidental imaging findings and typically asymptomatic, though hemorrhagic or complex cysts have rarely been reported.
Management
Treat an isolated, stable, mild creatinine rise as likely pseudo-AKI and confirm with cystatin C-based or measured GFR before altering dose. Monitor renal cysts seen on surveillance imaging; most are benign and managed conservatively, but enlarging, complex, or hemorrhagic cysts warrant urology/nephrology input. Manage edema and any electrolyte abnormalities supportively, and reserve dose interruption for genuine, progressive renal decline or symptomatic complications.Lesion-level management framework
Risk factors
- Pre-existing chronic kidney disease or pre-existing renal cysts
- Concurrent nephrotoxins or other tubular-secretion inhibitors
- Volume depletion
- Longer duration of ALK-TKI exposure (for cyst development)
Prevention
- Maintain euvolemia and monitor for edema and electrolyte shifts
Anticancer mechanism· how it treats cancer
Ensartinib is an oral, potent next-generation small-molecule inhibitor of anaplastic lymphoma kinase (ALK). It blocks the ATP-binding site of ALK to shut down oncogenic signaling driven by ALK fusions in NSCLC, with systemic and intracranial activity. In the eXalt3 trial it produced longer progression-free survival and better CNS control than first-generation crizotinib.
§04
Clinical depth
Renal dose adjustment
No CrCl-based renal-impairment dose thresholds are established in the cited literature; consult current product labeling. A benign transporter-mediated creatinine rise should not by itself prompt CrCl-based dose modification.
Dialyzability & ESKD dosing
Not characterized. As a highly protein-bound small-molecule oral TKI, substantial dialytic removal is unlikely, but drug-specific data are lacking.
Differential diagnosis
Separate a benign ALK-TKI creatinine rise (pseudo-AKI) from true AKI (prerenal, ATN from concomitant nephrotoxins, or obstruction). New renal cysts should be distinguished from cystic metastases or pre-existing simple cysts using prior imaging, and edema should be evaluated for cardiac, hepatic, or other drug causes.
Monitoring
- Serum creatinine at baseline and periodically
- Cystatin C-based eGFR or measured GFR when a creatinine rise needs adjudication
- Surveillance cross-sectional imaging reviewed for renal cysts
- Volume status, peripheral edema, and electrolytes
Key trials & series
- eXalt3 (NCT02767804; Horn et al., JAMA Oncol 2021): randomized phase 3 of ensartinib vs crizotinib in ALK-inhibitor-naive ALK-positive NSCLC; median PFS 25.8 vs 12.7 months (HR 0.51) with superior intracranial control and a safety profile similar to crizotinib with no new signals
Clinical pearls
- Anchor ensartinib's renal story to the crizotinib precedent: benign creatinine rise from reduced tubular secretion plus the possibility of renal cysts.
- Review surveillance scans for new or enlarging renal cysts, an ALK-class-specific finding that true injury labs will not capture.
Beyond the kidney — non-renal toxicities· 3 organ systems
Class-level context for the major non-renal toxicities of the ALK TKI class.
Ophthalmic
Keratopathy, uveitis, retinopathy
- Visual disturbance (crizotinib)
Hepatic / Liver
Transaminitis, hepatitis, VOD/SOS
- Transaminitis
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- CNS effects (lorlatinib)
§05
References
5 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
5 references · 2016–2025 · 1 since 2023Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.
- 1.Ensartinib in advanced ALK-positive non-small cell lung cancer: a multicenter, open-label, two-staged, phase 1 trialMa Y et al. · J Thorac Dis · 2022 · PMID 36647478Source of the stored incidence: Ensartinib was well tolerated and common treatment-related adverse events
- 2.LandmarkEnsartinib vs Crizotinib for Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer: A Randomized Clinical Trial.Horn L, Wang Z, Wu G, et al. · JAMA Oncol · 2021 · PMID 34473194The eXalt3 registrational phase 3 trial; establishes efficacy vs crizotinib and the overall safety profile (similar serious AEs, dose reductions, discontinuations; no new safety signals) that frames the renal incidence statement.
- 3.LandmarkThe renal effects of ALK inhibitors.Izzedine H, El-Fekih RK, Perazella MA · Invest New Drugs · 2016 · PMID 27468827Onco-nephrology review of the ALK-TKI class: crizotinib's association with a benign creatinine rise (reduced tubular secretion), renal cysts and their progression, edema, and rare electrolyte disorders, the basis for ensartinib's class-extrapolated renal signature.
- 4.Tucatinib Inhibits Renal Transporters OCT2 and MATE Without Impacting Renal Function in Healthy Subjects.Topletz-Erickson AR, Lee AJ, Mayor JG, et al. · J Clin Pharmacol · 2020 · PMID 32989831Mechanistic demonstration that TKI inhibition of OCT2/MATE-mediated tubular creatinine secretion raises serum creatinine while true GFR is preserved, explaining the pseudo-AKI pattern expected with ensartinib.
- 5.Targeting ROS1 rearrangements in non-small cell lung cancer: Current insights and future directions.Desilets A, Repetto M, Yang SR, Drilon A · Cancer · 2025 · PMID 40171848Context on next-generation fusion-targeted TKIs and the evolution away from first-generation agents such as crizotinib, supporting the class framing of ensartinib's tolerability and off-target profile.
What gets reported — FAERS
Everything below is FAERS — adverse events someone chose to report, about 32 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.
- Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.
FAERS outcomes & reporting trend· 2 of 32 reports w/ death · 7 w/ hospitalization
32 reports is below the 50 this atlas requires before quoting a percentage, so the counts are shown instead of shares.
2 of 32
Reported with a death outcome
too few reports to express as a share
7 of 32
Reported with hospitalization
too few reports to express as a share
Reports per year
- 2015: 0 reports
- 2016: 0 reports
- 2017: 0 reports
- 2018: 0 reports
- 2019: 0 reports
- 2020: 0 reports
- 2021: 2 reports
- 2022: 4 reports
- 2023: 2 reports
- 2024: 6 reports
- 2025: 3 reports
- 2026: 15 reports
Yearly FAERS report volume · most recent year is partial.
FAERS adverse-event signal — all organ systems· 9 systems · 32 reports
Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.
Renal & urinary
Adrenal Insufficiency1Blood Creatinine Increased1
Skin
Rash6Pruritus4Rash Pruritic2Alopecia1
General / constitutional
Fatigue3Oedema3
Gastrointestinal
Constipation3Diarrhoea2
Hepatobiliary
Alanine Aminotransferase Increased2Aspartate Aminotransferase Increased2
Cardiac
Atrial Fibrillation2Arrhythmia1
Metabolic & electrolyte
Decreased Appetite2
Respiratory
Pleural Effusion2
Immune / infection
Anaphylactoid Reaction1
Guidelines & consensus· 13
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.
General onco-nephrology references
ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides 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.SIRMSIRM-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)Radiol Med 2022 · PMID 35303246Recommends 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.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies 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.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses 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.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides 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.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three 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.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes 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.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate 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.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates 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.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates 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.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages 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.
Where Ensartinib sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.
Phenotype-similar agents· the numbered markers on the map above
Profile
Repotrectinib
Augtyro · ROS1/TRK TKI
2023 ROS1 inhibitor; creatinine rise via secretion block.
PSEUDO
Mild#2 · 68% phenotype match
Taletrectinib
Ibtrozi · ROS1 TKI
Next-gen ROS1 TKI; benign transporter-mediated creatinine rise (pseudo-AKI), not true GFR loss.
PSEUDO
Mild#3 · 68% phenotype match
Entrectinib
Rozlytrek · TRK/ROS1 TKI
Creatinine rise via reduced tubular secretion.
PSEUDO
Mild#4 · 68% phenotype match
Larotrectinib
Vitrakvi · TRK inhibitor
Mild creatinine rise; generally well tolerated.
PSEUDO
Mild#5 · 68% phenotype match
Capmatinib
Tabrecta · MET inhibitor
Reversible creatinine rise and edema.
PSEUDOPRE
Mild#6 · 61% phenotype match
Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.
Kidney risk across ALK / ROS1 / MET / TRK inhibitors
Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.
- 1LarotrectinibPSEUDO — Pseudo-AKIMild
- 2RepotrectinibPSEUDO — Pseudo-AKIMild
- 3TaletrectinibPSEUDO — Pseudo-AKIMild
- 4ZidesamtinibPRE — Prerenal / Hemodynamic AKIMild
- 5AlectinibPSEUDO — Pseudo-AKIMild
- 6CapmatinibPSEUDO — Pseudo-AKIMild
- 7CeritinibPRE — Prerenal / Hemodynamic AKIMild
- 8TepotinibPSEUDO — Pseudo-AKIMild
- 9BrigatinibPSEUDO — Pseudo-AKIMild
- 10CrizotinibRCYST — Renal CystsMild
- 11Ensartinib· this agentPSEUDO — Pseudo-AKIMild
- 12LorlatinibPSEUDO — Pseudo-AKIMild
- 13EntrectinibPSEUDO — Pseudo-AKIFAERS AKIMild
A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.