What kind of kidney injury does Entrectinib cause?

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.

Is kidney injury from Entrectinib reversible?

Reversible. Typical onset: Within the first weeks of therapy; reversible on discontinuation..

How should kidney function be monitored during Entrectinib therapy?

Serum creatinine with cystatin C as a confirmatory test if a rise prompts concern; Urinalysis (expected bland); QTc and LVEF per label (the clinically important toxicities).

How can kidney injury from Entrectinib be prevented?

Anticipate the benign creatinine rise; avoid unnecessary interruption

Who is at higher risk of kidney injury from Entrectinib?

Baseline CKD (makes the creatinine shift more conspicuous); Concurrent drugs affecting creatinine secretion.

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Printable monograph

TRK/ROS1 TKI

Entrectinib

Rozlytrek · ENTR

TRK/ROS1 TKI · approved 2019 · 7 citations · FAERS AKI reporting ROR 1.67 (95% CI 1.08–2.60, 20 AKI reports)

Recent· through 2024

Fairly sourced5/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Met: Current through 2024
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.

A TRK/ROS1 TKI that nudges creatinine up by curbing tubular secretion — a benign pseudo-AKI pattern.

MildTRK/ROS1 tyrosine kinase inhibitor

NTRK fusion-positive solid tumorsROS1-positive non-small cell lung cancer

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

A mild blood-creatinine increase is recognized and is attributed to reduced tubular creatinine secretion rather than true GFR decline (a pseudo-AKI pattern). It is typically modest, early and reversible; a meaningful structural-AKI rate is not established.Source: Topletz-Erickson et al., J Clin Pharmacol 2020 (transporter analog); Nakada et al., Drug Metab Dispos 2023

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Creatinine change appears within the first weeks of therapy and is reversible on discontinuation.

Distilled from: “Within the first weeks of therapy; reversible on discontinuation.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Pseudo-AKI#1 · Signaturequalitative — no citable incidence
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

Deep divePseudo-AKI: the creatinine rises and the kidney is fineCreatinine does not only filter — a fifth of it is pushed into the urine by tubular transporters, and a drug that blocks those transporters raises the number without touching the glomerulus, producing a rise that looks like acute kidney injury on every axis except the one that matters.

Mechanism of kidney injury

Inhibition of proximal-tubule cationic creatinine transport (OCT2/MATE-type effect, as seen across several TKIs) reduces creatinine secretion into the tubular lumen and raises serum creatinine without injuring the nephron. Filtration (true GFR) is preserved; the change is an analytical/physiologic artifact, not tubular damage.

Clinical presentation

Modest, early, stable creatinine elevation with bland urinalysis and preserved measured GFR (cystatin C unchanged); no electrolyte derangement or proteinuria.

Management

Recognize as pseudo-AKI: do not stop effective therapy for an isolated stable creatinine rise with bland sediment. Confirm with cystatin C/measured GFR if needed. No specific renal treatment.Lesion-level management framework

Risk factors

Baseline CKD (makes the creatinine shift more conspicuous)
Concurrent drugs affecting creatinine secretion

Prevention

Anticipate the benign creatinine rise; avoid unnecessary interruption

Anticancer mechanism· how it treats cancer

Oral, CNS-penetrant multikinase inhibitor of TRK (NTRK1/2/3), ROS1 and ALK. Approved for NTRK fusion-positive solid tumors (tumor-agnostic) and ROS1-positive NSCLC.

Note · Clinician-flagged emerging pseudo-AKI pattern. The creatinine-secretion effect is inferred from the broader TKI literature (tucatinib the proven transporter analog, PMID 32989831) plus class reasoning; the entrectinib exposure-response analysis (Mercier) is cited for dosing/safety context, not as a renal signal.

§04

Clinical depth

Renal dose adjustment

No renal dose adjustment for mild-to-moderate impairment; entrectinib is hepatically (CYP3A4) metabolized with low renal clearance. The creatinine rise should not be misread as AKI requiring dose reduction. Limited data in severe impairment/dialysis.

Dialyzability & ESKD dosing

Not characterized; highly protein-bound, lipophilic, non-renally cleared — unlikely to be appreciably dialyzed. No ESKD dosing guidance.

Differential diagnosis

Pseudo-AKI vs true AKI: discordant creatinine-up / cystatin C-stable is the giveaway for the secretion artifact, not injury.

Monitoring

Serum creatinine with cystatin C as a confirmatory test if a rise prompts concern
Urinalysis (expected bland)
QTc and LVEF per label (the clinically important toxicities)

Key trials & series

Integrated ALKA/STARTRK-1/STARTRK-2 analyses — registrational efficacy/safety (clinical context)
Mercier, Cancer Chemother Pharmacol 2022 — exposure-response analysis supporting the 600 mg/day dose (clinical/safety context)

Clinical pearls

Like tucatinib, entrectinib raises creatinine via blocked proximal-tubular secretion — confirm with cystatin C and keep treating.
The dominant real toxicities are QTc prolongation, weight gain and CNS effects, not the kidney.
Don't dose-reduce or stop for an isolated stable creatinine bump with a bland urinalysis.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Pseudo-AKI

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the TRK/ROS1 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

4 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 2020–2024 · 3 since 2022

Primary (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.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedCase Report: A case of complete response to entrectinib in NTRK fusion gene-positive parotid gland cancer.Moriyama E et al. · Front Oncol 2023 · PMID 37601665Entrectinib caused a rise in serum creatinine at week 68 that promptly reversed with dose reduction, consistent with the drug's pseudo-AKI (reversible creatinine elevation) signature.CaseC · LimitedTRK Inhibition with Entrectinib in Metastatic Salivary Secretory Carcinoma (SC): A Case Report.Ernst MS et al. · Curr Oncol 2022 · PMID 35735423Entrectinib produced an increase in serum creatinine that resolved after dose reduction, illustrating the reversible creatinine rise (pseudo-AKI) characteristic of the drug.CaseC · LimitedEntrectinib-Induced Heart Failure in a Patient With Metastatic Lung Adenocarcinoma: A Case Report.Otsu Y et al. · Cureus 2022 · PMID 36605067Blood creatinine increased early after entrectinib initiation and improved on drug withholding, documenting the reversible creatinine elevation (pseudo-AKI) seen with entrectinib.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Dec 2025) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

No dose adjustment is recommended for patients with mild or moderate renal impairment (CLcr 30 to < 90 mL/min calculated by Cockcroft-Gault equation). ROZLYTREK has not been studied in patients with severe renal impairment (CLcr < 30 mL/min) [see Clinical Pharmacology (12.3) ].

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 1,653 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.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
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· 16.4% of reports w/ death · 21.2% w/ hospitalization

16.4%

Reported with a death outcome

271 of 1,653 reports

21.2%

Reported with hospitalization

350 of 1,653 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 1,653 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.

Disproportionality (acute kidney injury):ROR 1.6795% CI 1.08–2.60· 20 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Blood Creatinine Increased62Renal Impairment60

Nervous system

Dizziness150Taste Disorder71Cognitive Disorder39Dysgeusia36

General / constitutional

Fatigue62Weight Increased52Asthenia40Pain39Oedema34

Gastrointestinal

Constipation66Diarrhoea59Nausea58Vomiting38

Cardiac

Cardiac Failure49

Respiratory

Dyspnoea44

Skin

Rash35

Blood & lymphatic

Pancytopenia32

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 Entrectinib 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.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Larotrectinib

Vitrakvi · TRK inhibitor

Profile

Mild creatinine rise; generally well tolerated.

PSEUDO

Mild#1 · 100% phenotype match

Repotrectinib

Augtyro · ROS1/TRK TKI

Profile

2023 ROS1 inhibitor; creatinine rise via secretion block.

PSEUDO

Mild#2 · 100% phenotype match

Taletrectinib

Ibtrozi · ROS1 TKI

Profile

Next-gen ROS1 TKI; benign transporter-mediated creatinine rise (pseudo-AKI), not true GFR loss.

PSEUDO

Mild#3 · 100% phenotype match

Tucatinib

Tukysa · HER2 TKI

Profile

Benign creatinine rise via tubular secretion inhibition.

PSEUDO

Mild#4 · 89% phenotype match

Rucaparib

Rubraca · PARP inhibitor

Profile

Transporter-mediated creatinine rise.

PSEUDO

Mild#5 · 75% phenotype match

Talazoparib

Talzenna · PARP inhibitor

Profile

Renally cleared; creatinine rise.

PSEUDO

Mild#6 · 75% phenotype match

Compare Entrectinib with its nearest agents

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.

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.