Is kidney injury from Tepotinib reversible?

Reversible. Typical onset: Early — within the first cycles..

How should kidney function be monitored during Tepotinib therapy?

Serum creatinine at baseline and periodically; cystatin C-based eGFR if a true GFR change is in question; Peripheral edema assessment at each visit; Liver enzymes and pulmonary symptoms (ILD/pneumonitis) per label.

How can kidney injury from Tepotinib be prevented?

Recognize transporter-mediated creatinine rise before acting on it

Who is at higher risk of kidney injury from Tepotinib?

Pre-existing CKD; Concurrent transporter-inhibiting or nephrotoxic drugs.

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Printable monograph

MET inhibitor

Tepotinib

Tepmetko · Tepo

MET inhibitor · approved 2021 · 8 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 8 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
Met: Beyond single case reports
Met: High-impact journal
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.

A once-daily MET inhibitor — blood creatinine rise and peripheral edema are its hallmark, manageable effects.

MildMET inhibitor

MET exon 14 skipping NSCLC

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

Representative incidence25.9%

Blood creatinine increase and peripheral edema are the main treatment-related adverse events in the VISION program: in the 255-patient METex14 safety analysis, all-cause creatinine increase occurred in 25.9% and edema — the most common adverse event of clinical interest — in 69.8%. Both are generally mild to moderate and manageable, rarely leading to discontinuation.Source: Veillon et al., Clin Lung Cancer 2022 (VISION safety, creatinine increase 25.9%); Ahn et al., Clin J Oncol Nurs 2022

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Occurs early, within the first treatment cycles.

Distilled from: “Early — within the first cycles.”

§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.

Pseudo-AKI#1 · Signatureno population incidence denominator
MET-inhibitor pseudo-AKI: serum creatinine rose during therapy while cystatin C remained stable, indicating inhibition of renal tubular transporters rather than a GFR fall; creatinine settled on dose reduction (case-documented). PMID 41710007 (opens PubMed in a new tab)
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

25.9%incidence

SeverityMild

ReversibilityReversible

Evidence8 citations

Nephron map

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

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

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

As with capmatinib, the creatinine increase is attributed mainly to inhibition of renal tubular creatinine secretion (MATE/OCT-mediated 'pseudo-AKI') rather than true GFR decline. Peripheral edema is a characteristic MET-inhibitor class effect.

Clinical presentation

Early, mild-to-moderate reversible creatinine elevation with a stable cystatin C-based eGFR; frequent peripheral edema, occasionally with hypoalbuminemia. No active sediment expected; nausea and diarrhea are other common effects.

Management

Monitoring and supportive edema care (limb elevation, diuretics if needed); treatment interruption/dose reduction for grade 3 events or true AKI; distinguish pseudo-AKI from true AKI with cystatin C before changing therapy.Lesion-level management framework

Risk factors

Pre-existing CKD
Concurrent transporter-inhibiting or nephrotoxic drugs

Prevention

Recognize transporter-mediated creatinine rise before acting on it

Anticancer mechanism· how it treats cancer

Highly selective oral MET inhibitor; approved for NSCLC with MET exon 14 skipping alterations.

§04

Clinical depth

Renal dose adjustment

No starting-dose adjustment for mild-moderate renal impairment; severe impairment and dialysis are not well studied (use with caution). Modifications are driven by edema, ILD/pneumonitis, and hepatotoxicity.

Dialyzability & ESKD dosing

Highly protein-bound oral small molecule; not expected to be appreciably dialyzed. No validated ESKD dosing.

Differential diagnosis

Transporter-mediated pseudo-AKI (stable cystatin C, bland urine) vs true AKI; edema from the drug vs from hypoalbuminemia, cardiac, or nephrotic causes. A creatinine rise with a flat cystatin C indicates the transporter effect.

Monitoring

Serum creatinine at baseline and periodically; cystatin C-based eGFR if a true GFR change is in question
Peripheral edema assessment at each visit
Liver enzymes and pulmonary symptoms (ILD/pneumonitis) per label

Key trials & series

VISION (registrational MET exon 14 skipping NSCLC)
Sakai 2021 VISION Japanese subset (creatinine increase and edema most common)
Ahn 2022 AE-management review

Clinical pearls

The creatinine bump is largely a transporter artifact — cystatin C clarifies it and usually permits continued therapy.
Peripheral edema is often the more clinically bothersome effect than the creatinine change.
Reserve dose reduction for grade 3 events or genuine AKI, not for an isolated creatinine rise.

§05

References

7 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

7 references · 2021–2025 · 2 since 2023

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· 1

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.

CaseB · ModerateKidney Injury in Patient with Non-small-cell Lung Cancer Receiving Tepotinib.Oda N et al. · Intern Med 2025 · PMID 39631863Case report of a 68-year-old NSCLC patient on tepotinib with edema, hypoalbuminemia, and elevated creatinine; alongside the known creatinine-transporter-inhibition pseudo-AKI, renal biopsy showed true tubulointerstitial injury from reduced renal blood flow.

FDA label — boxed warning & renal dosing· renal impairment

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

Renal impairment — from the label

No dosage modification is recommended in patients with mild or moderate renal impairment (creatinine clearance [CLcr] 30 to 89 mL/min, estimated by Cockcroft-Gault). The recommended dosage has not been established for 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 642 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.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
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 reported renal phenotypes· 1 signal

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Pseudo-AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

SIADH / Hyponatremia

ROR 2.8695% CI 1.36–6.02· 7 reports

FAERS outcomes & reporting trend· 24.6% of reports w/ death · 26.9% w/ hospitalization

24.6%

Reported with a death outcome

158 of 642 reports

26.9%

Reported with hospitalization

173 of 642 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 642 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 1.5195% CI 0.71–3.17· 7 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Renal & urinary

Renal Impairment52Blood Creatinine Increased23

General / constitutional

Oedema62Oedema Peripheral54Fatigue53Peripheral Swelling36Generalised Oedema11

Gastrointestinal

Diarrhoea57Nausea43Constipation17Vomiting16

Respiratory

Dyspnoea20Interstitial Lung Disease17Pleural Effusion17

Skin

Rash15Pruritus14Alopecia9

Metabolic & electrolyte

Decreased Appetite25Hypoalbuminaemia11

Immune / infection

Pneumonia12

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 Tepotinib 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

Capmatinib

Tabrecta · MET inhibitor

Profile

Reversible creatinine rise and edema.

PSEUDOPRE

Mild#1 · 100% phenotype match

Abemaciclib

Verzenio · CDK4/6 inhibitor

Profile

Benign creatinine rise via tubular secretion block.

PSEUDOPRE

Mild#2 · 89% phenotype match

Alectinib

Alecensa · ALK TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDOPRE

Mild#3 · 89% phenotype match

Ceritinib

Zykadia · ALK TKI

Profile

GI-driven prerenal AKI.

PREPSEUDO

Mild#4 · 89% phenotype match

Vorasidenib

Voranigo · Mutant IDH1/2 inhibitor

Profile

A brain-penetrant IDH inhibitor whose kidney footprint is a benign creatinine bump, not true AKI.

PSEUDOPRE

Mild#5 · 86% phenotype match

Imlunestrant

Inluriyo · Oral selective estrogen-receptor degrader (SERD)

Profile

2025 brain-penetrant oral SERD; renally benign — the only wrinkle is the benign abemaciclib creatinine rise in the combo.

PSEUDOPRE

Mild#6 · 86% phenotype match

Compare Tepotinib 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.