MET inhibitor
Tepotinib
Tepmetko · Tepo
MET inhibitor · approved 2021 · 7 references
A once-daily MET inhibitor — blood creatinine rise and peripheral edema are its hallmark, manageable effects.
- Signature injury
- Pseudo-AKI
- Severity
- Mild
- Reversibility
- Reversible
- Onset
- Early — within the first cycles.
Signature kidney injury & incidence
Pseudo-AKI — representative incidence ~25.9%.
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
Reported injury signatures: Pseudo-AKI, Prerenal / Hemodynamic AKI.
Renal toxicity profile
- Pseudo-AKIPrimaryMET-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).
- Prerenal / Hemodynamic AKISecondary
Onset timing & rechallenge
Subacute (~1–6 weeks) — Occurs early, within the first treatment cycles.
Mechanism of kidney injury
Clinical presentation
Management
Risk factors
- Pre-existing CKD
- Concurrent transporter-inhibiting or nephrotoxic drugs
Prevention
- Recognize transporter-mediated creatinine rise before acting on it
Renal dose adjustment
Dialyzability & ESKD dosing
Differential diagnosis
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.
Anticancer mechanism
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.Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management.Veillon R et al. · Clin Lung Cancer · 2022 · PMID 35466070
- 2.Tepotinib: Management of Adverse Events in Patients With MET Exon 14 Skipping Non-Small Cell Lung Cancer.Ahn L et al. · Clin J Oncol Nurs · 2022 · PMID 36108212
- 3.Tepotinib in patients with NSCLC harbouring MET exon 14 skipping: Japanese subset analysis from the Phase II VISION study.Sakai H et al. · Jpn J Clin Oncol · 2021 · PMID 34037224
- 4.Targeted Cancer Therapies Causing Elevations in Serum Creatinine Through Tubular Secretion Inhibition: A Case Report and Review of the Literature.Mach T et al. · Can J Kidney Health Dis · 2022 · PMID 35756332
- 5.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
- 6.Capmatinib in MET exon 14-mutated non-small-cell lung cancer: final results from the open-label, phase 2 GEOMETRY mono-1 trial.Wolf J et al. · Lancet Oncol · 2024 · PMID 39362249
- 7.Current Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch · 2021 · PMID 34840210
Case reports & series (1)
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.
- C1.[B · Moderate]Kidney Injury in Patient with Non-small-cell Lung Cancer Receiving Tepotinib.Oda N et al. · Intern Med · 2025 · PMID 39631863