Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
MET inhibitor
Tepotinib
Tepmetko · Tepo
A once-daily MET inhibitor — blood creatinine rise and peripheral edema are its hallmark, manageable effects.
MildMET inhibitor · approved 2021
MET exon 14 skipping NSCLC
Signature kidney injury
Pseudo-AKI
Blood creatinine increase and peripheral edema are the main treatment-related adverse events in the VISION program; both are common and generally mild to moderate and manageable, rarely leading to discontinuation.
Source: Ahn et al., Clin J Oncol Nurs 2022
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.
Onset
Early — within the first cycles.
Reversibility
Reversible
Anticancer mechanism
Highly selective oral MET inhibitor; approved for NSCLC with MET exon 14 skipping alterations.
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.
Risk factors
- Pre-existing CKD
- Concurrent transporter-inhibiting or nephrotoxic drugs
Prevention
- Recognize transporter-mediated creatinine rise before acting on it
- Proactive edema assessment
- Baseline and periodic creatinine; cystatin C if GFR is uncertain
Note · Creatinine rise is largely a transporter artifact; edema is the more clinically bothersome effect.
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.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Pseudo-AKIPrerenal / Hemodynamic AKI
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkTepotinib: 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 36108212Practical review of tepotinib AE management, including creatinine increase and peripheral edema.PMIDTepotinib 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 34037224VISION subset reporting blood creatinine increase and peripheral edema as the most common treatment-related events.PMIDTargeted 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 35756332Mechanistic basis for MET-inhibitor creatinine rise as tubular-secretion inhibition, with cystatin C as confirmatory test.PMIDReal-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 40382267Demonstrates that creatinine-based eGFR changes on lung-cancer TKIs frequently overstate true injury vs cystatin C.PMIDCapmatinib 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 39362249Companion MET-inhibitor registrational dataset confirming the shared blood-creatinine-increase and peripheral-edema signal.PMIDCurrent Trends in Anti-Cancer Molecular Targeted Therapies: Renal Complications and Their Histological Features.Tonooka A et al. · J Nippon Med Sch 2021 · PMID 34840210Onconephrology review of targeted-therapy renal effects.