Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
MET inhibitor
Capmatinib
Tabrecta · Capm
A MET inhibitor whose creatinine rise and edema are common but usually mild and reversible.
MildMET inhibitor · approved 2020
MET exon 14 skipping NSCLC
Signature kidney injury
Pseudo-AKI
Representative incidence21%
Increased blood creatinine is a common treatment-related adverse event (~21% in GEOMETRY mono-1; higher in some Asian subsets), and peripheral edema is the single most common adverse event (~47%); most events are grade 1-2 and reversible.
Source: Wolf et al., Lancet Oncol 2024
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
0%incidence
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / Endothelium
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.
Mechanism of kidney injury
MET inhibitors raise serum creatinine largely by inhibiting the renal tubular cation transporters that secrete creatinine (MATE1/MATE2-K, OCT2), producing an apparent creatinine increase without a true fall in GFR — a 'pseudo-AKI' transporter effect. Peripheral edema is a separate, characteristic MET-inhibitor class effect (likely vascular/lymphatic).
Clinical presentation
Mild, often early reversible creatinine elevation with a stable cystatin C-based eGFR; frequent peripheral edema, sometimes facial. No active urinary sediment or proteinuria expected with the transporter effect. Nausea and photosensitivity are other common effects.
Onset
Early — within the first cycles.
Reversibility
Reversible
Anticancer mechanism
Selective MET kinase inhibitor; approved for NSCLC with MET exon 14 skipping mutations.
Management
Usually monitoring; confirm a stable cystatin C before attributing the rise to true AKI or changing dose. Manage edema with supportive measures (limb elevation, diuretics if needed); dose-modify per protocol for grade 3 events or true AKI.
Risk factors
- Pre-existing CKD
- Concurrent transporter-inhibiting or nephrotoxic drugs
Prevention
- Recognize transporter-mediated pseudo-AKI before acting on the number
- Baseline and periodic creatinine
- Use cystatin C-based eGFR if true GFR is uncertain
Note · Creatinine rise is largely a transporter artifact; true nephrotoxicity is uncommon.
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). Dose modifications are driven by edema, ILD/pneumonitis, and hepatotoxicity rather than a CrCl rule.
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, no oliguria) vs true AKI (prerenal, ATN, AIN). A creatinine rise with a flat cystatin C is the hallmark of the MET-inhibitor transporter effect; peripheral edema here is usually drug-related, not nephrotic.
Monitoring
- Serum creatinine at baseline and each cycle; cystatin C-based eGFR if a true GFR change is in question
- Assessment for peripheral edema at each visit
- Liver enzymes and pulmonary symptoms (ILD/pneumonitis) per label
Key trials & series
- GEOMETRY mono-1 (registrational MET exon 14 / MET-amplified NSCLC)
- Seto 2021 Japanese GEOMETRY mono-1 subset (higher creatinine-rise rate)
Clinical pearls
- Check cystatin C before calling a capmatinib creatinine rise AKI — most are transporter-mediated pseudo-AKI.
- Peripheral edema is the single most common AE and is a distinct, often nuisance-level class effect.
- Reserve dose changes for true AKI or grade 3 events, not for an isolated creatinine bump with stable cystatin C.
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.
LandmarkCapmatinib 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 39362249Final GEOMETRY mono-1 safety: increased blood creatinine (~21%) and peripheral edema (~47%) among the most common events.PMIDCapmatinib in Japanese patients with MET exon 14 skipping-mutated or MET-amplified advanced NSCLC: GEOMETRY mono-1 study.Seto T et al. · Cancer Sci 2021 · PMID 33506571Subset analysis with blood creatinine increase (~53%) and peripheral edema as common, mostly grade 1/2 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 35756332Explicitly names MET inhibitors among agents that raise creatinine via tubular-secretion inhibition; cystatin C confirms true GFR.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 40382267Onconephrology cohort showing creatinine-based eGFR changes on lung-cancer TKIs often overstate injury vs cystatin C; most patients continue therapy.PMIDTepotinib: 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 36108212MET-inhibitor class AE-management reference covering the creatinine-increase and peripheral-edema pattern shared with capmatinib.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.