Bosutinib
Bosulif · BCR-ABL TKI
Reversible eGFR decline.
PSEUDOPRE
MildOpen →
HER2 TKI
Zongertinib
Hernexeos · ZONG
A HER2-selective TKI for lung cancer; renal data are thin, but a benign pseudo-AKI creatinine pattern is plausible.
MildHER2 tyrosine kinase inhibitor · approved 2025
HER2-mutant non-small cell lung cancer
Signature kidney injury
Pseudo-AKI
Renal data are not established. In Beamion LUNG-1 the toxicity profile was mainly low-grade (diarrhea, rash) with no drug-related interstitial lung disease; renal events were not a defining signal. By analogy to other HER2/TKI agents (tucatinib), any creatinine rise is most likely a benign tubular-secretion (pseudo-AKI) effect rather than true injury.
Source: Heymach et al., N Engl J Med 2025
Mechanism of kidney injury
No characterized direct nephron injury. The anticipated renal pattern, by class analogy, is inhibition of proximal-tubule cationic creatinine secretion (OCT2/MATE-type) producing an artifactual creatinine rise without GFR loss; diarrhea could add prerenal volume effects. HER2-selectivity (sparing wild-type EGFR) predicts less of the EGFR-class magnesium wasting.
Clinical presentation
If seen, a modest stable creatinine rise with bland sediment and preserved measured GFR; diarrhea-related volume depletion possible. Structural renal injury has not been described.
Onset
Not established; any creatinine change would emerge during early therapy by class analogy.
Reversibility
Reversible
Anticancer mechanism
Oral, irreversible, HER2-selective tyrosine kinase inhibitor for HER2 (ERBB2)-mutant non-small cell lung cancer; HER2-selectivity is designed to spare wild-type-EGFR-driven skin/GI toxicities and, notably, was associated with no drug-related interstitial lung disease in the pivotal trial. Recently advanced through Beamion LUNG-1 (FDA approval 2025).
Management
Supportive; distinguish pseudo-AKI (stable creatinine, bland sediment, preserved measured GFR) from true injury before stopping therapy, and correct prerenal factors. No drug-specific renal therapy is defined.
Risk factors
- Baseline CKD (makes any creatinine shift more conspicuous)
- Treatment-related diarrhea / volume depletion
- Concurrent drugs affecting creatinine secretion
Prevention
- Monitor creatinine and electrolytes on therapy
- Anticipate a possible benign creatinine rise; confirm true GFR with cystatin C if uncertain
- Manage diarrhea and maintain hydration
Note · Recently FDA-approved (2025) via Beamion LUNG-1, but with no renal-specific literature. The pseudo-AKI framing is class-based prediction (HER2/TKI analogy), supported by the trial's low-grade, non-renal toxicity profile. Treat renal claims as hypothesis-level.
Clinical depth
Renal dose adjustment
Not formally established; as a hepatically metabolized small molecule, meaningful renal-clearance dependence is not expected. A creatinine rise attributable to transporter inhibition should not by itself trigger dose reduction. Data in significant renal impairment/dialysis are absent.
Dialyzability & ESKD dosing
Not characterized; protein-bound, non-renally cleared — unlikely to be appreciably dialyzed. No ESKD dosing guidance.
Differential diagnosis
Anticipated pseudo-AKI (stable creatinine, bland urinalysis, normal cystatin C/measured GFR) vs prerenal AKI from diarrhea (volume-responsive); structural injury is not described. HER2-selectivity makes EGFR-class Mg wasting less likely than with pan-EGFR agents.
Monitoring
- Serum creatinine (with cystatin C to confirm if a rise prompts concern)
- Electrolytes and volume status (diarrhea)
- Standard oncologic toxicity monitoring per label
Key trials & series
- Beamion LUNG-1 (Heymach, NEJM 2025) — pivotal phase 1a/1b; low-grade toxicity, no drug-related ILD
Clinical pearls
- Expect a tucatinib-like benign creatinine pattern by class analogy — confirm with cystatin C rather than stopping therapy.
- HER2-selectivity spares wild-type EGFR, so the EGFR-class magnesium-wasting/skin toxicity should be muted.
- No drug-related ILD in the pivotal trial is a notable safety feature, though not a renal one.
Where it strikes
Nephron segments
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Pseudo-AKIPrerenal / Hemodynamic AKI
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkZongertinib in Previously Treated HER2-Mutant Non-Small-Cell Lung Cancer.Heymach JV et al. · N Engl J Med 2025 · PMID 40293180Pivotal Beamion LUNG-1 results; mainly low-grade (diarrhea, rash) toxicity with no defining renal signal and no drug-related ILD, supporting the conservative renal assessment.LandmarkTucatinib Inhibits Renal Transporters OCT2 and MATE Without Impacting Renal Function in Healthy Subjects.Topletz-Erickson AS et al. · J Clin Pharmacol 2020 · PMID 32989831Class analog (HER2 TKI) establishing the OCT2/MATE-mediated pseudo-AKI creatinine pattern anticipated for zongertinib.PMIDQuantitative Consideration of Clinical Increases in Serum Creatinine Caused by Renal Transporter Inhibition.Nakada T et al. · Drug Metab Dispos 2023 · PMID 36859345Quantitative review explaining how HER2/TKI OCT2/MATE inhibition raises creatinine without true GFR change — the predicted zongertinib pattern.PMIDOnconephrology: mitigation of renal injury in chemotherapy administration.Selamet U et al. · Curr Opin Nephrol Hypertens 2023 · PMID 38095483Onconephrology review distinguishing transporter-mediated creatinine elevation from true TKI nephrotoxicity.