What kind of kidney injury does Zongertinib cause?

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. Other reported patterns: Prerenal / Hemodynamic AKI.

How should kidney function be monitored during Zongertinib therapy?

Serum creatinine (with cystatin C to confirm if a rise prompts concern); Electrolytes and volume status (diarrhea); Standard oncologic toxicity monitoring per label.

How can kidney injury from Zongertinib be prevented?

Anticipate a possible benign creatinine rise; confirm true GFR with cystatin C if uncertain Manage diarrhea and maintain hydration

Who is at higher risk of kidney injury from Zongertinib?

Baseline CKD (makes any creatinine shift more conspicuous); Treatment-related diarrhea / volume depletion; Concurrent drugs affecting creatinine secretion.

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Printable monograph

HER2 TKI

Zongertinib

Hernexeos · ZONG

HER2 TKI · approved 2025 · 4 citations

Up to date· through 2025

Fairly sourced4/9 · 4 signals

Not met: 4 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
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 HER2-selective TKI for lung cancer; renal data are thin, but a benign pseudo-AKI creatinine pattern is plausible.

MildHER2 tyrosine kinase inhibitor

HER2-mutant non-small cell lung cancer

§01

Signature kidney injury

Signature lesion

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

Onset & rechallenge

Time to injuryVariable / unpredictable

Renal onset is not established; any creatinine change would emerge during early therapy by class analogy.

Distilled from: “Not established; any creatinine change would emerge during early therapy by class analogy.”

§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 · Signaturequalitative — no citable incidence
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.
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

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.

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.Lesion-level management framework

Risk factors

Baseline CKD (makes any creatinine shift more conspicuous)
Treatment-related diarrhea / volume depletion
Concurrent drugs affecting creatinine secretion

Prevention

Anticipate a possible benign creatinine rise; confirm true GFR with cystatin C if uncertain
Manage diarrhea and maintain hydration

Anticancer mechanism· how it treats cancer

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 was associated with no drug-related interstitial lung disease in the pivotal trial. Recently advanced through Beamion LUNG-1 (FDA approval 2025).

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.

§04

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.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Pseudo-AKI Prerenal / Hemodynamic AKI

§05

References

4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 2020–2025 · 3 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.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 124 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.

Acute Tubular Necrosis

ROR 17.3395% CI 2.42–124.03· 1 report

FAERS outcomes & reporting trend· 13.7% of reports w/ death · 25% w/ hospitalization

13.7%

Reported with a death outcome

17 of 124 reports

25%

Reported with hospitalization

31 of 124 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 11 systems · 124 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. Showing the top 10 of 11 classified systems; 1 lower-ranked system is not drawn. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 1.1195% CI 0.15–7.95· 1 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Renal & urinary

Blood Creatinine Increased2

Gastrointestinal

Diarrhoea36Nausea8Dry Mouth3Abdominal Discomfort2Constipation2

Skin

Rash8Pruritus3

Hepatobiliary

Hepatic Function Abnormal7Hepatic Cytolysis3

Respiratory

Dyspnoea4Pleural Effusion4

Metabolic & electrolyte

Decreased Appetite6

General / constitutional

Pyrexia3Back Pain2

Blood & lymphatic

Cytopenia4

Nervous system

Dysgeusia2Headache2

Vascular

Epistaxis3

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 Zongertinib 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

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#1 · 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#2 · 89% phenotype match

Abemaciclib

Verzenio · CDK4/6 inhibitor

Profile

Benign creatinine rise via tubular secretion block.

PSEUDOPRE

Mild#3 · 86% phenotype match

Capmatinib

Tabrecta · MET inhibitor

Profile

Reversible creatinine rise and edema.

PSEUDOPRE

Mild#4 · 86% phenotype match

Tepotinib

Tepmetko · MET inhibitor

Profile

Creatinine rise and peripheral edema.

PSEUDOPRE

Mild#5 · 86% phenotype match

Vimseltinib

Romvimza · CSF1R tyrosine kinase inhibitor

Profile

A clean-kidney targeted TKI — watch the CPK, not the nephron.

PSEUDOPRE

Mild#6 · 78% phenotype match

Compare Zongertinib 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 EGFR / HER2 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.