What kind of kidney injury does Tucatinib 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.

How should kidney function be monitored during Tucatinib therapy?

Serum creatinine with a low threshold to add cystatin C if a rise prompts concern; Urinalysis (expected bland) to confirm absence of true injury; LFTs per label (hepatotoxicity is the more clinically relevant toxicity).

How can kidney injury from Tucatinib be prevented?

Anticipate the benign creatinine rise and avoid unnecessary therapy interruption Use cystatin C or measured GFR to confirm preserved true function before stopping effective therapy

Who is at higher risk of kidney injury from Tucatinib?

Baseline CKD (makes the creatinine shift more conspicuous); Concurrent drugs that also inhibit creatinine secretion (e.g., trimethoprim, cimetidine, dolutegravir, cobicistat).

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Printable monograph

HER2 TKI

Tucatinib

Tukysa · TUCA

HER2 TKI · approved 2020 · 4 citations · FAERS AKI reporting ROR 1.70 (95% CI 1.37–2.10, 85 AKI reports)

Recent· through 2024

Fairly sourced5/9 · 5 signals

Not met: 4 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 9y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2024
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.

The textbook 'pseudo-AKI' drug: a creatinine bump from blocked tubular secretion, not real kidney injury.

MildHER2 tyrosine kinase inhibitor

HER2-positive metastatic breast cancer (incl. brain metastases)HER2-positive colorectal cancer

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

A mild creatinine increase is common and expected, but it reflects inhibition of tubular creatinine secretion (a 'pseudo-AKI' artifact) rather than true GFR loss. Dedicated transporter/PK studies show tucatinib inhibits renal OCT2 and MATE1/MATE2-K without changing iohexol-measured GFR.Source: Topletz-Erickson et al., J Clin Pharmacol 2020

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Creatinine rises within the first weeks of therapy, then plateaus and fully reverses within days of stopping.

Distilled from: “Within the first weeks of therapy; plateaus and is fully reversible within days of discontinuation.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. 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.

§03

Kidney injury

Deep divePseudo-AKI: the creatinine rises and the kidney is fineCreatinine does not only filter — a fifth of it is pushed into the urine by tubular transporters, and a drug that blocks those transporters raises the number without touching the glomerulus, producing a rise that looks like acute kidney injury on every axis except the one that matters.

Mechanism of kidney injury

Tucatinib inhibits the renal organic cation transporter OCT2 (basolateral uptake) and MATE1/MATE2-K (apical efflux), which together secrete creatinine from blood into the proximal-tubule lumen. Creatinine is filtered AND secreted; blocking the secretory component raises serum creatinine while filtration (true GFR) is unchanged. This is an artifactual ('pseudo-AKI') rise — confirmed because iohexol-measured GFR is preserved.

Clinical presentation

Modest, early, stable creatinine elevation (often plateaus quickly) with completely bland urinalysis, no electrolyte derangement, no proteinuria, and preserved true GFR (cystatin C / measured GFR unchanged).

Management

Recognize as pseudo-AKI: do not discontinue tucatinib for an isolated stable creatinine rise with bland sediment. Confirm with cystatin C/measured GFR if needed. No specific renal treatment required. The creatinine artifact can also confound capecitabine dose decisions that rely on Cockcroft-Gault.Lesion-level management framework

Risk factors

Baseline CKD (makes the creatinine shift more conspicuous)
Concurrent drugs that also inhibit creatinine secretion (e.g., trimethoprim, cimetidine, dolutegravir, cobicistat)

Prevention

Anticipate the benign creatinine rise and avoid unnecessary therapy interruption
Use cystatin C or measured GFR to confirm preserved true function before stopping effective therapy

Anticancer mechanism· how it treats cancer

Oral, highly HER2-selective tyrosine kinase inhibitor (minimal EGFR activity). Approved with trastuzumab and capecitabine for advanced HER2-positive breast cancer including brain metastases, and with trastuzumab for HER2-positive RAS-wild-type colorectal cancer.

Note · Clinician-flagged as a classic pseudo-AKI / creatinine-secretion artifact. Dedicated transporter PK data support the mechanism.

§04

Clinical depth

Renal dose adjustment

No renal dose adjustment for mild-moderate impairment. The creatinine rise is NOT a reason to reduce tucatinib; but it can falsely lower estimated CrCl and inappropriately trigger capecitabine dose reduction — use cystatin C-based GFR or measured GFR for companion-drug dosing decisions. Limited data in severe impairment, and the label does not recommend the tucatinib + capecitabine + trastuzumab combination at CrCl <30 mL/min — a restriction it attributes to the capecitabine component.

Dialyzability & ESKD dosing

Not characterized; highly protein-bound, hepatically (CYP2C8/3A) cleared small molecule, unlikely to be appreciably dialyzed. No ESKD dosing data.

Differential diagnosis

Pseudo-AKI vs true AKI: a discordant creatinine-up / cystatin C-stable pattern is the signature.

Monitoring

Serum creatinine with a low threshold to add cystatin C if a rise prompts concern
Urinalysis (expected bland) to confirm absence of true injury
LFTs per label (hepatotoxicity is the more clinically relevant toxicity)

Key trials & series

Topletz-Erickson, J Clin Pharmacol 2020 — dedicated renal-transporter/GFR study establishing pseudo-AKI
HER2CLIMB — registrational efficacy trial (clinical context)

Clinical pearls

Cystatin C is the tie-breaker: creatinine up but cystatin C/measured GFR normal = pseudo-AKI, keep treating.
The artifact can sabotage Cockcroft-Gault-based capecitabine dosing — don't dose-reduce the partner drug off a falsely low CrCl.
This is the best-characterized OCT2/MATE creatinine-secretion artifact in oncology — the canonical teaching example.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Pseudo-AKI

§05

References

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

Evidence accrual

4 references · 2015–2024 · 2 since 2022

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.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Nov 2024) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

The use of TUKYSA in combination with capecitabine and trastuzumab is not recommended in patients with severe renal impairment (creatinine clearance [CLcr]: < 30 mL/min estimated by Cockcroft-Gault Equation), because capecitabine is contraindicated in patients with severe renal impairment. Refer to the Full Prescribing Information of capecitabine for additional information in severe renal impairment. No dose adjustment is recommended for patients with mild or moderate renal impairment (CLcr: 30 to 89 mL/min).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 6,932 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· 2 signals

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.

Electrolyte Disturbance

ROR 3.1595% CI 2.73–3.63· 195 reports

SIADH / Hyponatremia

ROR 2.1995% CI 1.69–2.83· 58 reports

FAERS outcomes & reporting trend· 10.2% of reports w/ death · 27.1% w/ hospitalization

10.2%

Reported with a death outcome

708 of 6,932 reports

27.1%

Reported with hospitalization

1,881 of 6,932 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 6,932 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. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 1.7095% CI 1.37–2.10· 85 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Gastrointestinal

Diarrhoea1,766Nausea922Vomiting519Constipation222Stomatitis177

General / constitutional

Fatigue962Asthenia366Pain197Weight Decreased166Malaise162

Skin

Palmar-Plantar Erythrodysaesthesia Syndrome401Rash218Dry Skin165

Nervous system

Headache242Neuropathy Peripheral208Dizziness196

Metabolic & electrolyte

Decreased Appetite314Dehydration269

Musculoskeletal

Pain In Extremity187

Hepatobiliary

Hepatic Enzyme Increased160

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 Tucatinib 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

Entrectinib

Rozlytrek · TRK/ROS1 TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDO

Mild#1 · 89% phenotype match

Larotrectinib

Vitrakvi · TRK inhibitor

Profile

Mild creatinine rise; generally well tolerated.

PSEUDO

Mild#2 · 89% phenotype match

Repotrectinib

Augtyro · ROS1/TRK TKI

Profile

2023 ROS1 inhibitor; creatinine rise via secretion block.

PSEUDO

Mild#3 · 89% phenotype match

Taletrectinib

Ibtrozi · ROS1 TKI

Profile

Next-gen ROS1 TKI; benign transporter-mediated creatinine rise (pseudo-AKI), not true GFR loss.

PSEUDO

Mild#4 · 89% phenotype match

Zongertinib

Hernexeos · HER2 TKI

Profile

HER2 exon20 TKI (2025); creatinine rise likely a secretion artifact.

PSEUDOPRE

Mild#5 · 76% phenotype match

Rucaparib

Rubraca · PARP inhibitor

Profile

Transporter-mediated creatinine rise.

PSEUDO

Mild#6 · 75% phenotype match

Compare Tucatinib 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.