What kind of kidney injury does Repotrectinib 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 Repotrectinib therapy?

Baseline and on-treatment serum creatinine (interpret as a step change); Cystatin C / cystatin-C-based eGFR if true GFR is uncertain; Urinalysis to confirm a bland sediment; Review of co-medications affecting OCT2/MATE.

How can kidney injury from Repotrectinib be prevented?

Recognize the pseudo-AKI pattern before reacting Consider cystatin C when true GFR is in question Avoid unnecessary dose changes for an isolated, stable creatinine rise

Who is at higher risk of kidney injury from Repotrectinib?

Pre-existing CKD (complicates interpretation); Concurrent OCT2/MATE-affecting drugs (e.g., metformin, trimethoprim, cimetidine).

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Printable monograph

ROS1/TRK TKI

Repotrectinib

Augtyro · Repo

ROS1/TRK TKI · approved 2023 · 6 citations

Up to date· through 2025

Fairly sourced4/9 · 4 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
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 ROS1/TRK TKI whose creatinine bump often reflects blocked tubular secretion, not true injury.

MildROS1/TRK tyrosine-kinase inhibitor

ROS1-positive NSCLCNTRK-fusion solid tumors

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

An apparent rise in serum creatinine is described that often reflects inhibition of tubular creatinine secretion rather than a true fall in GFR (pseudo-AKI). Genuine intrinsic nephrotoxicity is not a characteristic feature and is not well quantified. This pattern is increasingly recognized across kinase inhibitors (e.g., ALK TKIs, where most creatinine-based eGFR changes do not require treatment change).Source: Van Regemorter et al., Eur J Intern Med 2025 (drug-induced creatinine rise); Topletz-Erickson et al., J Clin Pharmacol 2020 (OCT2/MATE mechanism)

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Appears early after initiation as a stable step change rather than a progressive decline.

Distilled from: “Early after initiation; stable thereafter (a step change, not a progressive decline).”

§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

Mechanism of kidney injury

Creatinine is freely filtered but also actively secreted by proximal-tubular transporters — organic cation transporter 2 (OCT2) at the basolateral membrane and MATE1/MATE2-K at the apical membrane. Several kinase inhibitors inhibit OCT2/MATE-mediated secretion, raising serum creatinine without reducing true glomerular filtration — a benign, reversible 'pseudo-AKI.' Repotrectinib's early creatinine rise is best understood in this framework (the tucatinib OCT2/MATE precedent demonstrates the phenomenon directly). Because cystatin C is not secreted by these transporters, a cystatin-C-based estimate that remains normal confirms preserved true GFR.

Clinical presentation

A modest, early, stable rise in serum creatinine without other features of tubular injury; urinalysis is typically bland (no significant proteinuria, hematuria or casts), and cystatin-C-based eGFR is preserved.

Management

Confirm the pattern: bland urinalysis, an early stable creatinine step, and a normal cystatin-C-based eGFR. No specific renal therapy is needed for transporter-mediated creatinine elevation; reserve dose changes and workup for a true progressive decline, abnormal sediment, or other signs of injury. (Neurologic CNS effects, not renal injury, are repotrectinib's main on-target toxicity.)Lesion-level management framework

Risk factors

Pre-existing CKD (complicates interpretation)
Concurrent OCT2/MATE-affecting drugs (e.g., metformin, trimethoprim, cimetidine)

Prevention

Recognize the pseudo-AKI pattern before reacting
Consider cystatin C when true GFR is in question
Avoid unnecessary dose changes for an isolated, stable creatinine rise

Anticancer mechanism· how it treats cancer

Next-generation, compact macrocyclic ROS1 and NTRK (TRKA/B/C) tyrosine-kinase inhibitor designed to retain activity against solvent-front and other resistance mutations (e.g., ROS1 G2032R). Approved for ROS1-positive NSCLC and NTRK-fusion solid tumors.

Note · The creatinine signal is typically a tubular-secretion-blockade artifact (pseudo-AKI), not true injury; renal-specific literature for repotrectinib is thin, and the concept rests on well-described class behavior. Misreading it as AKI risks unnecessary dose reduction.

§04

Clinical depth

Renal dose adjustment

No renal dose adjustment for mild–moderate impairment; severe impairment/ESKD not well studied. Critically, an isolated transporter-mediated creatinine rise should NOT, by itself, trigger renal dose reduction — confirm true GFR first.

Dialyzability & ESKD dosing

Hepatically metabolized small molecule; dialyzability not characterized and not clinically relevant to the (artifactual) creatinine rise. No established ESKD dosing.

Differential diagnosis

Pseudo-AKI from OCT2/MATE inhibition (early, stable, bland sediment, normal cystatin-C eGFR) vs true AKI (progressive creatinine, abnormal sediment, falling cystatin-C eGFR) vs pre-renal/volume causes; cystatin C is the decisive discriminator.

Monitoring

Baseline and on-treatment serum creatinine (interpret as a step change)
Cystatin C / cystatin-C-based eGFR if true GFR is uncertain
Urinalysis to confirm a bland sediment
Review of co-medications affecting OCT2/MATE

Key trials & series

TRIDENT-1 (registrational ROS1/NTRK trial)
Topletz-Erickson tucatinib OCT2/MATE pharmacology study (class pseudo-AKI proof of concept)
Pinard/Kitchlu ALK-TKI creatinine cohort (analogous kinase-inhibitor creatinine kinetics)

Clinical pearls

An early, stable creatinine bump with a bland urinalysis is usually pseudo-AKI from blocked tubular creatinine secretion — not real injury.
Cystatin C settles the question: it is not OCT2/MATE-secreted, so a normal cystatin-C eGFR confirms preserved true GFR.
Do not dose-reduce reflexively for an isolated creatinine rise — that can under-treat the cancer for an artifact.
Co-meds like metformin, trimethoprim and cimetidine share the OCT2/MATE pathway and can compound the effect.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Pseudo-AKI

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the ROS1/TRK TKI class.

Ophthalmic

Keratopathy, uveitis, retinopathy

Visual disturbance (crizotinib)

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

CNS effects (lorlatinib)

§05

References

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

Evidence accrual

6 references · 2020–2025 · 4 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.

FDA label — boxed warning & renal dosing· renal impairment

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

Renal impairment — from the label

The recommended dosage of AUGTYRO has not been established in patients with severe renal impairment or kidney failure (eGFR <30 mL/min) and patients on dialysis [see Clinical Pharmacology (12.3) ] . No dosage modification is recommended for patients with mild or moderate renal impairment (eGFR 30 to 90 mL/min).

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 250 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.
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 outcomes & reporting trend· 12.4% of reports w/ death · 24.4% w/ hospitalization

12.4%

Reported with a death outcome

31 of 250 reports

24.4%

Reported with hospitalization

61 of 250 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 250 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 0.5595% CI 0.08–3.91· 1 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Nervous system

Dizziness42Neuropathy Peripheral17Paraesthesia10Taste Disorder7Dysgeusia6

Gastrointestinal

Nausea19Constipation7Diarrhoea7

General / constitutional

Fatigue13Pain12Fall6

Musculoskeletal

Muscular Weakness11Myalgia7Arthralgia6

Respiratory

Pulmonary Embolism9Dyspnoea6

Blood & lymphatic

Anaemia8

Skin

Rash6

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 Repotrectinib 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

Taletrectinib

Ibtrozi · ROS1 TKI

Profile

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

PSEUDO

Mild#1 · 100% phenotype match

Entrectinib

Rozlytrek · TRK/ROS1 TKI

Profile

Creatinine rise via reduced tubular secretion.

PSEUDO

Mild#2 · 100% phenotype match

Larotrectinib

Vitrakvi · TRK inhibitor

Profile

Mild creatinine rise; generally well tolerated.

PSEUDO

Mild#3 · 100% phenotype match

Tucatinib

Tukysa · HER2 TKI

Profile

Benign creatinine rise via tubular secretion inhibition.

PSEUDO

Mild#4 · 89% phenotype match

Rucaparib

Rubraca · PARP inhibitor

Profile

Transporter-mediated creatinine rise.

PSEUDO

Mild#5 · 74% phenotype match

Talazoparib

Talzenna · PARP inhibitor

Profile

Renally cleared; creatinine rise.

PSEUDO

Mild#6 · 74% phenotype match

Compare Repotrectinib 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 ALK / ROS1 / MET / TRK 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.