What kind of kidney injury does Larotrectinib 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 Larotrectinib therapy?

Periodic serum creatinine and LFTs (transaminase elevation is the main grade 3 toxicity); Cystatin C if creatinine rises, to distinguish pseudo-AKI from true injury; Neurologic effects (dizziness, gait/cognition).

How can kidney injury from Larotrectinib be prevented?

Recognize the pattern: a modest, stable creatinine rise in an asymptomatic patient Confirm with cystatin C and/or measured GFR before reacting Do not reflexively hold or renally dose-reduce for the isolated finding

Who is at higher risk of kidney injury from Larotrectinib?

Reduced baseline renal reserve (makes a small secretory shift more noticeable); Concurrent OCT2/MATE-inhibiting or nephrotoxic drugs.

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Printable monograph

TRK inhibitor

Larotrectinib

Vitrakvi · LARO

TRK inhibitor · approved 2018 · 7 citations

Aging evidence· through 2020

Fairly sourced4/9 · 4 signals

Met: 7 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2020
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 tumor-agnostic TRK inhibitor whose creatinine bump is pseudo-AKI — blocked tubular secretion, not damage; check cystatin C.

MildTRK inhibitor

Solid tumors with an NTRK gene fusion (tumor-agnostic), metastatic or where surgery would cause severe morbidity, with progression or no satisfactory alternatives

§01

Signature kidney injury

Signature lesion

Pseudo-AKI

The larotrectinib-specific creatinine effect is not separately quantified; the mechanism is extrapolated from the TKI class (the tucatinib OCT2/MATE study and crizotinib's ~21% early, reversible, secretion-driven rise). The clinically important real toxicities are hepatic (transaminase elevation) and neurologic, not renal.Source: Drilon et al., NEJM 2018

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Appears early over days to weeks, stabilizes or plateaus, and is fully reversible on interruption or discontinuation.

Distilled from: “Early (days to weeks), stable/plateauing, and fully reversible on interruption or 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

Mechanism of kidney injury

Pseudo-AKI: the drug inhibits proximal-tubule cation transporters OCT2 (basolateral) and MATE1/MATE2-K (apical) that secrete creatinine into the tubular lumen. Blocking secretion lowers tubular creatinine clearance, raising serum creatinine and lowering creatinine-based eGFR without any reduction in true GFR. Cystatin C (not handled by these transporters) and measured GFR remain normal — an artifactual creatinine elevation, not structural injury.

Clinical presentation

A mild rise in creatinine early after starting (by analogy with related TKIs, within ~2 weeks) that then plateaus, with no oliguria, no electrolyte derangement, a bland urinalysis, no drug-attributable proteinuria, and an asymptomatic patient.

Management

Confirm pseudo-AKI by measuring cystatin C (or measured GFR), which remain normal despite the elevated creatinine; with a bland sediment and no other AKI features, reassure and continue therapy. Reserve workup/interruption for true AKI signals (rapidly rising or large creatinine increase, active sediment, electrolyte abnormalities, proteinuria, symptoms).Lesion-level management framework

Risk factors

Reduced baseline renal reserve (makes a small secretory shift more noticeable)
Concurrent OCT2/MATE-inhibiting or nephrotoxic drugs

Prevention

Recognize the pattern: a modest, stable creatinine rise in an asymptomatic patient
Confirm with cystatin C and/or measured GFR before reacting
Do not reflexively hold or renally dose-reduce for the isolated finding

Anticancer mechanism· how it treats cancer

Highly selective ATP-competitive pan-TRK inhibitor (TRKA/B/C; NTRK1/2/3). In fusion-positive tumors the constitutively active TRK kinase drives oncogenesis; activity is tumor-agnostic, driven solely by the NTRK gene fusion.

Note · No larotrectinib-specific pseudo-AKI case report is indexed in PubMed; the renal-mechanism citations (tucatinib OCT2/MATE, crizotinib, ALK-inhibitor review) are class-level supporting evidence — the honest state of the literature.

§04

Clinical depth

Renal dose adjustment

No dose adjustment is required for mild/moderate renal impairment (no change to the starting dose). Adults 100 mg PO twice daily; children 100 mg/m2 (max 100 mg) twice daily. Moderate-to-severe hepatic impairment does require dose reduction — a useful contrast, since the creatinine bump can be mistaken for a renal-dosing trigger.

Dialyzability & ESKD dosing

Not established; a small-molecule, lipophilic, highly protein-bound drug not expected to be meaningfully dialyzable.

Differential diagnosis

Pseudo-AKI (mild, early, plateauing creatinine; normal cystatin C/measured GFR; bland urine; reversible; asymptomatic — continue drug) versus true AKI to exclude (tumor lysis, prerenal volume depletion, obstruction, concomitant nephrotoxins/contrast), where cystatin C/measured GFR are also reduced, the sediment/proteinuria may be abnormal, and the rise is progressive.

Monitoring

Periodic serum creatinine and LFTs (transaminase elevation is the main grade 3 toxicity)
Cystatin C if creatinine rises, to distinguish pseudo-AKI from true injury
Neurologic effects (dizziness, gait/cognition)

Key trials & series

Pooled registrational analysis (Drilon, NEJM 2018) — phase 1, SCOUT and NAVIGATE; 75% ORR
Expanded pooled analysis (Hong, Lancet Oncol 2020) — 79% ORR with durable safety

Clinical pearls

A small, early, stable creatinine bump usually reflects inhibited tubular creatinine secretion, not damage — check cystatin C before reacting.
Cystatin-C-based eGFR (or measured GFR) is the tiebreaker: normal means pseudo-AKI — reassure and continue; do not reflexively hold or renally dose-reduce.

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 TRK inhibitor 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

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

Evidence accrual

7 references · 2016–2020 · 6 since 2018

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 (May 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

No dose adjustment is recommended for patients with renal impairment of any severity [see Clinical Pharmacology (12.3) ] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 874 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· 18.4% of reports w/ death · 19.5% w/ hospitalization

18.4%

Reported with a death outcome

161 of 874 reports

19.5%

Reported with hospitalization

170 of 874 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 874 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 0.9495% CI 0.42–2.11· 6 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

General / constitutional

Fatigue62Pain43Weight Increased18Fall17Pyrexia16

Nervous system

Dizziness56Neuropathy Peripheral44Paraesthesia19Headache15

Gastrointestinal

Nausea38Vomiting26Diarrhoea23Constipation17

Musculoskeletal

Myalgia27Arthralgia18

Hepatobiliary

Alanine Aminotransferase Increased15Hepatic Enzyme Increased15

Blood & lymphatic

Anaemia21

Skin

Rash21

Respiratory

Dyspnoea15

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 Larotrectinib 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 · 100% phenotype match

Repotrectinib

Augtyro · ROS1/TRK TKI

Profile

2023 ROS1 inhibitor; creatinine rise via secretion block.

PSEUDO

Mild#2 · 100% phenotype match

Taletrectinib

Ibtrozi · ROS1 TKI

Profile

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

PSEUDO

Mild#3 · 99% 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 · 75% phenotype match

Talazoparib

Talzenna · PARP inhibitor

Profile

Renally cleared; creatinine rise.

PSEUDO

Mild#6 · 75% phenotype match

Compare Larotrectinib 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.