How should kidney function be monitored during Trabectedin therapy?

LFTs/bilirubin/alkaline phosphatase and CBC before each cycle; CK/CPK with any myalgia or weakness; Creatinine and electrolytes with muscle symptoms or rising CK; Medication/supplement review for CYP3A4 interactions each visit.

How can kidney injury from Trabectedin be prevented?

Mandatory dexamethasone premedication (20 mg IV before infusion) — reduces hepatic and marrow toxicity Avoid strong CYP3A4 inhibitors and herbal supplements; review medications each cycle Correct hepatic dysfunction before dosing and maintain hydration

Who is at higher risk of kidney injury from Trabectedin?

Hepatic impairment (gates dosing; potentiates toxicity); Concurrent CYP3A4 inhibitors and herbal supplements (e.g. bioflavonoid-rich products); Concurrent statins; Cumulative dosing and volume depletion.

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Printable monograph

Marine alkylating agent

Trabectedin

Yondelis · TRAB

Marine alkylating agent · approved 2015 · 10 citations · FAERS AKI reporting ROR 6.12 (95% CI 5.01–7.49, 99 AKI reports)

Dated evidence· through 2019

Deeply sourced7/9 · 6 signals

Met: 10 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 17y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2019
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 marine minor-groove binder whose kidney injury is indirect — rhabdomyolysis driving pigment nephropathy.

ModerateMarine alkylating agent (ecteinascidin)

Unresectable or metastatic liposarcoma and leiomyosarcoma after an anthracycline-containing regimenRelapsed platinum-sensitive ovarian cancer (in combination, outside the US)

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Representative incidence0.7%

The drug is not directly nephrotoxic and shows no cumulative renal toxicity; clinically important AKI is rare and driven by rhabdomyolysis. The per-cycle rhabdomyolysis rate is not quantified (case-level). The dominant organ toxicity is hepatic — grade 3-4 transaminitis fell from ~34% to ~2% with dexamethasone premedication. Reported rate: rhabdomyolysis in 0.7% — 10,841 trabectedin-treated patients pooled from the Yondelis pharmacovigilance and clinical-trials databases, April… (Grosso 2012, PMID 22484722).Source: Grosso et al., Cancer Chemother Pharmacol 2012

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

Rhabdomyolysis (→ pigment nephropathy) often around the 4th cycle.

Distilled from: “Rhabdomyolysis often around the 4th cycle; hepatotoxicity/myelosuppression nadir ~days 5-15.”

§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.

Acute Tubular Necrosis#1 · Signaturequalitative — no citable incidence
Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

0.7%incidence

SeverityModerate

ReversibilityReversible

Evidence10 citations

Nephron map

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

Distal Tubule / Collecting DuctFine-tuning of Na, K, Mg, acid & water

Tubular Lumen

Acute Tubular Necrosis

Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate.

§03

Kidney injury

Mechanism of kidney injury

Indirect pigment (myoglobinuric) nephropathy: drug-induced rhabdomyolysis releases myoglobin that causes proximal tubular oxidative injury, intratubular heme-pigment cast obstruction, and renal vasoconstriction, producing ATN. The drug itself is not a direct tubular toxin; CYP3A4 inhibitors/herbals and hepatic dysfunction potentiate the muscle injury.

Clinical presentation

Myalgia/weakness with a markedly elevated CK (often >1000 or >5x ULN), myoglobinuria (heme-positive dipstick without red cells), and a rising creatinine; concurrent transaminase elevation, hyperkalemia, hyperphosphatemia, hyperuricemia and hypocalcemia. Rhabdomyolysis often emerges around cycle 4.

Management

Hold the drug; treat rhabdomyolysis with early aggressive IV crystalloid (the cornerstone), correct electrolytes, and use renal replacement therapy if needed. Mannitol/bicarbonate have no proven benefit. Dosing is liver-driven (bilirubin), not kidney-driven.Lesion-level management framework

Risk factors

Hepatic impairment (gates dosing; potentiates toxicity)
Concurrent CYP3A4 inhibitors and herbal supplements (e.g. bioflavonoid-rich products)
Concurrent statins
Cumulative dosing and volume depletion

Prevention

Mandatory dexamethasone premedication (20 mg IV before infusion) — reduces hepatic and marrow toxicity
Avoid strong CYP3A4 inhibitors and herbal supplements; review medications each cycle
Correct hepatic dysfunction before dosing and maintain hydration

Anticancer mechanism· how it treats cancer

Marine-derived tetrahydroisoquinoline alkaloid that binds the DNA minor groove and alkylates guanine N2, bending DNA toward the major groove and poisoning transcription-coupled nucleotide-excision repair; it also disrupts activated transcription and tumor-associated macrophages. Myxoid liposarcoma (FUS-DDIT3 fusion) is especially sensitive.

Note · Established renal mechanism (pigment nephropathy from rhabdomyolysis) supported by case series; no direct tubular toxin and no cumulative renal toxicity.

§04

Clinical depth

Renal dose adjustment

Standard 1.5 mg/m2 IV over 24 h every 3 weeks. Dose modification is gated by bilirubin/hepatic function, not CrCl; avoid in severe hepatic impairment. No established CrCl-based reduction; it has not been studied in CrCl <30 mL/min, so use caution.

Dialyzability & ESKD dosing

Not dialyzable — ~94-98% protein-bound with a large volume of distribution and predominantly biliary elimination (<10% urinary). Dialysis is used to support AKI, not to remove the drug.

Differential diagnosis

Pigment (rhabdomyolysis) ATN — heme-positive dipstick without red cells plus high CK — versus prerenal/sepsis AKI, tumor lysis, contrast nephropathy and hepatorenal physiology. The CK and myoglobinuria pattern identify the mechanism.

Monitoring

LFTs/bilirubin/alkaline phosphatase and CBC before each cycle
CK/CPK with any myalgia or weakness
Creatinine and electrolytes with muscle symptoms or rising CK
Medication/supplement review for CYP3A4 interactions each visit

Key trials & series

Demetri phase III vs dacarbazine (J Clin Oncol 2015) — registrational LPS/LMS trial
Grosso EJC 2006 — dexamethasone premedication markedly reduces hepatic/marrow toxicity

Clinical pearls

Renal injury is indirect — an unexplained creatinine rise with myalgia or dark urine should prompt a CK.
Dexamethasone premedication is mandatory and the most protective single measure.
Screen for CYP3A4 inhibitors and herbal supplements every cycle — they precipitate rhabdomyolysis.
Dosing is liver-driven (bilirubin), not kidney-driven.

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

Class-level context for the major non-renal toxicities of the Marine alkylating agent 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

9 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

9 references · 2002–2019 · 2 since 2017

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.

Case reports — ranked by strength· 1

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseC · LimitedFatal hepatic and renal toxicity as a complication of trabectedin therapy for radiation-induced sarcoma.Pick AM et al. · J Oncol Pharm Pract 2010 · PMID 20015930Patient developed acute kidney injury and renal failure (with hepatic failure) directly attributed to trabectedin after two doses, requiring hemodialysis, fatal outcome.

Conference abstracts & journal reports· 1 non-PubMed

Non-PubMed sources — conference abstracts (e.g. ASN Kidney Week, badged Abstract) and case reports from non-indexed field journals (e.g. Journal of Onco-Nephrology, badged Journal). Included for completeness; weigh below peer-reviewed PubMed citations.

AbstractTrabectedin-Associated AKI: A Case ReportASN Kidney Week 2022 2022 · Abstract SA-PO052Fatal AKI after a single trabectedin dose (peak creatinine 5.39 mg/dL) progressing from a prerenal picture to acute tubular injury with capillary-leak physiology and need for kidney replacement therapy, with rhabdomyolysis not the predominant driver.

FDA label — boxed warning & renal dosing· renal impairment

Quoted verbatim from this agent's current FDA label (Jun 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

No dose adjustment of EVDI is recommended in patients with mild [creatinine clearance (CLcr) 60 to 89 mL/min] or moderate (CLcr of 30 to 59 mL/min) renal impairment. The pharmacokinetics of trabectedin has not been evaluated in patients with severe renal impairment (CLcr <30 mL/min) or end stage renal disease [see Clinical Pharmacology (12.3) ] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 2,310 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· 4 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

Acute Tubular Necrosiscorroborated · ROR 3.7
Electrolyte Disturbancecorroborated · ROR 2.75 — on the terms that name the lesion (ROR 3.28)

Acute Tubular Necrosis

ROR 3.7095% CI 1.39–9.86· 4 reports

SIADH / Hyponatremia

ROR 3.0795% CI 2.10–4.48· 27 reports

Thrombotic Microangiopathy

ROR 2.9495% CI 1.22–7.06· 5 reports

Electrolyte Disturbance

ROR 2.7595% CI 2.12–3.58· 57 reports

FAERS outcomes & reporting trend· 19.3% of reports w/ death · 44.8% w/ hospitalization

19.3%

Reported with a death outcome

445 of 2,310 reports

44.8%

Reported with hospitalization

1,035 of 2,310 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 2,310 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 6.1295% CI 5.01–7.49· 99 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury99

Blood & lymphatic

Neutropenia248Anaemia214Thrombocytopenia202Febrile Neutropenia161Pancytopenia160

Gastrointestinal

Nausea204Vomiting150Diarrhoea89

General / constitutional

Asthenia106Pyrexia103Fatigue99

Hepatobiliary

Alanine Aminotransferase Increased125Aspartate Aminotransferase Increased106Hepatotoxicity67

Immune / infection

Sepsis68Pneumonia67

Musculoskeletal

Rhabdomyolysis132

Respiratory

Dyspnoea66

Guidelines & consensus· 14

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.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.

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 Trabectedin 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

Melphalan flufenamide (melflufen)

Pepaxto · Peptide-conjugated alkylator

Profile

Delivers melphalan intracellularly; BRIDGE supports a reduced 30 mg dose in moderate renal impairment.

ATNLYTE

Moderate#1 · 88% phenotype match

Lurbinectedin

Zepzelca · Marine alkylating agent

Profile

Rhabdomyolysis risk in small-cell lung cancer.

ATNLYTEXTAL

Mild#2 · 78% phenotype match

Telisotuzumab vedotin (Teliso-V)

Emrelis · c-Met ADC (MMAE)

Profile

c-Met MMAE antibody-drug conjugate; proximal tubular ATN risk extrapolated from the ADC/MMAE class.

ATNLYTE

Moderate#3 · 77% phenotype match

Nedaplatin

Aqupla · Platinum agent

Profile

Second-gen platinum with reduced renal toxicity vs cisplatin.

ATNLYTE

Moderate#4 · 75% phenotype match

Plicamycin (mithramycin)

Mithracin · Antitumor antibiotic

Profile

Cumulative tubular ATN; hypocalcemia is an on-target antiresorptive effect.

ATNLYTE

Moderate#5 · 71% phenotype match

Fotemustine

Muphoran · Nitrosourea (alkylating)

Profile

Class delayed cumulative tubulointerstitial/ATN; usually mild; acute signal often really cisplatin.

CINATNLYTE

Moderate#6 · 66% phenotype match

Compare Trabectedin 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 Alkylating agents

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.

Who studies this

The leading contributors to Trabectedin’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Trabectedin; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Soto-Matos, Arturo — their work on Trabectedin, on PubMed (opens in a new tab)2 papers · 21 citesPMID 25171649 (opens PubMed in a new tab)PMID 22484722 (opens PubMed in a new tab)

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 9 clinical records among all 10 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.