What kind of kidney injury does Datopotamab deruxtecan (Dato-DXd) cause?

Acute Tubular Necrosis — Direct death of tubular epithelial cells — the dose-limiting lesion of the platinums and zoledronate. Other reported patterns: Glomerular Injury / Proteinuria.

How should kidney function be monitored during Datopotamab deruxtecan (Dato-DXd) therapy?

Urinalysis (proteinuria/glucosuria) if creatinine rises; Vigilance for ILD (the priority class toxicity), stomatitis and ocular symptoms; Hydration/intake status.

How can kidney injury from Datopotamab deruxtecan (Dato-DXd) be prevented?

Maintain hydration, especially with stomatitis-related poor intake Hold for unexplained AKI and investigate

Who is at higher risk of kidney injury from Datopotamab deruxtecan (Dato-DXd)?

Pre-existing CKD; Concurrent nephrotoxins; Volume depletion (mucositis-related poor intake); Higher cumulative exposure.

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Printable monograph

Antibody-drug conjugate (TROP2/DXd)

Datopotamab deruxtecan (Dato-DXd)

Datroway · DatoDXd

Antibody-drug conjugate (TROP2/DXd) · approved 2025 · 6 citations

Up to date· through 2025

Fairly sourced5/9 · 5 signals

Met: 6 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
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 2025 TROP2 deruxtecan ADC — proximal-tubular risk extrapolated from the ADC class.

ModerateAntibody-drug conjugate (TROP2/DXd)

HR-positive HER2-negative breast cancerEGFR-mutant non-small-cell lung cancer

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Renal signal is theoretical and not yet quantified, extrapolated from the ADC class. In TROPION-PanTumor01 and the phase III TROPION-Breast01 the dominant toxicities were mucosal (stomatitis ~50%) and ocular events, nausea, and interstitial lung disease; grade ≥3 treatment-related adverse events were lower than chemotherapy (~21%), and kidney-specific events were not prominent.Source: Bardia et al., J Clin Oncol 2024 (TROPION-Breast01)

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Not well characterized given recent approval, but by class analogy a subacute tubular pattern emerges during cumulative dosing.

Distilled from: “Not well characterized (recent approval); by class analogy a subacute tubular pattern during cumulative dosing.”

§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.
Glomerular Injury / ProteinuriaSecondaryqualitative — no citable incidence
Damage to the filtration barrier — podocyte injury, FSGS and protein leak from VEGF and mTOR blockade.

§03

Kidney injury

Mechanism of kidney injury

The class-based concern is proximal-tubular handling of ADC catabolites: filtered or megalin/cubilin-endocytosed conjugate and released membrane-permeable DXd payload could concentrate in proximal tubular epithelial cells and cause topoisomerase-I-mediated tubular injury (acute tubular necrosis). For deruxtecan ADCs specifically, robust human renal data are lacking. Related ADCs provide the precedent for vigilance — e.g., biopsy-proven collapsing FSGS and tubular injury reported with ado-trastuzumab emtansine (T-DM1) — so both a tubular (ATN) and rare glomerular pattern are biologically plausible.

Clinical presentation

If it occurs, a creatinine rise consistent with tubular injury, possibly with low-grade tubular proteinuria, glucosuria or electrolyte wasting; renal events were not a leading toxicity in trials. Watch instead for the characteristic stomatitis, dry eye/keratitis and ILD that dominate the safety profile.

Management

Supportive care and dose modification/hold per label if renal function declines; nephrology input and consideration of biopsy for unexplained or significant AKI to distinguish ATN from a glomerular ADC lesion.Lesion-level management framework

Risk factors

Pre-existing CKD
Concurrent nephrotoxins
Volume depletion (mucositis-related poor intake)
Higher cumulative exposure

Prevention

Maintain hydration, especially with stomatitis-related poor intake
Hold for unexplained AKI and investigate

Anticancer mechanism· how it treats cancer

TROP2 (trophoblast cell-surface antigen 2)-directed antibody-drug conjugate; a humanized anti-TROP2 IgG1 linked via a cleavable tetrapeptide linker to the topoisomerase-I inhibitor payload deruxtecan (DXd, an exatecan derivative). After TROP2 binding and internalization the payload is released and kills the target cell with membrane-permeable bystander activity. Approved for TROP2-expressing HR+/HER2− breast cancer and EGFR-mutant NSCLC.

Note · An emerging, clinician-flagged signal, 2025 approval; the proximal-tubular ATN signature is conservative class extrapolation, not established drug-specific data. The clinically dominant toxicities are mucosal, ocular and pulmonary (ILD), not renal.

§04

Clinical depth

Renal dose adjustment

No dosage adjustment is recommended for CLcr 30 to <90 mL/min; however, the label reports a higher incidence of ILD/pneumonitis in that band, so monitor those patients more closely for respiratory and other adverse reactions. Pharmacokinetics of the ADC and of DXd below CLcr 30 are unknown and ESKD is unstudied. Modify dose/hold for toxicity per label. The antibody component is not renally cleared; small-molecule payload exposure in advanced CKD is not well defined.

Dialyzability & ESKD dosing

The IgG–ADC is not dialyzable; the released small-molecule DXd payload's dialyzability is not characterized. No ESKD dosing guidance — use clinical judgment and close monitoring.

Differential diagnosis

Distinguish potential ADC tubular injury (ATN, bland-to-tubular sediment) from pre-renal AKI driven by mucositis/poor intake, from a glomerular ADC lesion (proteinuria, by analogy to T-DM1 collapsing FSGS), and from concurrent nephrotoxins; biopsy resolves ambiguous significant AKI.

Monitoring

Urinalysis (proteinuria/glucosuria) if creatinine rises
Vigilance for ILD (the priority class toxicity), stomatitis and ocular symptoms
Hydration/intake status

Key trials & series

TROPION-PanTumor01 (Shimizu JCO 2023) first-in-human
TROPION-Breast01 (Bardia JCO 2024) phase III HR+/HER2−
TROPION-Breast02 (TNBC) and TROPION-Lung program

Clinical pearls

The renal signature is class extrapolation — published kidney events with Dato-DXd are not prominent; the real toxicities to watch are ILD, stomatitis and ocular surface disease.
Precedent for ADC renal injury comes from T-DM1 (collapsing FSGS, tubular injury) — keep biopsy on the table for unexplained AKI.
Stomatitis-driven dehydration can cause pre-renal AKI that mimics intrinsic toxicity — assess volume first.
Antibody is not dialyzed; ESKD dosing is undefined — monitor closely.

Where it strikes· nephron segments & injury signatures

Nephron segments

Proximal Tubule

Bulk reabsorption + drug uptake (OCT2, OATs)

Injury signatures

Acute Tubular Necrosis Glomerular Injury / Proteinuria

Beyond the kidney — non-renal toxicities· 4 organ systems

Class-level context for the major non-renal toxicities of the Antibody-drug conjugate (TROP2/DXd) class.

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression (payload-dependent)

Ophthalmic

Keratopathy, uveitis, retinopathy

Keratopathy (belantamab, mirvetuximab, tisotumab)

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Interstitial lung disease (deruxtecan ADCs)

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

Peripheral neuropathy (MMAE payloads)

§05

References

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

Evidence accrual

6 references · 2021–2025 · 5 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 (May 2026) — not paraphrased or interpreted. Full label on DailyMed .

Renal impairment — from the label

Monitor patients with renal impairment for increased adverse reactions, including respiratory reactions. A higher incidence of ILD/pneumonitis has been observed in patients with creatinine clearance (CLcr) 30 to <90 mL/min (estimated by Cockcroft Gault) [see Warnings and Precautions (5.1) ]. No dosage adjustment is recommended in patients with CLcr 30 to <90 mL/min [see Clinical Pharmacology (12.3) ] . The pharmacokinetics of datopotamab deruxtecan-dlnk or DXd in patients with CLcr <30 mL/min is unknown.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 639 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· 21.6% of reports w/ death · 18% w/ hospitalization

21.6%

Reported with a death outcome

138 of 639 reports

18%

Reported with hospitalization

115 of 639 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 639 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 0.2195% CI 0.03–1.52· 1 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Gastrointestinal

Stomatitis103Nausea30Mucosal Inflammation16Oral Pain10

Respiratory

Interstitial Lung Disease26Dyspnoea22Cough19Pneumonitis17

General / constitutional

Fatigue25Weight Decreased17Malaise13Pyrexia9

Eye

Dry Eye22Vision Blurred13Keratitis8

Skin

Rash20Alopecia15

Immune / infection

Infusion Related Reaction16Pneumonia10

Nervous system

Polyneuropathy10

Blood & lymphatic

Neutropenia9

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 Datopotamab deruxtecan (Dato-DXd) 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

Sirolimus

Rapamune · mTOR inhibitor

Profile

Proteinuria, cast nephropathy, delayed graft recovery.

GLOMATN

Moderate#1 · 74% 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#2 · 68% phenotype match

Ibandronate

Boniva · Bisphosphonate

Profile

Lower renal risk than zoledronate.

ATNLYTEGLOM

Mild#3 · 64% phenotype match

Enfortumab vedotin

Padcev · Antibody-drug conjugate (Nectin-4/MMAE)

Profile

Emerging AKI and electrolyte signals in urothelial cancer.

ATNLYTEPRE

Moderate#4 · 61% phenotype match

Trastuzumab deruxtecan

Enhertu · Antibody-drug conjugate (HER2/DXd)

Profile

Emerging AKI/proteinuria reports — under-published.

ATNFANCLYTE

Moderate#5 · 61% phenotype match

Melphalan flufenamide (melflufen)

Pepaxto · Peptide-conjugated alkylator

Profile

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

ATNLYTE

Moderate#6 · 57% phenotype match

Compare Datopotamab deruxtecan (Dato-DXd) 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 Antibody-drug conjugates

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.