How should kidney function be monitored during Trastuzumab deruxtecan therapy?

Serum electrolytes (K, phosphate, magnesium, bicarbonate) and creatinine each cycle; Urinalysis for glucosuria/proteinuria if tubular wasting is suspected; Pulmonary symptoms/imaging for interstitial lung disease (the dominant labeled organ toxicity).

How can kidney injury from Trastuzumab deruxtecan be prevented?

Maintain hydration and manage diarrhea

Who is at higher risk of kidney injury from Trastuzumab deruxtecan?

Concurrent GI toxicity/dehydration; Pre-existing CKD; Concurrent nephrotoxins.

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Printable monograph

Antibody-drug conjugate (HER2/DXd)

Trastuzumab deruxtecan

Enhertu · T-DXd

Antibody-drug conjugate (HER2/DXd) · approved 2019 · 6 citations

Up to date· through 2026

Fairly sourced4/9 · 4 signals

Met: 6 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 9y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Met: Current through 2026
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 HER2/DXd conjugate with emerging, under-published renal signals — including a reported reversible Fanconi syndrome.

ModerateAntibody-drug conjugate

HER2-positive breast cancerHER2-low breast cancerGastric cancerHER2-expressing solid tumors

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Renal data are emerging and under-published. AKI/proteinuria are reported at case level; a reversible proximal-tubule Fanconi syndrome (glucosuria, phosphate/potassium wasting, non-anion-gap acidosis) has been described and attributed to the deruxtecan payload. Renal-specific incidence is not quantified.Source: Kalantri & Lomashvili, Cureus 2023 (case)

Onset & rechallenge

Time to injuryVariable / unpredictable

Reported during ongoing therapy, sometimes resolving over months after discontinuation.

Distilled from: “Variable; reported during ongoing therapy, sometimes resolving over months after discontinuation.”

§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.
Fanconi SyndromeSecondaryqualitative — no citable incidence
Global failure of proximal tubule reabsorption — glucosuria, phosphaturia and acidosis, classically from ifosfamide.
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.

Incidence not quantified

SeverityModerate

ReversibilityVariable

Evidence6 citations

Nephron map

Proximal TubuleBulk reabsorption + drug uptake (OCT2, OATs)

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

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

Proposed proximal tubular injury from off-target uptake of the membrane-permeable DXd payload (the same bystander property that drives anti-tumor activity), producing a tubular/ATN- or Fanconi-pattern picture with impaired proximal reabsorption of glucose, phosphate, potassium and bicarbonate. GI toxicity (diarrhea) can add a prerenal component. The human renal mechanism remains poorly characterized.

Clinical presentation

When renal involvement occurs: tubular electrolyte wasting (hypokalemia, hypophosphatemia, hypomagnesemia), non-anion-gap metabolic acidosis, glucosuria with normoglycemia and proteinuria (Fanconi pattern), or a creatinine rise; the picture is often initially attributed to diarrhea.

Management

Electrolyte and bicarbonate repletion, hydration, and hold/discontinue for significant tubulopathy; tubular abnormalities may resolve over months. Supportive care; nephrology input for persistent Fanconi physiology.Lesion-level management framework

Risk factors

Concurrent GI toxicity/dehydration
Pre-existing CKD
Concurrent nephrotoxins

Prevention

Maintain hydration and manage diarrhea

Anticancer mechanism· how it treats cancer

Antibody-drug conjugate targeting HER2 and delivering deruxtecan (DXd), a topoisomerase I inhibitor, via a cleavable tetrapeptide linker with a high drug-to-antibody ratio (~8) and a membrane-permeable payload that produces a bystander effect on neighboring cells. Approved (including tumor-agnostic) for HER2-positive/HER2-low breast, gastric and other solid tumors.

§04

Clinical depth

Renal dose adjustment

No starting-dose adjustment for mild (CLcr 60 to <90) or moderate (CLcr 30 to <60) renal impairment; however, a higher incidence of grade 1-2 ILD/pneumonitis has been observed in moderate impairment, so monitor those patients more frequently. The recommended dosage has not been established for severe impairment (CLcr <30). The cytotoxic DXd is hepatically metabolized (CYP3A4).

Dialyzability & ESKD dosing

Intact ADC and protein-bound DXd are not appreciably dialyzed. No supplemental dosing guidance established for HD/PD.

Differential diagnosis

Separate Fanconi-pattern tubulopathy (normoglycemic glucosuria, phosphaturia, non-gap acidosis) from prerenal AKI of diarrhea (volume-responsive, no glucosuria) and from myeloma/light-chain tubulopathy if comorbid. Tubular wasting out of proportion to volume status should prompt urine electrolyte studies.

Monitoring

Serum electrolytes (K, phosphate, magnesium, bicarbonate) and creatinine each cycle
Urinalysis for glucosuria/proteinuria if tubular wasting is suspected
Pulmonary symptoms/imaging for interstitial lung disease (the dominant labeled organ toxicity)

Key trials & series

DESTINY-Breast03/04 program (registrational efficacy/safety)
Kalantri Cureus 2023 (reversible Fanconi syndrome case)

Clinical pearls

Think Fanconi, not just dehydration, when a T-DXd patient has refractory hypokalemia/hypophosphatemia with normoglycemic glucosuria.
The membrane-permeable bystander payload that makes T-DXd effective is the same property invoked for off-target proximal tubular injury.
The headline T-DXd toxicity remains interstitial lung disease/pneumonitis — the renal signal is genuinely thin and case-level.

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

Class-level context for the major non-renal toxicities of the Antibody-drug conjugate (HER2/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

5 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

5 references · 2017–2026 · 3 since 2024

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 · LimitedComplete response to trastuzumab-deruxtecan (Enhertu, T-DXd) in HER2-positive stage IVB uterine carcinosarcoma.Kim M et al. · Gynecol Oncol Rep 2025 · PMID 40687920Patient on prolonged trastuzumab deruxtecan therapy developed a reversible acute kidney injury that resolved without sequelae, documenting renal toxicity of the drug.

FDA label — boxed warning & renal dosing· boxed warning · renal impairment

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

Boxed warning

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and the need to immediately report symptoms [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] . Embryo-Fetal Toxicity: Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ] . WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Interstitial lung disease (ILD) and pneumonitis, including severe, life threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. ( 2.3 , 5.1 ) Exposure to ENHERTU during…

Renal impairment — from the label

No dose adjustment of ENHERTU is recommended in patients with mild (creatinine clearance [CLcr] 60 to <90 mL/min) or moderate (CLcr 30 to <60 mL/min) renal impairment [see Clinical Pharmacology (12.3) ] . A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment [see Warnings and Precautions (5.1) ]. Monitor patients with moderate renal impairment more frequently. The recommended dosage of ENHERTU has not been established for patients with severe renal impairment (CLcr <30 mL/min) [see Clinical Pharmacology (12.3) ].

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 10,021 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

Electrolyte Disturbancecorroborated · ROR 1.81 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
Acute Tubular NecrosisNot measurable in reporting — Reporters cannot reliably name this lesion, so its absence from FAERS is expected and is not evidence against the documented injury.
Fanconi SyndromeNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.

SIADH / Hyponatremia

ROR 1.9095% CI 1.51–2.40· 73 reports

Electrolyte Disturbance

ROR 1.8195% CI 1.55–2.11· 164 reports

FAERS outcomes & reporting trend· 25.7% of reports w/ death · 24.3% w/ hospitalization

25.7%

Reported with a death outcome

2,575 of 10,021 reports

24.3%

Reported with hospitalization

2,439 of 10,021 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 10,021 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 0.7095% CI 0.53–0.92· 51 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

Gastrointestinal

Nausea1,219Diarrhoea575Vomiting560Constipation243

General / constitutional

Fatigue797Asthenia381Weight Decreased257Malaise247Pyrexia187

Respiratory

Interstitial Lung Disease1,020Pneumonitis401Dyspnoea321

Blood & lymphatic

Neutropenia251Myelosuppression234Anaemia221Platelet Count Decreased195Neutrophil Count Decreased186

Metabolic & electrolyte

Decreased Appetite382

Skin

Alopecia347

Immune / infection

Pneumonia246

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 Trastuzumab deruxtecan 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

Imatinib

Gleevec · BCR-ABL TKI

Profile

Fluid retention; rare Fanconi and AKI.

LYTEFANCATN

Mild#1 · 84% phenotype match

Streptozocin

Zanosar · Nitrosourea alkylator

Profile

Classic proximal tubular toxin → Fanconi and dose-limiting AKI.

FANCATNLYTE

Severe#2 · 84% 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 · 81% phenotype match

Azacitidine

Vidaza · Hypomethylating agent

Profile

Proximal (type 2) RTA / Fanconi-like tubulopathy; overt AKI uncommon.

FANCATNLYTE

Moderate#4 · 77% phenotype match

Enfortumab vedotin

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

Profile

Emerging AKI and electrolyte signals in urothelial cancer.

ATNLYTEPRE

Moderate#5 · 76% phenotype match

Nedaplatin

Aqupla · Platinum agent

Profile

Second-gen platinum with reduced renal toxicity vs cisplatin.

ATNLYTE

Moderate#6 · 73% phenotype match

Compare Trastuzumab deruxtecan 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.