Is kidney injury from Trastuzumab emtansine (T-DM1) reversible?

Variable. Typical onset: Variable; reported after initiation, over weeks to months of therapy..

How should kidney function be monitored during Trastuzumab emtansine (T-DM1) therapy?

Platelet count and LFTs each cycle (dominant labeled toxicities; thrombocytopenia can accompany TMA); Serum creatinine and urine protein periodically; Hemolysis labs (LDH, haptoglobin, schistocytes) if cytopenias plus AKI raise suspicion for TMA.

Who is at higher risk of kidney injury from Trastuzumab emtansine (T-DM1)?

Pre-existing CKD or glomerular disease; Concurrent nephrotoxins; Treatment-emergent thrombocytopenia.

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Printable monograph

Antibody-drug conjugate (HER2/DM1)

Trastuzumab emtansine (T-DM1)

Kadcyla · T-DM1

Antibody-drug conjugate (HER2/DM1) · approved 2013 · 7 citations

Up to date· through 2026

Fairly sourced6/9 · 5 signals

Met: 7 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 11y)
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/DM1 conjugate with rare vascular-pattern renal injury — case reports of TMA and collapsing glomerulopathy.

ModerateAntibody-drug conjugate

HER2-positive breast cancer

§01

Signature kidney injury

Signature lesion

Thrombotic Microangiopathy

Renal toxicity is rare and case-level. FDA adverse-event analyses flagged renal events with trastuzumab-based therapy, and biopsy-proven cases (collapsing focal segmental glomerulosclerosis; TMA-like microvascular injury) have been reported. Incidence is not quantified.Source: Hakroush et al., Front Oncol 2021 (case)

Onset & rechallenge

Time to injuryVariable / unpredictable

Reported after initiation, over weeks to months of therapy.

Distilled from: “Variable; reported after initiation, over weeks to months of therapy.”

§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.

Thrombotic Microangiopathy#1 · Signaturequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.
Glomerular Injury / ProteinuriaRareno population incidence denominator
Collapsing FSGS with nephrotic-range proteinuria and tubular injury, biopsy-proven — case report PMID 34912725 (opens PubMed in a new tab)
HypertensionRarequalitative — no citable incidence
Grade >=3 systemic hypertension elevated in RCT meta-analysis (RR 1.59).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityVariable

Evidence7 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / EndotheliumGlomerular & peritubular capillaries

Thrombotic Microangiopathy

Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

§03

Kidney injury

Mechanism of kidney injury

Anti-HER2 therapy can perturb glomerular endothelial/podocyte homeostasis (HER2 and VEGF-related signaling), producing rare thrombotic microangiopathy with microvascular thrombosis or a collapsing glomerulopathy with podocyte injury on biopsy. Thrombocytopenia and hepatic (nodular regenerative hyperplasia) changes are recognized class effects of DM1-based therapy; the renal mechanism remains case-level and incompletely defined.

Clinical presentation

Proteinuria (sometimes nephrotic-range), AKI, and — with TMA — microangiopathic hemolytic anemia (schistocytes, elevated LDH, low haptoglobin) with thrombocytopenia; biopsy may show collapsing FSGS or microangiopathic vascular injury.

Management

Hold/discontinue for significant renal injury; supportive care, manage TMA per cause (stop the offending agent; plasma exchange/complement inhibition have been used in proteasome-inhibitor TMA but evidence in ADC-TMA is anecdotal); nephrology evaluation and kidney biopsy for unexplained proteinuria or AKI.Lesion-level management framework

Risk factors

Pre-existing CKD or glomerular disease
Concurrent nephrotoxins
Treatment-emergent thrombocytopenia

Anticancer mechanism· how it treats cancer

Antibody-drug conjugate linking trastuzumab to the maytansinoid microtubule inhibitor DM1 (emtansine) via a non-cleavable thioether linker. Approved for HER2-positive breast cancer, including adjuvant therapy for residual invasive disease after neoadjuvant treatment.

§04

Clinical depth

Renal dose adjustment

No starting-dose adjustment for mild-moderate renal impairment; data are lacking in severe impairment/ESKD. DM1 is hepatically metabolized; thrombocytopenia and hepatotoxicity (not renal clearance) drive most dose modifications.

Dialyzability & ESKD dosing

Not appreciably dialyzed (large ADC; non-cleavable linker, hepatically handled payload).

Differential diagnosis

Distinguish drug-associated TMA (MAHA, thrombocytopenia, schistocytes) from collapsing glomerulopathy (heavy proteinuria, podocyte collapse without systemic MAHA) and from unrelated diabetic/hypertensive glomerular disease. Biopsy is often required to separate these.

Monitoring

Platelet count and LFTs each cycle (dominant labeled toxicities; thrombocytopenia can accompany TMA)
Serum creatinine and urine protein periodically
Hemolysis labs (LDH, haptoglobin, schistocytes) if cytopenias plus AKI raise suspicion for TMA

Key trials & series

EMILIA/KATHERINE registrational program (safety backbone)
Hakroush Front Oncol 2021 (biopsy-proven collapsing FSGS)

Clinical pearls

T-DM1 thrombocytopenia is common and benign in most patients, but cytopenias plus AKI and hemolysis should trigger a TMA workup.
The renal lesions reported are vascular/glomerular (TMA, collapsing FSGS), not tubular — proteinuria, not tubular wasting, is the clue.
Hepatotoxicity and thrombocytopenia, not nephrotoxicity, govern routine dose decisions.
Randomized-trial meta-analysis shows T-DM1 raises grade >=3 systemic hypertension risk (RR 1.59) — distinct from its separately reported pulmonary-arterial and portal hypertension signals.

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

Class-level context for the major non-renal toxicities of the Antibody-drug conjugate (HER2/DM1) 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. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2015–2024 · 3 since 2022

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.

CaseB · ModerateIgA Vasculitis Developing during Trastuzumab Emtansine Therapy for HER2-positive Breast Cancer.Watanabe N et al. · Intern Med 2026 · PMID 41780977Elderly woman on trastuzumab emtansine (T-DM1) developed purpura, hematuria, proteinuria and declining renal function; skin biopsy showed leukocytoclastic vasculitis with IgA deposition and renal biopsy showed proliferative glomerulonephritis with fibrotic crescents, diagnosed as T-DM1-associated IgA vasculitis. Dual biopsy confirmation; nephrology-authored.

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

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

Boxed warning

WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY Hepatotoxicity: Serious hepatotoxicity has been reported, including liver failure and death in patients treated with KADCYLA. Monitor serum transaminases and bilirubin prior to initiation of KADCYLA treatment and prior to each KADCYLA dose. Reduce dose or discontinue KADCYLA as appropriate in cases of increased serum transaminases or total bilirubin. ( 2.3 , 5.1 ) Cardiac Toxicity: KADCYLA administration may lead to reductions in left ventricular ejection fraction (LVEF). Evaluate left ventricular function in all patients prior to and during treatment with KADCYLA. Withhold treatment for clinically significant decrease in left ventricular function. ( 2.3 , 5.2 ) Embryo-Fetal Toxicity: Exposure to KADCYLA during pregnancy can result in embryo-fetal harm. Advise patients of these risks and the need for effective contraception. ( 5.3 , 8.1 , 8.3 ) WARNING: HEPATOTOXICITY, CARDIAC TOXICITY, EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning Hepatotoxicity, liver failure and death have occurred in KADCYLA-treated patients. Monitor hepatic function prior to initiation and prior to each dose. Institute dose modifications or permanently discontinue as appropriate. ( 2.3 , 5.1 ) KADCYLA may lead to reductions in left ventricular ejection fraction (LVEF). Assess LVEF prior to initiation.…

Renal impairment — from the label

No dedicated renal impairment trial for KADCYLA has been conducted. Based on the population pharmacokinetics, as well as analysis of Grade 3 or greater adverse reactions and dose modifications, dose adjustments of KADCYLA are not needed in patients with mild (creatinine clearance [CLcr] 60 to 89 mL/min) or moderate (CLcr 30 to 59 mL/min) renal impairment. No dose adjustment can be recommended for patients with severe renal impairment (CLcr less than 30 mL/min) because of the limited data available [see Clinical Pharmacology (12.3) ] .

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 8,382 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· 3 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

Hypertensioncorroborated · ROR 1.42 — on the terms that name the lesion (ROR 1.43)
Thrombotic MicroangiopathyNo 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.
Glomerular Injury / ProteinuriaNo 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.

Electrolyte Disturbance

ROR 3.6295% CI 3.21–4.09· 270 reports

SIADH / Hyponatremia

ROR 3.2995% CI 2.72–3.99· 105 reports

Hypertension

ROR 1.4295% CI 1.24–1.62· 217 reports

FAERS outcomes & reporting trend· 13.8% of reports w/ death · 25.7% w/ hospitalization

13.8%

Reported with a death outcome

1,156 of 8,382 reports

25.7%

Reported with hospitalization

2,153 of 8,382 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 8,382 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 0.6795% CI 0.49–0.91· 41 AKI reports ·AKI is reported less often than for other drugs (CI entirely below 1) — no disproportionate signal.

General / constitutional

Fatigue757Pyrexia332Weight Decreased317Asthenia301Pain290

Gastrointestinal

Nausea735Diarrhoea598Vomiting349Constipation271

Blood & lymphatic

Thrombocytopenia477Platelet Count Decreased435Anaemia233

Nervous system

Neuropathy Peripheral454Headache433

Respiratory

Dyspnoea299Cough244

Immune / infection

Pneumonia286Nasopharyngitis208

Vascular

Epistaxis320

Skin

Rash230

Metabolic & electrolyte

Decreased Appetite209

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 emtansine (T-DM1) 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

Ziv-aflibercept

Zaltrap · VEGF trap

Profile

Hypertension and proteinuria like bevacizumab.

HTNGLOMTMA

Moderate#1 · 78% phenotype match

Bevacizumab

Avastin · Anti-VEGF antibody

Profile

Proteinuria, hypertension, glomerular TMA.

GLOMHTNTMA

Moderate#2 · 78% phenotype match

Ramucirumab

Cyramza · Anti-VEGFR2 antibody

Profile

Hypertension and proteinuria, class effect.

HTNGLOMTMA

Moderate#3 · 78% phenotype match

VEGFR TKIs (sunitinib · sorafenib · pazopanib · axitinib)

VEGFR TKI

Profile

Hypertension as an on-target marker; proteinuria.

HTNGLOMTMA

Moderate#4 · 78% phenotype match

Pazopanib

Votrient · VEGFR TKI

Profile

VEGFR-TKI; hypertension, proteinuria, TMA.

GLOMHTNTMA

Moderate#5 · 76% phenotype match

Axitinib

Inlyta · VEGFR TKI

Profile

Potent VEGFR-TKI; hypertension and proteinuria dominate.

HTNGLOMTMA

Moderate#6 · 75% phenotype match

Compare Trastuzumab emtansine (T-DM1) 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.