How should kidney function be monitored during Enfortumab vedotin therapy?

Blood glucose before each dose and during treatment (DKA risk); Skin exam and neurologic exam (dominant labeled toxicities) alongside renal review; Serum creatinine and electrolytes each cycle.

How can kidney injury from Enfortumab vedotin be prevented?

Baseline glucose screening and diabetes optimization before the first dose Maintain hydration and manage GI toxicity promptly

Who is at higher risk of kidney injury from Enfortumab vedotin?

Volume depletion from diarrhea/nausea; Hyperglycemia, pre-existing diabetes or elevated BMI; Pre-existing CKD; Concurrent nephrotoxins.

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Printable monograph

Antibody-drug conjugate (Nectin-4/MMAE)

Enfortumab vedotin

Padcev · EV

Antibody-drug conjugate (Nectin-4/MMAE) · approved 2019 · 10 citations · FAERS AKI reporting ROR 3.02 (95% CI 2.58–3.54, 156 AKI reports)

Up to date· through 2025

Fairly sourced6/9 · 6 signals

Met: 10 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 5y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Met: Current through 2025
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 Nectin-4/MMAE conjugate for bladder cancer — usable in renal impairment, with a hyperglycemia-AKI spectrum and case-level tubular injury.

ModerateAntibody-drug conjugate

Urothelial carcinomaBladder cancer

§01

Signature kidney injury

Signature lesion

Acute Tubular Necrosis

Renal injury is not a prominent or well-quantified trial signal, and EV is usable across the spectrum of renal function (including eGFR <30). When AKI occurs it spans prerenal (GI-toxicity dehydration), hyperglycemia/DKA-associated, and case-level tubular (ATN) patterns. In EV-201 cohort 2, three of 89 patients had treatment-related deaths within 30 days (one each from AKI, metabolic acidosis and multi-organ dysfunction), underscoring a real but uncommon acute renal-metabolic risk.Source: Yu et al., Lancet Oncol 2021 (EV-201 cohort 2)

Onset & rechallenge

Time to injuryVariable / unpredictable

Tubular/prerenal AKI tracks intercurrent GI toxicity; hyperglycemic-AKI events often after the second or third dose.

Distilled from: “Variable; tubular/prerenal AKI tracks with intercurrent GI toxicity, and hyperglycemic-AKI events are often reported after the second or third dose.”

§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).
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityVariable

Evidence10 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

MMAE-based ADCs can be taken up off-target by proximal tubular cells and disrupt microtubules, giving a tubular/ATN-pattern picture. Clinically, two added drivers dominate: (1) volume depletion from diarrhea/nausea producing prerenal and ischemic tubular injury, and (2) EV-associated hyperglycemia/diabetic ketoacidosis (a labeled, sometimes fatal effect, disproportionate in patients with elevated BMI) that can drive osmotic diuresis, volume loss and oliguric AKI. The direct human renal mechanism remains incompletely characterized.

Clinical presentation

Often preserved renal function. When AKI occurs: tubular-pattern injury with bland-to-granular sediment, sometimes with electrolyte disturbances; or abrupt hyperglycemia/DKA (severe hyperglycemia, high insulin requirement, ketoacidosis) with oliguric AKI that may require continuous renal replacement therapy. The reported DKA cases progressed rapidly.

Management

Hold for significant AKI or hyperglycemia; rehydrate, correct electrolytes, and treat hyperglycemia/DKA aggressively (insulin, fluids, ICU-level care for ketoacidosis); continuous renal replacement therapy for severe oliguric AKI. The ~3-4 day terminal half-life of EV informs the duration of supportive measures. Resume per tolerance.Lesion-level management framework

Risk factors

Volume depletion from diarrhea/nausea
Hyperglycemia, pre-existing diabetes or elevated BMI
Pre-existing CKD
Concurrent nephrotoxins

Prevention

Baseline glucose screening and diabetes optimization before the first dose
Maintain hydration and manage GI toxicity promptly

Anticancer mechanism· how it treats cancer

Antibody-drug conjugate targeting Nectin-4 and delivering the microtubule inhibitor monomethyl auristatin E (MMAE) via a protease-cleavable linker. Approved for locally advanced/metastatic urothelial carcinoma (as monotherapy and with pembrolizumab).

Note · EV can be given across the spectrum of renal function, including eGFR <30; a direct nephrotoxic signal is emerging and not well quantified. Skin reactions, neuropathy and hyperglycemia dominate the labeled toxicity profile, and the hyperglycemia-AKI axis is the highest-stakes renal-metabolic risk.

§04

Clinical depth

Renal dose adjustment

No starting-dose adjustment for mild-moderate renal impairment; per label, the recommended dose has been administered to patients with CrCl >=15 mL/min, and the drug is used in real-world practice at eGFR <30. Limited data in ESKD/dialysis. The cytotoxic exposure is the released MMAE (hepatically metabolized via CYP3A4), not renally cleared parent ADC.

Dialyzability & ESKD dosing

The intact ADC and protein-bound MMAE are not meaningfully dialyzed; HD is used to support AKI/metabolic complications, not to remove the drug. Terminal half-life ~3.4 days guides how long toxicity (e.g., refractory hyperglycemia) may persist.

Differential diagnosis

Separate prerenal AKI (GI losses, fluid-responsive) from hyperglycemia/DKA-driven AKI (check glucose, ketones, anion gap in every EV patient with new AKI) and from intrinsic MMAE tubular injury (granular casts, persistent after volume repletion).

Monitoring

Blood glucose before each dose and during treatment (DKA risk)
Skin exam and neurologic exam (dominant labeled toxicities) alongside renal review
Serum creatinine and electrolytes each cycle

Key trials & series

EV-301 (Rosenberg, phase III vs chemotherapy)
EV-201 cohort 2 (Yu, Lancet Oncol 2021 — treatment-related AKI/metabolic-acidosis deaths)
UNITE real-world cohort (use at eGFR <30)

Clinical pearls

Always check glucose and ketones when an EV patient presents with AKI — EV-associated DKA can be fulminant and fatal within days, even without known diabetes.
EV is one of the few cytotoxics genuinely usable at eGFR <30, because the active payload is hepatically (not renally) cleared.
Most EV AKI is prerenal/metabolic and reversible; true MMAE tubular injury is a case-level diagnosis.

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

Class-level context for the major non-renal toxicities of the Antibody-drug conjugate (Nectin-4/MMAE) 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

8 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

8 references · 2020–2025 · 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.

Case reports — ranked by strength· 2

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 · LimitedEnfortumab Vedotin-Induced Diabetic Ketoacidosis and Acute Tubulointerstitial Nephritis Requiring Intensive Care in the Treatment of Advanced Urothelial Carcinoma: A Case Report.Matsui R et al. · Case Rep Oncol 2025 · PMID 40487556Patient on enfortumab vedotin developed acute tubulointerstitial nephritis alongside DKA requiring intensive care management.CaseC · LimitedCase report: Enfortumab vedotin induced refractory DKA and multi organ failure - a rare fatal adverse event.Kapoor AK et al. · Front Oncol 2024 · PMID 38425338Enfortumab vedotin-induced refractory DKA with renal failure necessitating continuous renal replacement therapy as part of fatal multi-organ failure.

Conference abstracts & journal reports· 2 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.

AbstractEnfortumab-Vedotin as a Cause of Severe Acute Interstitial NephritisASN Kidney Week 2022 2022 · Abstract SA-PO037Biopsy-proven severe acute interstitial nephritis (creatinine to 6.2 mg/dL) with infusion-tracked rise-and-fall eosinophilia, attributed to the Nectin-4 MMAE antibody-drug conjugate; recovered with steroids and drug discontinuation. Reported as the first AIN case with enfortumab vedotin.AbstractEnfortumab Vedotin-Induced Diabetic Ketoacidosis and AKI: A Case ReportASN Kidney Week 2021 2021 · Abstract PO1883Fatal AKI with granular casts (tubular injury) one week after enfortumab vedotin, alongside diabetic ketoacidosis and toxic epidermal necrolysis; Nectin-4 is expressed on renal tubular epithelium, raising the possibility of direct tubular toxicity beyond the metabolic insult.

FDA label — boxed warning & renal dosing· boxed warning

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

Boxed warning

WARNING: SERIOUS SKIN REACTIONS • PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later. • Closely monitor patients for skin reactions. • Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. • Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.1 )]. WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning. • PADCEV can cause severe and fatal cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). • Immediately withhold PADCEV and consider referral for specialized care for suspected SJS or TEN or severe skin reactions. • Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions. ( 2.2 ), ( 5.1 ), ( 6.1 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 7,224 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· 5 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 2.62 — on the terms that name the lesion (ROR 4.62)
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.
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Acute Interstitial Nephritis

ROR 3.5895% CI 2.37–5.39· 23 reports

Crystal / Obstructive Nephropathy

ROR 3.0495% CI 2.35–3.94· 58 reports

Hemorrhagic Cystitis

ROR 2.7495% CI 2.15–3.50· 65 reports

Electrolyte Disturbance

ROR 2.6295% CI 2.25–3.05· 170 reports

SIADH / Hyponatremia

ROR 2.5895% CI 2.04–3.25· 71 reports

FAERS outcomes & reporting trend· 19.9% of reports w/ death · 33.9% w/ hospitalization

19.9%

Reported with a death outcome

1,434 of 7,224 reports

33.9%

Reported with hospitalization

2,448 of 7,224 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 7,224 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 3.0295% CI 2.58–3.54· 156 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 Injury156

Skin

Rash945Pruritus419Alopecia307Skin Disorder291Stevens-Johnson Syndrome203

General / constitutional

Fatigue404Pyrexia282Asthenia210Malaise207Weight Decreased201

Nervous system

Neuropathy Peripheral852Taste Disorder242

Gastrointestinal

Diarrhoea468Nausea272Vomiting149

Metabolic & electrolyte

Decreased Appetite396Hyperglycaemia254

Blood & lymphatic

Neutropenia170Anaemia153Myelosuppression143

Respiratory

Interstitial Lung Disease190

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 Enfortumab vedotin 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

Gallium nitrate

Ganite · Antineoplastic metal salt

Profile

Dose-limiting acute tubular necrosis; potentiated by dehydration and concurrent nephrotoxins.

ATNPRELYTE

Moderate#1 · 89% 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 · 81% phenotype match

Arsenic trioxide

Trisenox · Differentiating agent

Profile

Differentiation syndrome; QT prolongation.

PREATNLYTE

Moderate#3 · 78% phenotype match

Enasidenib

Idhifa · IDH2 inhibitor

Profile

Differentiation syndrome and tumor lysis.

PREATNLYTE

Moderate#4 · 78% phenotype match

Ivosidenib

Tibsovo · IDH1 inhibitor

Profile

Differentiation syndrome → AKI; tumor lysis.

PRELYTEATN

Moderate#5 · 78% phenotype match

Trastuzumab deruxtecan

Enhertu · Antibody-drug conjugate (HER2/DXd)

Profile

Emerging AKI/proteinuria reports — under-published.

ATNFANCLYTE

Moderate#6 · 76% phenotype match

Compare Enfortumab vedotin 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.