What kind of kidney injury does Denileukin diftitox cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Is kidney injury from Denileukin diftitox reversible?

Reversible. Typical onset: Acute, peri-infusion (first 1-2 cycles); generally not cumulative..

How should kidney function be monitored during Denileukin diftitox therapy?

Serum albumin before each cycle (gating parameter); Daily weight and blood pressure during cycles; Edema and infusion-reaction assessment.

How can kidney injury from Denileukin diftitox be prevented?

Optimize serum albumin before each cycle; do not initiate if albumin <3.0 g/dL Premedicate (corticosteroids, antihistamines, antipyretics) Ensure euvolemia/hydration and monitor weight and blood pressure

Who is at higher risk of kidney injury from Denileukin diftitox?

Low baseline serum albumin (key CLS risk — do not initiate if albumin below ~3.0 g/dL); Pre-existing edema or volume overload; Cardiovascular compromise and baseline hypotension.

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Printable monograph

Immunotoxin (IL-2–diphtheria)

Denileukin diftitox

Lymphir · DENI

Immunotoxin (IL-2–diphtheria) · approved 2024 · 8 citations

Up to date· through 2025

Deeply sourced7/9 · 6 signals

Met: 8 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 24y)
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.

An IL-2/diphtheria-toxin fusion whose capillary-leak syndrome drives prerenal AKI — check albumin before every cycle.

ModerateIL-2-diphtheria-toxin immunotoxin

Relapsed or refractory stage I-III cutaneous T-cell lymphoma after at least one prior systemic therapy (improved-purity formulation, denileukin diftitox-cxdl)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Capillary-leak syndrome (CLS) occurred in ~20.3% (grade >=3 ~5.8%) in the 2024 denileukin diftitox-cxdl trial. With the original formulation hypoalbuminemia was very common (~79%, ~15% grade 3/4) and a vascular-leak syndrome occurred in roughly a quarter of patients. AKI here is prerenal/hemodynamic rather than a quantified direct renal injury rate.Source: Foss et al., J Clin Oncol 2024 (20.3% capillary-leak syndrome; attributable AKI rate not separately quantified)

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Acute, peri-infusion over the first one to two cycles (capillary-leak prerenal AKI); generally not cumulative.

Distilled from: “Acute, peri-infusion (first 1-2 cycles); generally not cumulative.”

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Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

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Kidney injury

Mechanism of kidney injury

Capillary/vascular-leak syndrome: IL-2- and toxin-mediated endothelial injury increases vascular permeability, causing fluid and protein extravasation, hypoalbuminemia and intravascular volume depletion, which produces prerenal (hemodynamic) AKI. It is not a direct tubular nephrotoxin.

Clinical presentation

Hypotension, edema, weight gain, hypoalbuminemia and a rising creatinine, often with infusion reactions and transaminase elevation. Onset is within days of infusion, mainly in the first 1-2 cycles.

Management

For CLS: give IV fluids and albumin repletion, hold or discontinue for grade >=3, and provide supportive care for edema. For prerenal AKI: restore volume and perfusion. Most events reverse hemodynamically and are not cumulative.Lesion-level management framework

Risk factors

Low baseline serum albumin (key CLS risk — do not initiate if albumin below ~3.0 g/dL)
Pre-existing edema or volume overload
Cardiovascular compromise and baseline hypotension

Prevention

Optimize serum albumin before each cycle; do not initiate if albumin <3.0 g/dL
Premedicate (corticosteroids, antihistamines, antipyretics)
Ensure euvolemia/hydration and monitor weight and blood pressure

Anticancer mechanism· how it treats cancer

Engineered fusion protein joining interleukin-2 to the catalytic and translocation fragments of diphtheria toxin (DAB389IL-2). IL-2 binds the high-affinity IL-2 receptor (CD25/IL-2R-alpha) on malignant T cells; after internalization the diphtheria-toxin fragment ADP-ribosylates elongation factor 2, halting protein synthesis and causing apoptosis.

Note · Frontier-era 2024 reapproval (improved-purity formulation); the original Ontak was approved in 1999 and withdrawn ~2014 for manufacturing/purity reasons. Renal mechanism is capillary leak / prerenal AKI, well described across formulations.

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Clinical depth

Renal dose adjustment

Weight-based dosing (9 micrograms/kg/day for 5 days every 21 days); modification is driven by toxicity (albumin, organ function), not by CrCl. No CrCl-based dose thresholds are defined.

Dialyzability & ESKD dosing

Not established — a large fusion protein; AKI here is managed hemodynamically rather than by dialytic drug removal.

Differential diagnosis

Distinguish CLS-driven prerenal AKI from sepsis or GI-loss prerenal states, cardiorenal/volume overload, hepatorenal physiology, tumor nephropathy, and infusion-reaction hypotension — versus intrinsic ATN.

Monitoring

Serum albumin before each cycle (gating parameter)
Daily weight and blood pressure during cycles
Edema and infusion-reaction assessment

Key trials & series

Pivotal phase 3 of denileukin diftitox-cxdl (Foss, J Clin Oncol 2024) — CLS ~20.3% (grade >=3 ~5.8%)
Original Ontak pivotal phase 3 (Olsen, J Clin Oncol 2001) — vascular-leak/hypoalbuminemia profile

Clinical pearls

Check albumin before every cycle and do not start if it is below ~3.0 g/dL — the AKI is prerenal, not tubular.
CLS clusters in the first cycles within days of infusion — front-load monitoring.
The improved-purity cxdl (Lymphir) formulation has CLS ~20% (grade >=3 ~6%).
Treat hemodynamically — volume plus albumin reverse most prerenal AKI; injury is generally reversible and non-cumulative.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

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References

7 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

7 references · 2001–2025 · 3 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· 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 · LimitedDenileukin diftitox-induced systemic capillary leak syndrome with acute kidney injury.Horino T et al. · CEN Case Rep 2023 · PMID 35870043Case report of denileukin diftitox-induced systemic capillary leak syndrome causing prerenal/hemodynamic acute kidney injury from plasma extravasation, hypotension, and hypoalbuminemia.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Jan 2025) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: CAPILLARY LEAK SYNDROME Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves, or permanently discontinue based on severity [see Dosage and Administration ( 2.1 , 2.4 ) and Warnings and Precautions ( 5.1 )] . WARNING: CAPILLARY LEAK SYNDROME See full prescribing information for complete boxed warning. Capillary leak syndrome (CLS), including life-threatening or fatal reactions, can occur in patients receiving LYMPHIR. Monitor patients for signs and symptoms of CLS during treatment. Withhold LYMPHIR until CLS resolves or permanently discontinue based on severity. ( 2.1 , 2.4 , 5.1 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 4 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· 1 of 4 reports w/ death · 2 w/ hospitalization

4 reports is below the 50 this atlas requires before quoting a percentage, so the counts are shown instead of shares.

1 of 4

Reported with a death outcome

too few reports to express as a share

2 of 4

Reported with hospitalization

too few reports to express as a share

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 4 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 45.5695% CI 4.74–438.01· 1 AKI reports ·the CI clears 1, but on fewer than 50 reports for this agent in total — too thin a base to call a signal, and the atlas does not count it as one.

Renal & urinary

Acute Kidney Injury1

Respiratory

Hypoxia2Oxygen Saturation Decreased1

Nervous system

Cognitive Disorder1

Vascular

Hypotension1

Skin

Rash1

Immune / infection

Sepsis1

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 Denileukin diftitox 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

Dordaviprone

Modeyso · Imipridone (ONC201; DRD2/ClpP)

Profile

2025 imipridone for H3 K27M glioma; renally well tolerated — QT prolongation, not nephrotoxicity, is the safety focus.

PRE

Mild#1 · 94% phenotype match

Iberdomide

Zenbexus · Cereblon E3 ligase modulator (CELMoD)

Profile

2026 first-in-class CELMoD; no attributable lesion (renal impairment 11% vs 8% on the comparator arm) but exposure rises 1.8x below eGFR 30 off dialysis.

PRE

Mild#2 · 94% phenotype match

Casdatifan

HIF-2α inhibitor (investigational)

Profile

Trial-stage RCC HIF-2α inhibitor; renal profile being defined.

PRE

Mild#3 · 94% phenotype match

Belzutifan

Welireg · HIF-2α inhibitor

Profile

Anemia/hypoxia; emerging renal profile in VHL/RCC.

PRE

Mild#4 · 91% phenotype match

Zolbetuximab

Vyloy · Anti-Claudin-18.2 monoclonal antibody

Profile

2024 gastric mAb; severe on-target nausea/vomiting → volume-depletion prerenal AKI.

PRE

Moderate#5 · 89% phenotype match

Tebentafusp

Kimmtrak · Bispecific T-cell engager (gp100×CD3 ImmTAC)

Profile

CRS-driven hypotension → prerenal AKI early in dosing; uveal melanoma.

PRE

Moderate#6 · 89% phenotype match

Compare Denileukin diftitox 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 Other targeted 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.