How should kidney function be monitored during Arsenic trioxide therapy?

ECG/QTc at baseline and serially; keep QTc <500 ms; Potassium and magnesium frequently (replete to high-normal); Differentiation-syndrome assessment (weight, oxygenation, symptoms) during induction; Serum creatinine and tumor-lysis labs.

How can kidney injury from Arsenic trioxide be prevented?

Early/prophylactic corticosteroids for differentiation syndrome Maintain potassium >4 mEq/L and magnesium >1.8 mg/dL; serial ECG/QTc monitoring Hydration and TLS prophylaxis Avoid additive QT-prolonging agents

Who is at higher risk of kidney injury from Arsenic trioxide?

Hyperleukocytosis; Concurrent QT-prolonging drugs or baseline electrolyte abnormalities; Bulky disease; Volume depletion; Renal impairment (reduced arsenic clearance).

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Printable monograph

Differentiating agent

Arsenic trioxide

Trisenox · ATO

Differentiating agent · approved 2000 · 9 citations · FAERS AKI reporting ROR 2.02 (95% CI 1.56–2.62, 58 AKI reports)

Up to date· through 2025

Deeply sourced8/9 · 7 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 14y)
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.

Ancient poison turned APL cure — its differentiation syndrome (plus QT and electrolyte risk) is what threatens the kidneys.

ModerateDifferentiating agent

Acute promyelocytic leukemia (APL)

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Differentiation syndrome (the main route to AKI) occurs in a substantial minority of APL patients; grade 3–4 renal toxicity in ATO-based regimens is uncommon in randomized data. Direct nephrotoxicity is not well quantified, but QT prolongation and electrolyte disturbances are frequent and clinically important.Source: Sasijareonrat et al., Technol Cancer Res Treat 2020

Onset & rechallenge

Time to injurySubacute (~1–6 weeks)

Differentiation syndrome within the first weeks of induction.

Distilled from: “Differentiation syndrome within the first weeks of induction; QT/electrolyte effects throughout treatment.”

§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.

Prerenal / Hemodynamic AKI#1 · Signature20%PMID 32215187 (opens PubMed in a new tab)
Differentiation syndrome develops in ~20-25% of APL patients treated with differentiating agents (arsenic trioxide / ATRA), driving capillary leak and hemodynamic/renal compromise.
Acute Tubular NecrosisSecondaryqualitative — 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).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityReversible

Evidence9 citations

Nephron map

Vasculature / Endothelium

Proximal Tubule

Distal Tubule / Collecting Duct

Prerenal / Hemodynamic AKI

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

§03

Kidney injury

Mechanism of kidney injury

As with ATRA, blast differentiation triggers a cytokine-mediated capillary-leak/differentiation syndrome with hypotension and fluid shifts causing prerenal AKI (and potential ischemic ATN). Arsenic is predominantly renally excreted and prolongs the QT interval; it causes hypokalemia/hypomagnesemia that must be corrected to prevent torsades. Renal impairment reduces arsenic clearance, raising exposure and cardiac/electrolyte risk.

Clinical presentation

Differentiation syndrome (dyspnea, infiltrates, edema, hypotension, acute renal failure); QT prolongation; hypokalemia/hypomagnesemia requiring electrolyte correction. Leukocytosis during induction is common.

Management

Dexamethasone for differentiation syndrome; supportive hemodynamics, aggressive electrolyte repletion and QT monitoring; hold ATO for severe differentiation syndrome or marked QTc prolongation.Lesion-level management framework

Risk factors

Hyperleukocytosis
Concurrent QT-prolonging drugs or baseline electrolyte abnormalities
Bulky disease
Volume depletion
Renal impairment (reduced arsenic clearance)

Prevention

Early/prophylactic corticosteroids for differentiation syndrome
Maintain potassium >4 mEq/L and magnesium >1.8 mg/dL; serial ECG/QTc monitoring
Hydration and TLS prophylaxis
Avoid additive QT-prolonging agents

Anticancer mechanism· how it treats cancer

Arsenic trioxide binds cysteine residues of the PML moiety of the PML-RARA fusion, triggering its SUMOylation and proteasomal degradation; it induces both differentiation (low dose) and apoptosis (high dose) of promyelocytic blasts, curing the majority of APL when combined with ATRA.

Note · Renal injury is chiefly a differentiation-syndrome/hemodynamic phenomenon; cardiac (QT) and electrolyte management are integral and become more critical when renal clearance of arsenic falls.

§04

Clinical depth

Renal dose adjustment

No formal CrCl-based dose schedule is established, but because arsenic is largely renally excreted, dose reduction and intensified monitoring are advised in significant renal impairment; the label notes caution and reduced clearance in renal dysfunction. Standard induction is 0.15 mg/kg/day.

Dialyzability & ESKD dosing

Arsenic is partially dialyzable, and case experience supports continuing arsenic trioxide with dosing around hemodialysis sessions in ESKD; given renal excretion, careful exposure/QT monitoring is essential.

Differential diagnosis

Differentiation syndrome (capillary leak, renal failure) vs sepsis vs fluid overload; arsenic-related electrolyte/QT effects vs other QT-prolonging drugs. Separate prerenal/differentiation AKI from tumor lysis by the metabolic profile.

Monitoring

ECG/QTc at baseline and serially; keep QTc <500 ms
Potassium and magnesium frequently (replete to high-normal)
Differentiation-syndrome assessment (weight, oxygenation, symptoms) during induction
Serum creatinine and tumor-lysis labs

Key trials & series

Lo-Coco et al., NEJM 2013 — APL0406 (ATRA + arsenic trioxide registrational chemo-free regimen)
Sasijareonrat et al., Technol Cancer Res Treat 2020 — meta-analysis of differentiation syndrome and renal/cardiac toxicity

Clinical pearls

Unlike most agents here, arsenic is renally excreted and partly dialyzable — renal impairment raises exposure and QT/electrolyte risk.
Aggressively keep potassium and magnesium high-normal and watch the QTc to prevent torsades.
Differentiation syndrome (with renal failure) is the shared ATRA/ATO toxicity — treat early with steroids.

Beyond the kidney — non-renal toxicities· 2 organ systems

Class-level context for the major non-renal toxicities of the Differentiating agent class.

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Differentiation syndrome

Cardiac

Cardiomyopathy, QT, ischemia, myocarditis

QT prolongation

§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 · 2013–2025 · 2 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· 3

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 · Limited[Acute kidney failure in differentiation syndrome: a possible complication during therapy with differentiating agents for acute promyelocytic leukemia. A case report].Di Micco L et al. · G Ital Nefrol 2019 · PMID 31373469Young APL patient developed severe acute kidney failure requiring hemodialysis as part of differentiation syndrome (hypotension, capillary leak, edema) after ATRA/ATO induction, illustrating hemodynamic AKI.CaseC · LimitedArsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report.He H et al. · Front Med 2017 · PMID 2842504268-year-old APL patient on arsenic trioxide developed rhabdomyolysis with acute renal insufficiency and elevated creatinine, a rare direct renal toxicity of ATO.CaseC · LimitedArsenic trioxide for the treatment of a relapsed acute promyelocytic leukemia with acute renal failure.Yoon HS et al. · Pediatr Blood Cancer 2011 · PMID 21656902Adolescent with relapsed APL treated with arsenic trioxide developed acute renal failure with fatal outcome, documenting renal compromise in the setting of ATO therapy.

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

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

Boxed warning

WARNING: DIFFERENTIATION SYNDROME, CARDIAC CONDUCTION ABNORMALITIES AND ENCEPHALOPATHY INCLUDING WERNICKE'S Differentiation Syndrome: Patients with acute promyelocytic leukemia (APL) treated with arsenic trioxide have experienced differentiation syndrome, which may be life-threatening or fatal. Signs and symptoms may include unexplained fever, dyspnea, hypoxia, acute respiratory distress, pulmonary infiltrates, pleural or pericardial effusions, weight gain, peripheral edema, hypotension, renal insufficiency, hepatopathy, and multi-organ dysfunction, in the presence or absence of leukocytosis. If differentiation syndrome is suspected, immediately initiate high-dose corticosteroids and hemodynamic monitoring until resolution. Temporarily withhold arsenic trioxide [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ]. Cardiac Conduction Abnormalities: Arsenic trioxide can cause QTc interval prolongation, complete atrioventricular block and torsade de pointes, which can be fatal. Before administering arsenic trioxide, assess the QTc interval, correct electrolyte abnormalities, and consider discontinuing drugs known to prolong QTc interval. Do not administer arsenic trioxide to patients with a ventricular arrhythmia or prolonged QTc interval. Withhold arsenic trioxide until resolution and resume at reduced dose for QTc prolongation [see Dosage and Administration…

Renal impairment — from the label

Monitor patients with severe renal impairment (creatinine clearance less than 30 mL/min) for toxicity when treated with arsenic trioxide; dose reduction may be warranted. ( 8.6 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 3,983 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

Electrolyte Disturbancecorroborated · ROR 1.8 — on the terms that name the lesion (ROR 4.19)
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
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.

Acute Interstitial Nephritis

ROR 2.2595% CI 1.13–4.51· 8 reports

Electrolyte Disturbance

ROR 1.8095% CI 1.41–2.31· 65 reports

Hypertension

ROR 1.5695% CI 1.29–1.88· 113 reports

FAERS outcomes & reporting trend· 6.6% of reports w/ death · 25.3% w/ hospitalization

6.6%

Reported with a death outcome

261 of 3,983 reports

25.3%

Reported with hospitalization

1,006 of 3,983 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 9 systems · 3,983 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 2.0295% CI 1.56–2.62· 58 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

General / constitutional

Fatigue269Pain207Asthenia140Malaise130Pyrexia126

Gastrointestinal

Nausea238Diarrhoea213Vomiting139

Nervous system

Headache217Dizziness179

Musculoskeletal

Arthralgia165Pain In Extremity146Myalgia83

Respiratory

Dyspnoea173Cough121

Skin

Pruritus115Rash114

Psychiatric

Insomnia109Anxiety104

Cardiac

Electrocardiogram Qt Prolonged115

Immune / infection

Pneumonia110

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 Arsenic trioxide 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

Enasidenib

Idhifa · IDH2 inhibitor

Profile

Differentiation syndrome and tumor lysis.

PREATNLYTE

Moderate#1 · 100% phenotype match

Ivosidenib

Tibsovo · IDH1 inhibitor

Profile

Differentiation syndrome → AKI; tumor lysis.

PRELYTEATN

Moderate#2 · 100% phenotype match

Gallium nitrate

Ganite · Antineoplastic metal salt

Profile

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

ATNPRELYTE

Moderate#3 · 88% phenotype match

Lifileucel

Amtagvi · Tumor-infiltrating lymphocyte (TIL) therapy

Profile

2024 cellular therapy; high-dose IL-2 conditioning → capillary leak AKI.

PREATNLYTE

Moderate#4 · 85% phenotype match

Tretinoin (ATRA)

Vesanoid · Retinoid (differentiating agent)

Profile

Differentiation syndrome → capillary leak and AKI.

PREATN

Moderate#5 · 84% phenotype match

Tagraxofusp

Elzonris · IL-3 immunotoxin

Profile

Capillary-leak syndrome → AKI.

PREATN

Moderate#6 · 84% phenotype match

Compare Arsenic trioxide 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.

Who studies this

The leading contributors to Arsenic trioxide’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Arsenic trioxide; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 32 clinical records among all 63 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.