Idarubicin
Idamycin · Anthracycline
Tumor lysis in acute leukemia.
XTALLYTEPRE
Mild#1 · 88% phenotype match
Mitoxantrone
Novantrone · MITO
Anthracenedione · approved 1987 · 9 citations · FAERS AKI reporting ROR 1.46 (95% CI 1.15–1.86, 66 AKI reports)
Dated evidence· through 2016
Deeply sourced7/9 · 6 signals
- Met: 9 citations
- Not met: 12+ references
- Met: Accrued over 10+ years (span: 23y)
- Met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Not met: Current through 2016
- 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 anthracenedione with minimal direct renal toxicity — its kidney risk is tumor lysis, and blue-green urine is benign.
MildAnthracenedione (topoisomerase II inhibitor)
Acute myeloid leukemia (in combination)Hormone-refractory/advanced prostate cancer (with corticosteroids)Secondary-progressive or worsening relapsing-remitting multiple sclerosis
§01
Signature kidney injury
Signature lesion
Direct nephrotoxicity is low and not quantified; the principal renal risk is tumor lysis syndrome when used in bulky/rapidly proliferating hematologic malignancies. Benign blue-green discoloration of urine/sclera is expected (the anthracenedione chromophore), not injury.Source: Tannock et al., NEJM 2004
Onset & rechallenge
Time to injuryAcute (~1–7 days)
Tumor lysis hours to days post-infusion.
Distilled from: “Tumor lysis hours to days post-infusion.”
§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.
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Intravesical instillation only - chemical cystitis in prospective instillation trials.
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence9 citations
Nephron map
Distal Tubule / Collecting Duct
Tubular LumenThe urine flow path
Bladder / Urothelium
Crystal / Obstructive Nephropathy
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
§03
Kidney injury
Mechanism of kidney injury
Low direct nephrotoxicity. The dominant renal mechanism is tumor lysis — massive cell lysis releases purines (uric acid crystal nephropathy in the distal nephron/collecting duct) and phosphate (calcium-phosphate crystal deposition), causing obstructive intratubular crystallopathy and AKI, with hemodynamic/prerenal contributions.
Clinical presentation
When tumor lysis occurs: a rising uric acid, potassium, phosphate and LDH with a falling calcium and oliguric AKI within 12-72 h of dosing. Benign blue-green urine/scleral discoloration is expected and is not a sign of injury.
Management
Aggressive IV hydration, rasburicase for hyperuricemia, electrolyte correction, and renal replacement therapy for refractory metabolic derangement. The blue-green discoloration requires only reassurance.Lesion-level management framework
Risk factors
- High tumor burden/high WBC and high LDH
- Pre-existing renal impairment and volume depletion
- Proliferative AML subtypes
Prevention
- Hydration; allopurinol for intermediate-risk and rasburicase for high-risk tumor lysis
- Avoid urinary alkalinization
- Cap cumulative dose (cardiotoxicity is dose-limiting, ~140 mg/m2 lifetime, lower after prior anthracycline)
Anticancer mechanism· how it treats cancer
Anthracenedione that intercalates DNA and inhibits topoisomerase II, causing DNA strand breaks and impaired replication/repair; it generates fewer free radicals per dose than classic anthracyclines, though cumulative cardiotoxicity remains.
Note · Established (1987) agent; renal events are tumor-lysis-driven and not population-quantified.
§04
Clinical depth
Renal dose adjustment
No well-defined renal CrCl thresholds (minimal renal elimination — predominantly hepatobiliary clearance); reduce/monitor in hepatic impairment. Cumulative dose is limited by cardiotoxicity rather than renal function.
Dialyzability & ESKD dosing
Not appreciably dialyzable (large volume of distribution and high tissue/protein binding); dialysis is used for tumor-lysis metabolic management.
Differential diagnosis
Tumor lysis versus benign anthracenedione pigment (harmless) versus contrast/sepsis AKI versus concomitant nephrotoxins.
Monitoring
- Tumor-lysis labs (uric acid, potassium, phosphate, calcium, LDH), CBC
- Cumulative anthracenedione dose tracking
- LVEF/cardiac monitoring
Key trials & series
- TAX 327 (Tannock, NEJM 2004) — defining mitoxantrone comparator trial in prostate cancer
- AML15 (Burnett, J Clin Oncol 2013) — mitoxantrone in AML consolidation
Clinical pearls
- Direct mitoxantrone nephrotoxicity is minimal — think tumor lysis, not tubular drug toxicity.
- Blue-green urine and scleral discoloration are benign.
- Renal clearance is minor (hepatobiliary), so renal dose-cut thresholds are not well established.
- Cardiotoxicity, not nephrotoxicity, is the dose-limiting organ toxicity.
- Chemical cystitis is an intravesical-route mitoxantrone toxicity in prospective instillation trials; systemic-route hemorrhagic cystitis appears only in cyclophosphamide-based transplant regimens.
§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 · 1993–2016 · 1 since 2014Primary (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.
- 1.LandmarkDocetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.Tannock IF et al. · N Engl J Med · 2004 · PMID 15470213TAX 327 phase 3 — defining mitoxantrone comparator trial in prostate cancer.
- 2.Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial.Burnett AK et al. · J Clin Oncol · 2013 · PMID 23940227Large randomized AML trial using mitoxantrone in consolidation.
- 3.Tumor lysis syndrome following single-dose mitoxantrone.Benekli M et al. · Chemotherapy · 1995 · PMID 8529438Documents mitoxantrone-induced tumor lysis syndrome (single agent).
- 4.Tumor lysis syndrome in the era of novel and targeted agents in patients with hematologic malignancies: a systematic review.Howard SC et al. · Ann Hematol · 2016 · PMID 26758269Systematic tumor-lysis review including mitoxantrone-containing regimens.
- 5.Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review.Coiffier B et al. · J Clin Oncol · 2008 · PMID 18509186Standard tumor-lysis risk-stratification and rasburicase/allopurinol/hydration management.
- 6.The tumor lysis syndrome.Howard SC et al. · N Engl J Med · 2011 · PMID 21561350Authoritative tumor-lysis pathophysiology (uric acid/phosphate crystal nephropathy) and management review.
- 7.Intravesical mitoxantrone in superficial bladder tumours (Ta-T1).Serretta V et al. · Eur J Cancer · 1993 · PMID 8260250Prospective intravesical mitoxantrone study: 25.7% chemical cystitis, 5.7% stopping treatment.
- 8.Intravesical mitozantrone in recurrent superficial bladder cancer: a phase II study.Namasivayam S et al. · Br J Urol · 1995 · PMID 7613831Phase II intravesical mitoxantrone study with withdrawals for chemical cystitis.
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.
FDA label — boxed warning & renal dosing· boxed warning
Quoted verbatim from this agent's current FDA label (Oct 2024) — not paraphrased or interpreted. Full label on DailyMed .
Boxed warning
WARNING Mitoxantrone Injection, USP (concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents. Mitoxantrone Injection, USP (concentrate) should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration (see ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions ). NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration (see WARNINGS, General ). Except for the treatment of acute nonlymphocytic leukemia, mitoxantrone therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm 3 . In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving mitoxantrone. Cardiotoxicity: Congestive heart failure (CHF), potentially fatal, may occur either during therapy with mitoxantrone or months to years after termination of therapy. Cardiotoxicity risk increases with cumulative mitoxantrone dose and may occur whether or not cardiac risk…
What gets reported — FAERS
Everything below is FAERS — adverse events someone chose to report, about 6,238 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
- Hemorrhagic Cystitiscorroborated · ROR 2.64 — on the terms that name the lesion (ROR 29.68)
- Electrolyte Disturbancecorroborated · ROR 1.95 — but the naming terms alone are not disproportionate, so this rests on terms merely consistent with the lesion
- Crystal / Obstructive NephropathyNo 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.
- Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.
Thrombotic Microangiopathy
ROR 3.9295% CI 2.47–6.23· 18 reports
Hemorrhagic Cystitis
ROR 2.6495% CI 2.02–3.44· 54 reports
Electrolyte Disturbance
ROR 1.9595% CI 1.62–2.36· 110 reports
FAERS outcomes & reporting trend· 26.7% of reports w/ death · 35.5% w/ hospitalization
26.7%
Reported with a death outcome
1,663 of 6,238 reports
35.5%
Reported with hospitalization
2,215 of 6,238 reports
Reports per year
- 2015: 210 reports
- 2016: 258 reports
- 2017: 390 reports
- 2018: 616 reports
- 2019: 456 reports
- 2020: 508 reports
- 2021: 356 reports
- 2022: 450 reports
- 2023: 406 reports
- 2024: 309 reports
- 2025: 279 reports
- 2026: 100 reports
Yearly FAERS report volume · most recent year is partial.
FAERS adverse-event signal — all organ systems· 6 systems · 6,238 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 1.4695% CI 1.15–1.86· 66 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.
Blood & lymphatic
Febrile Neutropenia765Neutropenia465Thrombocytopenia345Pancytopenia238Anaemia197
Immune / infection
Sepsis325Pneumonia252Infection199Septic Shock196
Gastrointestinal
Nausea142Diarrhoea140Mucosal Inflammation124Vomiting120
General / constitutional
Pyrexia368Fatigue132
Respiratory
Respiratory Failure167Dyspnoea125
Vascular
Hypotension132
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 Mitoxantrone 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.
Phenotype-similar agents· the numbered markers on the map above
Profile
Dactinomycin (actinomycin D)
Cosmegen · Antitumor antibiotic
Renal risk indirect via tumor lysis in chemosensitive pediatric tumors; hepatic veno-occlusive disease is the signature organ toxicity.
LYTEPREXTAL
Moderate#2 · 73% phenotype match
Etoposide
Etopophos · Topoisomerase II inhibitor
Tumor lysis; renally cleared.
XTALPRELYTE
Mild#3 · 69% phenotype match
Hydroxyurea
Hydrea · Ribonucleotide reductase inhibitor
Tumor lysis in myeloproliferative disease.
XTALPRELYTE
Mild#4 · 69% phenotype match
Nelarabine
Arranon · Purine analog
Tumor lysis in T-ALL.
XTALPRELYTE
Mild#5 · 69% phenotype match
Pomalidomide
Pomalyst · Immunomodulatory drug (IMiD)
Tumor lysis; usable in renal impairment.
PRELYTEXTAL
Mild#6 · 69% phenotype match
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 Antitumor antibiotics
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.
- 1IdarubicinXTAL — Crystal / Obstructive NephropathyMild
- 2BleomycinPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 3DoxorubicinGLOM — Glomerular Injury / ProteinuriaFAERS AKIMild
- 4Mitoxantrone· this agentXTAL — Crystal / Obstructive NephropathyFAERS AKIMild
- 5Plicamycin (mithramycin)ATN — Acute Tubular NecrosisModerate
- 6Dactinomycin (actinomycin D)LYTE — Electrolyte DisturbanceModerate
- 7Mitomycin CTMA — Thrombotic MicroangiopathySevere
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.