Mechlorethamine
Mustargen · Alkylating agent (nitrogen mustard)
Tumor lysis in bulky lymphoma is the main renal hazard; modern topical gel has no detectable systemic absorption.
LYTEXTAL
Moderate#1 · 86% phenotype match
Topoisomerase II inhibitor (acridine)
Amsacrine
Amsidine · mAMSA
Topoisomerase II inhibitor (acridine) · approved 1987 · 4 citations
Dated evidence· through 2017
Fairly sourced5/9 · 4 signals
- Not met: 4 citations
- Not met: 12+ references
- Met: Accrued over 10+ years (span: 34y)
- Met: Beyond single case reports
- Met: High-impact journal
- Met: Landmark reference
- Not met: Current through 2017
- 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.
Acridine topoisomerase II inhibitor for refractory AML; renal clearance is minor and the kidney-relevant risk is tumor lysis, while elimination is chiefly hepatobiliary.
Moderateclassic-cytotoxic
Refractory or relapsed acute myeloid leukemia (often in salvage/combination regimens)Acute lymphoblastic leukemia (salvage, historical/regional use)
§01
Signature kidney injury
Signature lesion
Direct nephrotoxicity is not a prominent feature. The main renal hazard is tumor lysis syndrome during leukemia induction/salvage; incidence specific to amsacrine is not quantified. Pharmacokinetic studies show renal elimination plays only a minor role, with clearance dominated by hepatic metabolism and biliary excretion.Source: Jurlina et al., Cancer Chemother Pharmacol 1985 (renal elimination minor); not quantified
Onset & rechallenge
Time to injuryAcute (~1–7 days)
Tumor lysis within hours to days of effective cytoreduction.
Distilled from: “TLS within hours to days of effective cytoreduction.”
§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.
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
§03
Kidney injury
Mechanism of kidney injury
No well-defined intrinsic tubular toxin at standard exposure. As an active agent against high-turnover leukemia, amsacrine can precipitate tumor lysis with uric-acid/phosphate intratubular precipitation and AKI. Because the drug is highly protein-bound and cleared mainly by hepatic metabolism and biliary excretion, kidney exposure to parent drug is limited; however, severe renal dysfunction prolongs clearance of radiolabeled drug/metabolites and warrants dose reduction.
Clinical presentation
TLS picture (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, rising creatinine) during induction of bulky leukemia. No characteristic amsacrine-specific urinary syndrome. QT prolongation/arrhythmia and hepatotoxicity are the more prominent non-renal toxicities.
Management
Treat TLS with hydration, uric-acid-lowering therapy, electrolyte correction and renal replacement therapy if refractory. Adjust dosing for organ dysfunction. There is no specific renal antidote; supportive care predominates.Lesion-level management framework
Risk factors
- High leukemic burden / high WBC or LDH
- Pre-existing kidney impairment (prolongs clearance)
- Hepatic dysfunction (reduces clearance, increases toxicity)
- Volume depletion and inadequate uric-acid prophylaxis
- Electrolyte abnormalities (hypokalemia) compounding arrhythmia risk
Prevention
- TLS risk stratification and prophylaxis (hydration, allopurinol or rasburicase)
- Correct potassium and magnesium before/during therapy
- Reduce dose in significant hepatic or renal impairment
Anticancer mechanism· how it treats cancer
Aminoacridine derivative that intercalates DNA and inhibits topoisomerase II, stabilizing cleavable complexes and producing protein-associated DNA strand breaks that trigger apoptosis in leukemic cells.
Note · Amsacrine's clinically dominant safety issues are cardiac (QT prolongation, arrhythmia, often hypokalemia-related) and hepatic; renal considerations are secondary and mostly mediated through tumor lysis and altered clearance in organ failure.
§04
Clinical depth
Renal dose adjustment
The pharmacokinetic study recommends an initial dose reduction of 30-40% in severe hepatic or renal impairment or documented impaired drug clearance, since elimination is predominantly hepatobiliary and prolonged in organ dysfunction; compute the absolute dose from the protocol's own baseline rather than a fixed range. Patients with impaired amsacrine clearance experienced the most severe toxicity in that study.
Dialyzability & ESKD dosing
Unlikely to be efficiently dialyzed given very high plasma protein binding (~96-98%) and hepatobiliary elimination; dialysis is reserved for managing TLS metabolic complications rather than drug removal.
Differential diagnosis
Separate TLS-related AKI from prerenal azotemia, sepsis-associated AKI during neutropenia, and nephrotoxicity from co-administered agents. Intrinsic amsacrine tubular injury is not an established entity.
Monitoring
- Serum creatinine, potassium, phosphate, calcium, uric acid during induction
- ECG/QT and electrolytes (especially K and Mg)
- Liver function tests
Key trials & series
- Amsacrine pharmacokinetic studies in AML defining predominantly hepatic/biliary elimination and minor renal clearance (PMID 3855288, PMID 6687834)
Clinical pearls
- Watch potassium and the QT interval; the headline amsacrine toxicity is cardiac, often electrolyte-related, rather than renal.
Where it strikes· nephron segments & injury signatures
Nephron segments
Tubular Lumen
The urine flow path
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Beyond the kidney — non-renal toxicities· 3 organ systems
Class-level context for the major non-renal toxicities of the Topoisomerase II inhibitor (acridine) class.
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (taxanes, vinca)
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression
Immune / Infusion
CRS, infusion reactions, irAEs, anaphylaxis
- Hypersensitivity (taxane vehicles)
§05
References
4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.
Evidence accrual
4 references · 1983–2017 · 1 since 2015Primary (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.Pharmacokinetics of amsacrine in patients receiving combined chemotherapy for treatment of acute myelogenous leukemia.Jurlina JL et al. · Cancer Chemother Pharmacol · 1985 · PMID 3855288Clinical PK study in AML showing urinary excretion of amsacrine is minor and that elimination is susceptible to hepatic, not renal, function.
- 2.Human pharmacokinetics of a new acridine derivative, 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992).Hall SW et al. · Cancer Res · 1983 · PMID 6687834Radiolabeled human PK study establishing hepatic metabolism and biliary excretion as the main elimination routes, with significant renal contribution only in severe kidney dysfunction, supporting dose reduction in organ impairment.
- 3.LandmarkThe tumor lysis syndrome.Howard SC et al. · N Engl J Med · 2011 · PMID 21561350Review of tumor lysis syndrome relevant to leukemia induction with active agents such as amsacrine.
- 4.LandmarkAcute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med · 2017 · PMID 28467867Onconephrology review covering tumor lysis and AKI mechanisms in patients with hematologic malignancy.
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 Amsacrine 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
Infigratinib
Truseltiq · FGFR inhibitor
Hyperphosphatemia — on-target FGFR class effect; nephrocalcinosis risk.
LYTEXTAL
Moderate#2 · 74% phenotype match
Lurbinectedin
Zepzelca · Marine alkylating agent
Rhabdomyolysis risk in small-cell lung cancer.
ATNLYTEXTAL
Mild#3 · 65% phenotype match
Etoposide
Etopophos · Topoisomerase II inhibitor
Tumor lysis; renally cleared.
XTALPRELYTE
Mild#4 · 63% phenotype match
Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
XTALTMALYTE
Moderate#5 · 57% phenotype match
Fludarabine
Fludara · Purine analog
Tumor lysis; accumulates in renal impairment.
XTALPRELYTE
Moderate#6 · 57% 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 Topoisomerase inhibitors
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.
- 1TopotecanPRE — Prerenal / Hemodynamic AKIMild
- 2TeniposideLYTE — Electrolyte DisturbanceMild
- 3IrinotecanPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
- 4EtoposideXTAL — Crystal / Obstructive NephropathyFAERS AKIMild
- 5Amsacrine· this agentLYTE — Electrolyte DisturbanceModerate
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.