Cetuximab & Panitumumab
Erbitux · Vectibix · Anti-EGFR antibody
TRPM6 magnesium wasting.
LYTE
MildOpen →
Topoisomerase II inhibitor (acridine)
Amsacrine
Amsidine · mAMSA
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 · approved 1987
Refractory or relapsed acute myeloid leukemia (often in salvage/combination regimens)Acute lymphoblastic leukemia (salvage, historical/regional use)
Signature kidney injury
Electrolyte Wasting
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
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.
Onset
TLS within hours to days of effective cytoreduction.
Reversibility
Reversible
Anticancer mechanism
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.
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.
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
- Monitor electrolytes and ECG
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.
Clinical depth
Renal dose adjustment
Pharmacokinetic data support initial dose reduction (on the order of 30-40%) in patients with severe hepatic or renal impairment or with documented impaired drug clearance, since elimination is predominantly hepatobiliary and is prolonged in organ dysfunction.
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
- CBC and urine output
Key trials & series
- Amsacrine pharmacokinetic studies in AML defining predominantly hepatic/biliary elimination and minor renal clearance (PMID 3855288, PMID 6687834)
Clinical pearls
- Amsacrine is cleared mainly by the liver and bile, so renal clearance is minor and the kidney's main exposure to risk is tumor lysis.
- Reduce the dose in severe hepatic or renal impairment because impaired clearance drives the worst toxicity.
- Watch potassium and the QT interval; the headline amsacrine toxicity is cardiac, often electrolyte-related, rather than renal.
Where it strikes
Nephron segments
Tubular Lumen
The urine flow path
Proximal Tubule
Bulk reabsorption + drug uptake (OCT2, OATs)
Injury signatures
Electrolyte WastingAcute Tubular Necrosis
Beyond the kidney
Class-level context for the major non-renal toxicities of topoisomerase ii inhibitor (acridine)s.
Neurologic
Neuropathy, encephalopathy, ICANS, PRES
- Peripheral neuropathy (taxanes, vinca)
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression
Immune / Infusion
CRS, infusion reactions, irAEs, anaphylaxis
- Hypersensitivity (taxane vehicles)
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
PMIDPharmacokinetics 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.PMIDHuman 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.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.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.