Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Anthracycline
Idarubicin
Idamycin · IDAR
An anthracycline for AML whose AKI is the leukemia's tumor lysis, not the drug's tubular toxicity.
MildAnthracycline · approved 1990
Acute myeloid leukemia (in combination with cytarabine)
Signature kidney injury
Prerenal / Hemodynamic AKI
Minimal intrinsic nephrotoxicity; the dominant renal threat is tumor lysis syndrome in acute leukemia. In one inv(16) AML induction cohort tumor-lysis AKI occurred in ~6%, with some requiring hemodialysis; a general drug-specific AKI rate is not quantified.
Source: Burnett et al., J Clin Oncol 2013
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityMild
ReversibilityReversible
Evidence0 refs
Nephron map
Vasculature / EndotheliumGlomerular & peritubular capillaries
Distal Tubule / Collecting Duct
Tubular Lumen
Prerenal / Hemodynamic AKI
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Mechanism of kidney injury
Minimal intrinsic nephrotoxicity; the renal injury is tumor lysis during induction. Rapid blast lysis floods the circulation with potassium, phosphate and purines, producing uric-acid and calcium-phosphate crystal nephropathy in the distal nephron with intratubular obstruction and AKI. Leukostasis/high WBC and concomitant sepsis/nephrotoxins compound the injury.
Clinical presentation
Tumor lysis within 12-72 h of induction: hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia, a high LDH and oliguric AKI. Certain cytogenetics (e.g. inv(16)) are flagged as high-risk for fulminant tumor lysis in AML.
Onset
Hours to days after starting induction.
Reversibility
Reversible
Anticancer mechanism
Anthracycline that intercalates DNA and inhibits topoisomerase II, producing double-strand breaks; high lipophilicity (4-demethoxy) gives strong cellular uptake, and the long-lived active metabolite idarubicinol contributes to efficacy.
Management
Aggressive hydration, rasburicase, electrolyte management, and renal replacement therapy if refractory. Support cytopenias and treat concomitant sepsis.
Risk factors
- High WBC/blast count and high LDH
- Elevated baseline creatinine or uric acid
- Bulky disease and proliferative/inv(16) AML
- Volume depletion
Prevention
- Hydration plus allopurinol (intermediate) or rasburicase (high-risk) before cytoreduction
- Leukapheresis for hyperleukocytosis
- Avoid urinary alkalinization
Note · Established (1990) anthracycline; renal events are tumor-lysis-driven in acute leukemia and not population-quantified.
Clinical depth
Renal dose adjustment
Primarily hepatobiliary elimination; reduce in hepatic dysfunction. The manufacturer advises caution/consideration of reduction in renal impairment (e.g. serum creatinine >2 mg/dL) but provides no precise CrCl algorithm; cumulative anthracycline cardiotoxicity limits dosing.
Dialyzability & ESKD dosing
Not appreciably dialyzable (large volume of distribution and tissue binding); dialysis manages tumor-lysis derangements.
Differential diagnosis
Tumor lysis versus sepsis-associated AKI versus nephrotoxic antimicrobials versus leukemic renal infiltration versus contrast.
Monitoring
- Tumor-lysis panel every 6-12 h during induction
- CBC, LDH and renal function
- Cardiac LVEF (cumulative anthracycline dose)
Key trials & series
- AML15 (Burnett, J Clin Oncol 2013) — FLAG-Ida induction in AML
- QuANTUM-First (Erba, Lancet 2023) — idarubicin within the 7+3 backbone
Clinical pearls
- Idarubicin AKI is the leukemia's tumor lysis, not the drug's tubular toxicity.
- inv(16) AML is a recognized high-risk subgroup for fulminant tumor lysis.
- Hepatobiliary clearance means hepatic, not renal, dose-cuts dominate.
- Cardiotoxicity remains the long-term dose-limiting toxicity.
Where it strikes
Nephron segments
Tubular Lumen
The urine flow path
Distal Tubule / Collecting Duct
Fine-tuning of Na, K, Mg, acid & water
Injury signatures
Crystal / Obstructive NephropathyElectrolyte WastingPrerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of anthracyclines.
Cardiac
Cardiomyopathy, QT, ischemia, myocarditis
- Dose-dependent cardiomyopathy and heart failure
Hematologic
Cytopenias, thrombosis, TMA
- Myelosuppression
Evidence
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkOptimization 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; FLAG-Ida (idarubicin) induction shown effective.PMIDQuizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): a randomised, double-blind, placebo-controlled, phase 3 trial.Erba HP et al. · Lancet 2023 · PMID 37116523Contemporary phase 3 AML trial using idarubicin within the 7+3 induction backbone.PMIDAcute myeloid leukemia induction with cladribine: Outcomes by age and leukemia risk.Schoen MW et al. · Leuk Res 2018 · PMID 29574395Idarubicin-cytarabine-cladribine (IAC) AML induction outcomes.PMIDFulminant tumour lysis syndrome in acute myelogenous leukaemia with inv(16)(p13;q22).Seftel MD et al. · Eur J Haematol 2002 · PMID 12431237Tumor-lysis/AKI in AML induction with inv(16) high-risk and hemodialysis needs.PMIDThe tumor lysis syndrome.Howard SC et al. · N Engl J Med 2011 · PMID 21561350Pathophysiology/management of tumor-lysis crystal nephropathy.PMIDGuidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review.Coiffier B et al. · J Clin Oncol 2008 · PMID 18509186Tumor-lysis prophylaxis/treatment guideline (rasburicase, hydration).
Related agents
Other agents sharing the same signature kidney injury.