Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
FLT3 inhibitor
Quizartinib
Vanflyta · QUIZ
A type II FLT3 inhibitor for AML whose renal risk centers on tumor lysis and electrolyte shifts at induction.
MildFLT3 inhibitor · approved 2023
FLT3-ITD-positive acute myeloid leukemia
Signature kidney injury
Prerenal / Hemodynamic AKI
No established intrinsic nephrotoxicity. In QuANTUM-First the dominant grade 3-4 events were febrile neutropenia, hypokalemia and pneumonia; QT prolongation is a hallmark. Renal injury is indirect — tumor-lysis at induction, sepsis/cytopenia-related prerenal/ischemic AKI, and electrolyte derangements. AKI is common in AML induction generally (KDIGO-defined rates are high in cohort studies), but a quizartinib-attributable rate is not defined.
Source: Erba et al., Lancet 2023
Mechanism of kidney injury
No characterized direct nephron injury. AML induction with quizartinib carries tumor-lysis-type metabolic risk (hyperuricemia/hyperphosphatemia with intratubular urate/calcium-phosphate deposition) and high rates of febrile neutropenia/sepsis driving prerenal and ischemic (ATN) AKI; electrolyte wasting (notably hypokalemia and hypomagnesemia) is common and dangerously interacts with the drug's QT-prolonging effect.
Clinical presentation
AKI in the setting of sepsis/volume depletion or tumor lysis; hypokalemia/hypomagnesemia and other electrolyte derangements; creatinine rise tracking these processes rather than a bland primary tubulopathy.
Onset
Highest around induction (tumor lysis, neutropenic sepsis); ongoing electrolyte monitoring through therapy.
Reversibility
Reversible
Anticancer mechanism
Oral, highly selective type II FLT3 inhibitor (binds the inactive kinase conformation, targeting FLT3-ITD). Added to standard induction/consolidation chemotherapy and given as continuation monotherapy for FLT3-ITD-positive newly diagnosed AML.
Management
Supportive; standard tumor-lysis treatment, sepsis/source control, correction of prerenal factors and electrolytes (K and Mg, partly for arrhythmia prevention). No drug-specific renal therapy; intrinsic nephrotoxicity has not been established.
Risk factors
- High leukemic burden at induction (TLS risk)
- Febrile neutropenia/sepsis
- Electrolyte derangements compounding QT risk
- Concurrent nephrotoxins (antimicrobials, azoles, contrast)
Prevention
- Tumor-lysis prophylaxis (IV hydration, allopurinol/rasburicase) at induction
- Vigilant electrolyte monitoring/repletion (especially potassium and magnesium, also for QT safety)
- Prompt management of neutropenic sepsis and source control
Note · 2023 approval; no renal-specific literature. The prerenal/TLS/electrolyte framing is conservative AML-induction class reasoning, supported by the pivotal trial's toxicity profile and AML-AKI cohort data.
Clinical depth
Renal dose adjustment
No renal dose adjustment is specified for mild-moderate impairment; quizartinib is hepatically (CYP3A) metabolized. Note the critical CYP3A drug-interaction caveat: strong CYP3A inhibitors (common azole antifungals in neutropenia) raise exposure and require dose reduction, mainly for QT safety. Limited data in severe impairment/dialysis.
Dialyzability & ESKD dosing
Not characterized; highly protein-bound, hepatically cleared — not expected to be meaningfully dialyzed. No ESKD dosing guidance.
Differential diagnosis
Distinguish tumor-lysis AKI (early, urate/phosphate), neutropenic-sepsis ATN, and prerenal AKI of volume depletion; the drug is not a direct tubular toxin but its electrolyte effects amplify QT/arrhythmia risk.
Monitoring
- Frequent electrolytes — K, Mg, phosphate, uric acid (TLS and QT safety)
- ECG/QTc at baseline and during therapy (correct K/Mg before/with dosing)
- Creatinine and volume status through neutropenic period
Key trials & series
- QuANTUM-First (Erba, Lancet 2023) — registrational phase 3; febrile-neutropenia/hypokalemia/QT-dominant safety
Clinical pearls
- Replete K and Mg aggressively — both for the kidney/TLS picture AND to mitigate quizartinib's QT prolongation.
- Beware azole antifungal co-administration: CYP3A inhibition raises exposure and QT risk in exactly the febrile-neutropenic patients most likely to need them.
- Renal injury at induction is TLS- and sepsis-driven, not a quizartinib tubulopathy.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKIElectrolyte Wasting
Evidence
4 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkQuizartinib 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 37116523Pivotal trial; toxicity profile (febrile neutropenia, hypokalemia, QT) underpins the indirect renal/electrolyte framing.PMIDAcute Kidney Injury in Patients With Cancer: A Review of Onconephrology.Gudsoorkar P et al. · Adv Chronic Kidney Dis 2021 · PMID 35190106Onconephrology review of tumor-lysis and sepsis-related AKI relevant to AML induction.PMIDTumor Lysis Syndrome.Barbar T et al. · Adv Chronic Kidney Dis 2021 · PMID 35190110Focused TLS review (hydration, rasburicase/allopurinol) underpinning induction prophylaxis.PMIDTumor Lysis Syndrome.Lindsay AB et al. · Emerg Med Clin North Am 2025 · PMID 40610062Recent practical TLS review covering acute stabilization and AKI prevention at cytoreduction.
Related agents
Other agents sharing the same signature kidney injury.