Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Microtubule inhibitor
Eribulin
Halaven · Erib
A microtubule inhibitor with reduced clearance in renal impairment, not direct kidney toxicity.
MildMicrotubule inhibitor · approved 2010
Metastatic breast cancerLiposarcoma
Signature kidney injury
Prerenal / Hemodynamic AKI
Eribulin is not a recognized direct nephrotoxin. Pharmacokinetic study shows reduced clearance and ~1.5-fold higher exposure with moderate-to-severe renal impairment, supporting dose adjustment; any AKI is generally prerenal and not well quantified.
Source: Tan et al., Cancer Chemother Pharmacol 2015
Mechanism of kidney injury
No characteristic direct tubular or glomerular toxin effect. The relevant renal issue is reduced drug clearance at low GFR (increased exposure and toxicity, including myelosuppression and neuropathy); prerenal AKI arises from intercurrent volume depletion.
Clinical presentation
Renal-impairment effects are pharmacokinetic - greater exposure with more myelosuppression and neuropathy; any AKI is prerenal with bland sediment.
Onset
Exposure-related toxicity accrues across cycles; prerenal AKI follows volume loss.
Reversibility
Reversible
Anticancer mechanism
Synthetic halichondrin-B analogue that inhibits microtubule growth at the plus end (a non-taxane microtubule dynamics inhibitor distinct from the taxane binding site), sequestering tubulin and arresting cells in mitosis. Used in metastatic breast cancer and liposarcoma.
Management
Reduce dose in renal impairment to limit excess hematologic and neurologic toxicity; treat prerenal AKI supportively with volume optimization.
Risk factors
- Moderate-to-severe renal impairment (CrCl <50 mL/min - reduced clearance)
- Volume depletion and concurrent nephrotoxins
- Baseline cytopenias amplifying systemic toxicity
Prevention
- Dose-reduce for moderate/severe renal impairment per labeling
- Monitor renal function and blood counts
- Maintain hydration; minimize additive nephrotoxins
Note · Reduced clearance in renal impairment drives dosing concerns rather than intrinsic nephrotoxicity.
Clinical depth
Renal dose adjustment
Reduce dose to 1.1 mg/m2 for CrCl 30-50 mL/min (moderate impairment); PK data support this matching exposure seen at 1.4 mg/m2 with normal function. Limited data below CrCl 30 mL/min - use caution.
Dialyzability & ESKD dosing
Highly protein-bound with a large volume of distribution and predominantly hepatobiliary elimination; not expected to be dialyzable. No HD-timed dosing established.
Differential diagnosis
Pharmacokinetic over-exposure in low GFR (cytopenias/neuropathy without renal injury) vs prerenal azotemia vs unrelated CKD. The signal is dose-exposure, not parenchymal toxicity.
Monitoring
- CrCl/eGFR before dosing (drives dose level)
- CBC with differential (neutropenia) each cycle
- Peripheral neuropathy assessment; QTc per label
Key trials & series
- EMBRACE phase 3 (OS benefit in heavily pretreated metastatic breast cancer)
- Tan Cancer Chemother Pharmacol 2015 renal-impairment PK study
Clinical pearls
- Eribulin is dose-adjusted for the kidney to prevent over-exposure, not because it injures the kidney.
- Drop to 1.1 mg/m2 for CrCl 30-50 mL/min.
- Watch counts and neuropathy as the readouts of excess exposure.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Injury signatures
Prerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of microtubule inhibitors.
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.
LandmarkPharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.Tan AR et al. · Cancer Chemother Pharmacol 2015 · PMID 26433580Shows increased eribulin exposure with renal impairment and supports dose reduction to 1.1 mg/m2 for CrCl 30-50 mL/min.PMIDEribulin monotherapy versus treatment of physician's choice in patients with metastatic breast cancer (EMBRACE): a phase 3 open-label randomised study.Cortes J et al. · Lancet 2011 · PMID 21376385Registrational phase 3 trial establishing eribulin's survival benefit and characteristic toxicity profile (neutropenia, neuropathy).PMIDOnconephrology: Update in Anticancer Drug-Related Nephrotoxicity.García-Carro C et al. · Nephron 2022 · PMID 35717937Context for microtubule-inhibitor renal safety and dosing in kidney disease.PMIDOnconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin 2020 · PMID 32853404Authoritative review of chemotherapy dosing and AKI in kidney disease.
Related agents
Other agents sharing the same signature kidney injury.