Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Topoisomerase I inhibitor
Topotecan
Hycamtin · Topo
A renally cleared topoisomerase I inhibitor that demands dose-adjustment, not a direct kidney toxin.
MildTopoisomerase I inhibitor · approved 1996
Ovarian cancerSmall-cell lung cancerCervical cancer
Signature kidney injury
Prerenal / Hemodynamic AKI
Topotecan is substantially renally cleared, so impaired kidney function increases drug exposure and myelosuppression risk; pharmacokinetic studies show topotecan AUC rises ~109% (moderate) and ~174% (severe impairment), supporting dose reduction. Direct topotecan-induced nephrotoxicity is not a recognized signal, and drug-attributable AKI incidence is not well quantified.
Source: Devriese et al., Br J Clin Pharmacol 2015
Mechanism of kidney injury
No characteristic direct tubular or glomerular toxin effect. The clinical issue is reduced renal clearance in low-GFR patients, raising systemic exposure and hematologic toxicity; renal injury, when seen, is generally prerenal from intercurrent volume depletion or comorbidity.
Clinical presentation
Renal-impairment effects are primarily pharmacokinetic - greater and more prolonged myelosuppression (neutropenia, thrombocytopenia). Any AKI is usually prerenal with bland sediment.
Onset
Exposure-related hematologic toxicity manifests across treatment cycles; prerenal AKI follows intercurrent volume loss.
Reversibility
Reversible
Anticancer mechanism
Camptothecin analogue that inhibits topoisomerase I, trapping the enzyme-DNA cleavable complex and generating replication-associated DNA strand breaks. Used in ovarian cancer, small-cell lung cancer, and cervical cancer.
Management
Reduce dose in renal impairment to limit excess myelosuppression; treat prerenal AKI with volume repletion and supportive care. Support counts (G-CSF, transfusion) as needed.
Risk factors
- Baseline renal impairment (reduced clearance, higher AUC)
- Prior platinum-based chemotherapy (additive myelosuppression)
- Volume depletion and concurrent nephrotoxins
- Asian ancestry (higher AUC at equivalent renal function in PK data)
Prevention
- Dose-adjust for creatinine clearance per labeling (reduced dose for CrCl 20-39 mL/min)
- Monitor renal function and blood counts before each cycle
- Maintain hydration; minimize additive nephrotoxins
Note · Renally cleared; dose-adjust for CrCl. The renal concern is pharmacokinetic exposure and resulting myelosuppression rather than intrinsic nephrotoxicity.
Clinical depth
Renal dose adjustment
IV topotecan: no change for CrCl >=40 mL/min; reduce dose for CrCl 20-39 mL/min. Oral topotecan PK data support reduced doses in moderate-severe impairment. Insufficient data for CrCl <20 mL/min.
Dialyzability & ESKD dosing
Low molecular weight and renally cleared, so some removal by hemodialysis is plausible, but formal HD-timed dosing is not established; if used in dialysis patients, reduce dose and monitor counts closely.
Differential diagnosis
Pharmacokinetic over-exposure (cytopenias without AKI) vs prerenal azotemia vs unrelated CKD. The signal here is hematologic toxicity from under-cleared drug, not renal parenchymal injury.
Monitoring
- CrCl/eGFR before each cycle
- CBC with differential (nadir counts) before each cycle
- Volume status in patients with diarrhea or poor intake
Key trials & series
- Devriese Br J Clin Pharmacol 2015 oral topotecan renal-impairment PK study
Clinical pearls
- The renal issue with topotecan is dosing, not nephrotoxicity - reduce the dose, do not fear the kidney.
- Under-clearance shows up as deeper, longer cytopenias, so check CrCl before dosing.
- Prior platinum compounds the myelosuppression risk in renally impaired patients.
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 topoisomerase i 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.
LandmarkPharmacodynamics and pharmacokinetics of oral topotecan in patients with advanced solid tumours and impaired renal function.Devriese LA et al. · Br J Clin Pharmacol 2015 · PMID 25677219Demonstrates increased topotecan exposure/toxicity with renal impairment and defines recommended dose reductions.PMIDOnconephrology.Kala J et al. · Crit Care Clin 2021 · PMID 33752861Context for chemotherapy dosing and AKI mechanisms in patients with kidney disease.PMIDOnconephrology: Update in Anticancer Drug-Related Nephrotoxicity.García-Carro C et al. · Nephron 2022 · PMID 35717937Reviews chemotherapy renal safety and dose-adjustment principles in kidney disease.PMIDOnconephrology: The intersections between the kidney and cancer.Rosner MH et al. · CA Cancer J Clin 2020 · PMID 32853404Authoritative review of drug dosing and AKI in patients with cancer and kidney disease.
Related agents
Other agents sharing the same signature kidney injury.