Bendamustine
Treanda · Alkylator
Tumor lysis-mediated AKI is the principal risk; TMA is rare.
PRETMALYTE
ModerateOpen →
Topoisomerase II inhibitor
Etoposide
Etopophos · VP-16
A topoisomerase II poison whose renal risk runs through tumor lysis, not the tubule.
MildTopoisomerase II inhibitor · approved 1983
Small-cell lung cancerTesticular/germ-cell cancerLymphomaLeukemia
Signature kidney injury
Prerenal / Hemodynamic AKI
Etoposide is renally cleared (~30-40% as unchanged drug, so dose-adjust in renal impairment) and is a frequent component of regimens for bulky, rapidly proliferating tumors that can trigger tumor lysis syndrome (TLS). Direct etoposide nephrotoxicity is not a recognized signal; TLS-related AKI risk depends on tumor burden and tumor type rather than a per-drug rate.
Source: Howard et al., N Engl J Med 2011
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
When highly chemosensitive tumors lyse, released purines are catabolized to uric acid and released phosphate binds calcium; uric acid and calcium-phosphate precipitate intratubularly, causing crystal/obstructive AKI alongside hyperkalemia and hypocalcemia. Etoposide itself is not a characteristic tubular toxin; additional prerenal contributions arise from nausea, vomiting, and poor intake.
Clinical presentation
In TLS: hyperuricemia, hyperphosphatemia, hyperkalemia, and hypocalcemia with rising creatinine and oliguria, typically within 12-72 hours of cytotoxic therapy. A high uric-acid:creatinine ratio in urine supports urate nephropathy. Otherwise the renal picture is bland.
Onset
TLS typically within hours to a few days of starting cytotoxic therapy in sensitive tumors; exposure-related myelosuppression accrues over cycles.
Reversibility
Reversible
Anticancer mechanism
Inhibits topoisomerase II, stabilizing enzyme-DNA complexes and causing double-strand DNA breaks. Backbone agent in germ-cell tumors, small-cell lung cancer, lymphomas, and leukemias.
Management
Treat TLS with vigorous hydration, rasburicase for hyperuricemia, electrolyte correction (avoid calcium unless symptomatic hypocalcemia), and renal replacement therapy for refractory hyperkalemia, hyperphosphatemia, or oliguric AKI. Provide supportive care and adjust dosing for renal impairment.
Risk factors
- High tumor burden / rapidly proliferating malignancy (acute leukemia, high-grade lymphoma, germ-cell tumor)
- Elevated baseline uric acid and LDH
- Pre-existing renal impairment, oliguria, or volume depletion
- Renal impairment also raises etoposide exposure (free fraction increases with hypoalbuminemia/low GFR)
Prevention
- Risk-stratified TLS prophylaxis: aggressive IV hydration plus allopurinol (intermediate risk) or rasburicase (high risk/established hyperuricemia)
- Frequent monitoring of potassium, phosphate, calcium, uric acid, and creatinine around initiation
- Dose-adjust etoposide for creatinine clearance
Note · Renally cleared with tumor-lysis risk; the kidney injury is overwhelmingly TLS- and volume-mediated, not a direct etoposide tubular toxin.
Clinical depth
Renal dose adjustment
Reduce dose for renal impairment: roughly 75% of dose for CrCl 15-50 mL/min and consider further reduction below 15 mL/min, because renal clearance contributes meaningfully and hypoalbuminemia raises free drug.
Dialyzability & ESKD dosing
Highly protein-bound (~95%); only modestly removed by hemodialysis. Dialysis is used for TLS-related metabolic complications, not to clear etoposide; give dose after HD on dialysis days if used.
Differential diagnosis
TLS-associated AKI (the hyperuricemia/hyperphosphatemia/hyperkalemia/hypocalcemia tetrad with high LDH) vs prerenal azotemia vs contrast or nephrotoxin ATN. The metabolic signature distinguishes TLS.
Monitoring
- Uric acid, potassium, phosphate, calcium, and creatinine every 6-12 h during high-risk TLS windows
- Urine output and volume status
- CrCl before dosing; CBC for myelosuppression
Key trials & series
- Howard NEJM 2011 TLS definition/management framework
- British Committee for Standards in Haematology TLS guidelines (Cairo-Bishop classification)
Clinical pearls
- Etoposide does not poison the tubule - the tumor it lyses does, via urate and calcium-phosphate crystals.
- Rasburicase, not urinary alkalinization, is preferred for high-risk hyperuricemia (and avoid alkalinization, which worsens calcium-phosphate deposition).
- Low albumin raises free etoposide - reduce dose in renal impairment and hypoalbuminemia.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Tubular Lumen
The urine flow path
Injury signatures
Prerenal / Hemodynamic AKICrystal / Obstructive NephropathyElectrolyte Wasting
Beyond the kidney
Class-level context for the major non-renal toxicities of topoisomerase ii 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
6 peer-reviewed references. Citation metadata via PubMed / NLM.
LandmarkThe tumor lysis syndrome.Howard SC et al. · N Engl J Med 2011 · PMID 21561350Definitive review of TLS pathophysiology, risk stratification, and management, including urate/calcium-phosphate crystal AKI.PMIDRational use of rasburicase for the treatment and management of tumor lysis syndrome.Shaikh SA et al. · J Oncol Pharm Pract 2017 · PMID 28077046Evaluates rasburicase dosing strategies and renal outcomes (AKI, dialysis) in TLS.PMIDAcute tumor lysis syndrome in solid tumors--a case report and review of the literature.Baeksgaard L et al. · Cancer Chemother Pharmacol 2003 · PMID 12655435Reviews TLS with renal failure including an etoposide/cisplatin regimen, highlighting risk in chemosensitive tumors.PMIDTumor lysis syndrome in an infant with Langerhans cell histiocytosis successfully treated using continuous arteriovenous hemofiltration.Jaing TH et al. · J Pediatr Hematol Oncol 2001 · PMID 11216709Case of TLS with oliguric acute renal failure after an etoposide-containing regimen requiring renal replacement therapy.PMIDAnalysis of the 2015 British guidelines on the prevention and management of tumor lysis syndrome.Dupré A et al. · Rev Med Interne 2016 · PMID 27659746Practical appraisal of TLS prophylaxis and renal-protective management guidelines.PMIDOnconephrology.Kala J et al. · Crit Care Clin 2021 · PMID 33752861Onconephrology review covering tumor lysis syndrome and chemotherapy-associated AKI.
Related agents
Other agents sharing the same signature kidney injury.