How should kidney function be monitored during Etoposide therapy?

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.

How can kidney injury from Etoposide be prevented?

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

Who is at higher risk of kidney injury from Etoposide?

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).

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Printable monograph

Topoisomerase II inhibitor

Etoposide

Etopophos · VP-16

Topoisomerase II inhibitor · approved 1983 · 9 citations · FAERS AKI reporting ROR 2.59 (95% CI 2.45–2.73, 1,377 AKI reports)

Aging evidence· through 2021

Deeply sourced7/9 · 6 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 26y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
Met: Real-world FAERS signal

Describes how this page is sourced, not how dangerous the drug is. Thinly sourced means fewer of the sourcing signals are met — not that the agent is kidney-safe. A rule-based summary, not a formal certainty appraisal.

A topoisomerase II poison whose renal risk runs through tumor lysis, not the tubule.

MildTopoisomerase II inhibitor

Small-cell lung cancerTesticular/germ-cell cancerLymphomaLeukemia

§01

Signature kidney injury

Signature lesion

Crystal / Obstructive Nephropathy

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

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Tumor-lysis AKI within hours to a few days of starting cytotoxic therapy in sensitive tumors.

Distilled from: “TLS typically within hours to a few days of starting cytotoxic therapy in sensitive tumors; exposure-related myelosuppression accrues over cycles.”

§02

Renal toxicities, ranked

This agent's kidney lesions ordered by prominence — the #1 signature lesion first, then secondary and rare patterns. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Crystal / Obstructive Nephropathy#1 · Signaturequalitative — no citable incidence
Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.
Electrolyte DisturbanceSecondaryqualitative — no citable incidence
Renal electrolyte derangement — magnesium/potassium/calcium wasting (cisplatin, anti-EGFR antibodies) or retention (FGFR-inhibitor hyperphosphatemia, tumor-lysis hyperkalemia/hyperphosphatemia).

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityMild

ReversibilityReversible

Evidence9 citations

Nephron map

Vasculature / Endothelium

Distal Tubule / Collecting Duct

Tubular LumenThe urine flow path

Crystal / Obstructive Nephropathy

Intratubular precipitation of drug or metabolite — high-dose methotrexate and tumor lysis crystals.

§03

Kidney injury

Also documented as kidney-sparing

Etoposide — No direct tubular or glomerular toxicity. Partly renally cleared — dose-adjust for CrCl; tumor lysis.

The spared

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.

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.Lesion-level management framework

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

Anticancer mechanism· how it treats cancer

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.

Note · Renally cleared with tumor-lysis risk; the kidney injury is overwhelmingly TLS- and volume-mediated, not a direct etoposide tubular toxin.

§04

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%) and not cleared by hemodialysis: in the PK-guided dialysis study that dosed carboplatin and etoposide together, carboplatin was cleared by hemodialysis and etoposide was not, and peritoneal dialysis removed neither. There is therefore no post-HD supplemental dose to give. Dialysis is used for TLS-related metabolic complications, not to clear etoposide; reduce dose in renal impairment and target exposure by pharmacokinetic monitoring.

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 Hematology 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.

Beyond the kidney — non-renal toxicities· 3 organ systems

Class-level context for the major non-renal toxicities of the Topoisomerase II inhibitor class.

Neurologic

Neuropathy, encephalopathy, ICANS, PRES

Peripheral neuropathy (taxanes, vinca)

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression

Immune / Infusion

CRS, infusion reactions, irAEs, anaphylaxis

Hypersensitivity (taxane vehicles)

§05

References

6 primary references — trials, cohorts, mechanism, and reviews. Single-patient case reports are listed separately below, graded by strength. Citation metadata via PubMed / NLM.

Evidence accrual

6 references · 2001–2021 · 1 since 2019

Primary (non–case-report) references per year — a proxy for how actively the agent's renal literature is accruing. Recent years are highlighted. Reflects curation depth, not a systematic bibliometric count.

Case reports — ranked by strength· 3

Single-patient and small-series reports, graded by evidentiary strength — A Strong (biopsy-proven plus a series and/or positive rechallenge), B Moderate, and C Limited (a single clinically-diagnosed case). Strongest first. Grades are inferred automatically from each report's abstract and journal — a heuristic ranking aid, not a formal quality appraisal.

CaseB · ModerateThrombotic microangiopathy: a new dose-limiting toxicity of high-dose sequential chemotherapy.Vantelon JM et al. · Bone Marrow Transplant 2001 · PMID 11313688Case series describing thrombotic microangiopathy with Coombs-negative hemolytic anemia, thrombocytopenia and renal dysfunction in patients given high-dose sequential chemotherapy in which etoposide was the constant agent across every treatment phase.CaseB · ModerateHemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support.van der Lelie H et al. · Cancer 1995 · PMID 8635040Case series of hemolytic uremic syndrome (microangiopathic hemolytic anemia, hypertension and renal insufficiency) after high-dose chemotherapy including an etoposide-containing BEAC conditioning regimen with autologous stem cell support.CaseC · LimitedComplete recovery of renal function in a Wilms' tumor patient after acute renal failure caused by autologous bone marrow transplantation (ABMT).Hempel L et al. · Pediatr Hematol Oncol 1998 · PMID 9615324Pediatric case report of reversible acute renal failure with combined glomerular and tubular dysfunction requiring hemodialysis after an etoposide/carboplatin/melphalan conditioning regimen for autologous bone marrow transplantation.

FDA label — boxed warning & renal dosing· boxed warning

Quoted verbatim from this agent's current FDA label (Jul 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

Warnings Etoposide should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe myelosuppression with resulting infection or bleeding may occur.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 74,564 of them for this agent. Nobody counts the patients who were fine, so none of these numbers is an incidence, a risk, or a rate: they describe what gets reported, shaped by a drug's fame, its indication, and who was watching. How these numbers work.

Reporting odds ratio (ROR) — is kidney injury named in this agent's reports more often than in every other drug's? Above 1 means yes, disproportionately.
Renal phenotypes — the same question asked separately for each kind of kidney injury, so the ratios differ from the overall one and from each other.
Outcomes — a share of this agent's own reports, not of patients: how many were filed as involving a death or a hospitalization. Not a case-fatality rate.

FAERS reported renal phenotypes· 8 signals

Only significant signals appear (95% CI lower bound above 1) — a phenotype missing here was tested and did not reach significance, except Prerenal / Hemodynamic AKI, Pseudo-AKI, Renal Cysts, Chronic Interstitial Nephropathy — outside the clinician-reviewed MedDRA term map, never queried — and ATN and AIN, queried but biopsy-bound: real cases are filed as generic “acute kidney injury”, so their absence is not a negative. As of 2026-10-01.

What reporting says about this profile's documented lesions

Electrolyte Disturbancecorroborated · ROR 2.92 — on the terms that name the lesion (ROR 6.19)
Crystal / Obstructive NephropathyNo disproportionate reporting — This phenotype IS reportable and this agent has enough reports, yet the reporting is not disproportionate — the one genuinely informative negative of the four.
Prerenal / Hemodynamic AKINot queried in FAERS — No MedDRA term set is defined for this phenotype, so FAERS was never asked about it.

Thrombotic Microangiopathy

ROR 7.9995% CI 7.26–8.80· 427 reports

Fanconi Syndrome

ROR 6.4495% CI 5.35–7.75· 115 reports

Electrolyte Disturbance

ROR 2.9295% CI 2.79–3.06· 1,940 reports

SIADH / Hyponatremia

ROR 2.8595% CI 2.66–3.06· 806 reports

Acute Tubular Necrosis

ROR 2.8295% CI 2.31–3.44· 98 reports

Hemorrhagic Cystitis

ROR 2.5395% CI 2.33–2.74· 616 reports

Acute Interstitial Nephritis

ROR 2.0795% CI 1.75–2.44· 137 reports

Glomerular Injury / Proteinuria

ROR 1.7595% CI 1.51–2.02· 180 reports

FAERS outcomes & reporting trend· 24.2% of reports w/ death · 33.9% w/ hospitalization

24.2%

Reported with a death outcome

18,071 of 74,564 reports

33.9%

Reported with hospitalization

25,314 of 74,564 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 74,564 reports

Bars rank systems by summed reaction-term mentions (a report counts once per term it names) — an ordinal “more vs less reported” cue, not a tally of distinct reports. Renal & urinary first. As of 2026-10-01.

Disproportionality (acute kidney injury):ROR 2.5995% CI 2.45–2.73· 1,377 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Renal & urinary

Acute Kidney Injury1,377

Blood & lymphatic

Febrile Neutropenia7,773Neutropenia5,108Thrombocytopenia4,169Anaemia3,408Pancytopenia2,813

Gastrointestinal

Nausea2,505Mucosal Inflammation2,326Diarrhoea2,324Vomiting2,176

Immune / infection

Sepsis3,074Pneumonia2,540Infection2,051Septic Shock1,602

General / constitutional

Pyrexia3,494Fatigue1,508

Respiratory

Dyspnoea1,574Respiratory Failure1,324

Guidelines & consensus· 13

Each recommendation below is this atlas's faithful summary of the source, not a quotation from it — follow the PubMed link for the wording the society published. Summaries may be superseded; consult the current full text and individualize to the patient.

General onco-nephrology references

ADQIThe nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupNat Rev Nephrol 2026 · PMID 41361704Provides expert-based statements (modified Delphi) on preventing and managing cisplatin/platinum-associated AKI, including isotonic IV hydration, attention to volume status and concomitant nephrotoxins, and incorporates evidence that IV magnesium supplementation may reduce cisplatin-associated AKI; emphasizes risk stratification and standardized AKI definitions.SIRMSIRM-SIN-AIOM: appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations-consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)Radiol Med 2022 · PMID 35303246Recommends eGFR-based renal risk assessment and pre/post-contrast isotonic saline or sodium bicarbonate hydration; advises maintaining a 5-7 day interval between iodinated contrast administration and cisplatin in cancer patients to reduce additive nephrotoxicity.KDIGOKDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerKidney Int 2020 · PMID 33126977Identifies platinum compounds (especially cisplatin) as leading cytotoxic causes of acute tubular injury, AKI, and electrolyte/magnesium wasting; calls for interdisciplinary onco-nephrology care, accurate GFR estimation, and individualized drug dosing in patients with reduced kidney function.KDIGOKDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationKidney Int 2020 · PMID 33276867Addresses chemotherapy-associated AKI/CKD in hematologic cancer, GFR estimation and chemotherapy dosing in patients with reduced kidney function, and management priorities and research gaps for onco-nephrology care.ADDIKDIntegrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceEClinicalMedicine 2025 · PMID 40290844Provides GRADE-based, drug-specific dose-adjustment recommendations for anticancer agents in kidney dysfunction (illustrated for methotrexate, cisplatin, carboplatin and nivolumab); the recommendations build on Part 1's standardised CKD-EPI eGFR assessment rather than Cockcroft-Gault creatinine clearance.ADDIKDAligning kidney function assessment in patients with cancer to global practices in internal medicineEClinicalMedicine 2025 · PMID 40290845Three consensus recommendations: assess kidney function by GFR (measured GFR or CKD-EPI eGFR), classify it using KDIGO categories, and use this uniform approach to dose anticancer drugs — moving cancer medicine away from Cockcroft-Gault estimated creatinine clearance.ADDIKDA methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEClinicalMedicine 2025 · PMID 40290846Establishes that, where RCT evidence is lacking, anticancer drug dosing recommendations in kidney dysfunction should be derived by critically appraising observational literature via GRADE combined with structured international multidisciplinary consensus voting.KDIGODiagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Crit Care 2013 · PMID 23394211Defines/stages AKI by serum creatinine and urine output; emphasizes avoiding nephrotoxins, maintaining euvolemia/perfusion, dose-adjusting drugs to kidney function, and monitoring high-risk patients — the framework applied to nephrotoxic anti-cancer agents.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsKidney Int 2024 · PMID 38519239Evaluate and risk-stratify CKD, manage to delay progression and its complications, and practise explicit medication management and drug stewardship — the framework the atlas's G1–G5 eGFR banding and every renal dose-adjustment recommendation sit inside. Because the guideline excludes dialysis and transplant recipients by its own statement of scope, its recommendations do not carry to those settings, where this atlas's dialyzability and post-transplant guidance rests on other sources.KDIGOExecutive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesKidney Int 2021 · PMID 34556300Provides the staging/treatment framework for drug-associated glomerular lesions (e.g., bisphosphonate- and interferon-related collapsing FSGS, VEGF-inhibitor podocytopathy/proteinuria), including immunosuppression and supportive RAAS-blockade strategies.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisKidney Int 2024 · PMID 38388147Updates immunosuppressive induction (rituximab/cyclophosphamide), incorporates avacopan and lower-dose or glucocorticoid-sparing regimens — the management framework for drug- and checkpoint-inhibitor-associated ANCA/pauci-immune glomerulonephritis.KDIGOExecutive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisKidney Int 2024 · PMID 38182299Updates first-line lupus nephritis therapy to combination immunosuppression with the addition of belimumab or a calcineurin inhibitor (voclosporin) — informs management of immune-complex/lupus-like glomerulonephritis encountered with immunotherapy.KDIGOExecutive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Kidney Int 2025 · PMID 40975525Encourages liberal kidney biopsy and stricter proteinuria control (<0.5 g/d, ideally <0.3 g/d) with RAAS blockers, SGLT2 inhibitors, and targeted-release budesonide — the framework for IgA-dominant glomerular lesions, including those triggered by immune-modulating cancer therapy.

Where Etoposide sits in nephrotoxicity space — each dot is an anti-cancer agent, positioned so neighbors share a kidney-injury phenotype. Its 6 closest are filled and lead to a numbered marker, matching the numbered cards below.

Position is a 2-D projection (MDS) of each agent's injury signature, nephron target, severity, and class, so two dots can sit close on the page while differing on an axis the projection flattened — the numbered ranking is computed from the full metric, not from the distance you see. Open the full map.

Phenotype-similar agents· the numbered markers on the map above

Hydroxyurea

Hydrea · Ribonucleotide reductase inhibitor

Profile

Tumor lysis in myeloproliferative disease.

XTALPRELYTE

Mild#1 · 89% phenotype match

Nelarabine

Arranon · Purine analog

Profile

Tumor lysis in T-ALL.

XTALPRELYTE

Mild#2 · 89% phenotype match

Pomalidomide

Pomalyst · Immunomodulatory drug (IMiD)

Profile

Tumor lysis; usable in renal impairment.

PRELYTEXTAL

Mild#3 · 89% phenotype match

Thalidomide

Thalomid · Immunomodulatory drug (IMiD)

Profile

Tumor lysis and bradycardia.

PRELYTEXTAL

Mild#4 · 89% phenotype match

Cladribine

Leustatin · Purine analog

Profile

Tumor lysis; high-dose nephrotoxicity.

XTALPRELYTE

Mild#5 · 89% phenotype match

Ibritumomab tiuxetan

Zevalin · Radioimmunotherapy (Y-90 anti-CD20)

Profile

Yttrium-90 radioimmunotherapy; tumor lysis with bulky lymphoma.

PREXTALLYTE

Mild#6 · 88% phenotype match

Compare Etoposide with its nearest agents

Nearest agents by kidney-injury phenotype (shared injuries, nephron target, severity, class) — a similarity approximation, not a claim of shared drug identity or mechanism.

Kidney risk across Topoisomerase inhibitors

Same-class agents ordered by their documented kidney-injury profile — atlas severity, an acute-kidney-injury FAERS signal, and how many injury types each is documented to cause. Agents nearer the top carry the lighter documented renal profile.

1TopotecanPRE — Prerenal / Hemodynamic AKIMild
2TeniposideLYTE — Electrolyte DisturbanceMild
3IrinotecanPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
4Etoposide· this agentXTAL — Crystal / Obstructive NephropathyFAERS AKIMild
5AmsacrineLYTE — Electrolyte DisturbanceModerate

A comparison of documented kidney-injury data within one drug class — not a substitution recommendation. Efficacy, indication, and non-renal toxicity differ between these agents and are out of scope here. Educational only, not medical advice.

Who studies this

The leading contributors to Etoposide’s clinical kidney literature on PubMed, ranked by a blend of publication volume and citation impact — filtered toward clinical work via the PubMed Humans heading and clinical publication types (trials, cohorts, case reports, guidelines, reviews). Names link to that author’s work on Etoposide; the PMIDs beside each name are up to three of their most recent papers on it, not the full count.

Ranked by a 50/50 blend of publication volume and a position-weighted, capped Relative Citation Ratio (NIH iCite) on this agent’s renal literature; the citation count shown is the raw total, not the ranking score — counted over the 116 clinical records among the 300 most-relevant of 433 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.