What kind of kidney injury does Topotecan cause?

Prerenal / Hemodynamic AKI — Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

How should kidney function be monitored during Topotecan therapy?

CBC with differential (nadir counts) before each cycle; Volume status in patients with diarrhea or poor intake.

How can kidney injury from Topotecan be prevented?

Dose-adjust for creatinine clearance per labeling (reduced dose for CrCl 20-39 mL/min)

Who is at higher risk of kidney injury from Topotecan?

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).

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Printable monograph

Topoisomerase I inhibitor

Topotecan

Hycamtin · Topo

Topoisomerase I inhibitor · approved 1996 · 4 citations

Aging evidence· through 2022

Thinly sourced2/9 · 2 signals

Not met: 4 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 7y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Not met: Current through 2022
Not 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 renally cleared topoisomerase I inhibitor that demands dose-adjustment, not a direct kidney toxin.

MildTopoisomerase I inhibitor

Ovarian cancerSmall-cell lung cancerCervical cancer

§01

Signature kidney injury

Signature lesion

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

Onset & rechallenge

Time to injuryVariable / unpredictable

Hematologic toxicity manifests across treatment cycles and prerenal AKI follows whenever intercurrent volume loss occurs.

Distilled from: “Exposure-related hematologic toxicity manifests across treatment cycles; prerenal AKI follows intercurrent volume loss.”

§02

Renal toxicities, ranked

This agent's defining kidney lesion — its #1 signature. Cited incidence is shown where a citable figure exists; otherwise the tier stands qualitatively.

Prerenal / Hemodynamic AKI#1 · Signaturequalitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

§03

Kidney injury

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.

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.Lesion-level management framework

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)

Anticancer mechanism· how it treats cancer

Camptothecin analog 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.

Note · Renally cleared; dose-adjust for CrCl. The renal concern is pharmacokinetic exposure and resulting myelosuppression rather than intrinsic nephrotoxicity.

§04

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

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 & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Prerenal / Hemodynamic AKI

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

Class-level context for the major non-renal toxicities of the Topoisomerase I 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

4 primary references — trials, cohorts, mechanism, and reviews. Citation metadata via PubMed / NLM.

Evidence accrual

4 references · 2015–2022 · 3 since 2020

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.

FDA label — boxed warning & renal dosing· boxed warning · renal impairment

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

Boxed warning

WARNING: MYELOSUPPRESSION Topotecan hydrochloride can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts of greater than or equal to 1,500/mm 3 and platelet counts greater than or equal to 100,000/mm 3 . Monitor blood cell counts [see Warnings and Precautions ( 5.1 )]. WARNING: MYELOSUPPRESSION See full prescribing information for complete boxed warning. Topotecan hydrochloride can cause severe myelosuppression. Administer first cycle only to patients with baseline neutrophil counts greater than or equal to 1,500/mm 3 and platelet counts greater than or equal to 100,000/mm 3 . Monitor blood cell counts. ( 2.4 , 5.1 )

Renal impairment — from the label

Reduce the dose of topotecan hydrochloride for injection in patients with a CLcr of 20 to 39 mL/min [see Dosage and Administration ( 2.6 ), Clinical Pharmacology ( 12.3 )] . No dosage adjustment is recommended for patients with CLcr greater than or equal to 40 mL/min. Insufficient data are available in patients with CLcr less than 20 mL/min to provide a dosage recommendation for topotecan hydrochloride for injection.

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 6,854 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· 7 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

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 5.7695% CI 4.00–8.30· 29 reports

Electrolyte Disturbance

ROR 3.8395% CI 3.36–4.37· 233 reports

SIADH / Hyponatremia

ROR 3.7795% CI 3.08–4.60· 98 reports

Crystal / Obstructive Nephropathy

ROR 3.0995% CI 2.38–4.03· 56 reports

Glomerular Injury / Proteinuria

ROR 2.9595% CI 2.04–4.28· 28 reports

Hemorrhagic Cystitis

ROR 2.7195% CI 2.11–3.49· 61 reports

Acute Tubular Necrosis

ROR 2.1895% CI 1.04–4.58· 7 reports

FAERS outcomes & reporting trend· 23.9% of reports w/ death · 37.8% w/ hospitalization

23.9%

Reported with a death outcome

1,640 of 6,854 reports

37.8%

Reported with hospitalization

2,591 of 6,854 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 6 systems · 6,854 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 0.8095% CI 0.59–1.09· 40 AKI reports ·no disproportionate AKI reporting signal (CI spans 1).

Blood & lymphatic

Febrile Neutropenia602Anaemia576Neutropenia557Thrombocytopenia447White Blood Cell Count Decreased325

Gastrointestinal

Nausea459Vomiting429Diarrhoea321Abdominal Pain175

General / constitutional

Pyrexia446Fatigue335Asthenia164Pain162

Respiratory

Dyspnoea209

Metabolic & electrolyte

Decreased Appetite198

Immune / infection

Pneumonia148

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 Topotecan 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

Irinotecan

Camptosar · Topoisomerase I inhibitor

Profile

Diarrhea-driven prerenal AKI.

PRE

Mild#1 · 100% phenotype match

Asparaginase

Elspar · Enzyme

Profile

Rare AKI; pancreatitis-mediated.

PRE

Mild#2 · 89% phenotype match

Belzutifan

Welireg · HIF-2α inhibitor

Profile

Anemia/hypoxia; emerging renal profile in VHL/RCC.

PRE

Mild#3 · 89% phenotype match

Dacarbazine

DTIC · Alkylator

Profile

Rare hepatic veno-occlusive disease; minimal direct renal injury.

PRE

Mild#4 · 89% phenotype match

Eribulin

Halaven · Microtubule inhibitor

Profile

Reduced clearance in renal impairment.

PRE

Mild#5 · 89% phenotype match

Mirvetuximab soravtansine

Elahere · Antibody-drug conjugate (FRα/DM4)

Profile

Ocular toxicity dominates; renal involvement indirect/case-level (GI volume loss).

PRE

Mild#6 · 89% phenotype match

Compare Topotecan 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.

1Topotecan· this agentPRE — Prerenal / Hemodynamic AKIMild
2TeniposideLYTE — Electrolyte DisturbanceMild
3IrinotecanPRE — Prerenal / Hemodynamic AKIFAERS AKIMild
4EtoposideXTAL — 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 Topotecan’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 Topotecan; 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 20 clinical records among all 31 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.