What kind of kidney injury does Irinotecan 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 Irinotecan therapy?

Stool frequency and hydration status each cycle; Serum creatinine/BUN and electrolytes with significant diarrhea; CBC for neutropenia; UGT1A1 genotype before first dose where available.

How can kidney injury from Irinotecan be prevented?

Aggressive antidiarrheal management (high-dose loperamide for delayed diarrhea; atropine for acute cholinergic symptoms) Patient education and early oral/IV rehydration at first loose stools Consider UGT1A1 genotyping; reduce starting dose to ~70% in confirmed poor metabolizers

Who is at higher risk of kidney injury from Irinotecan?

Severe or unmanaged delayed diarrhea; UGT1A1 poor-metabolizer genotype (*28/*28, *6, *37) - higher SN-38 exposure; ABCG2 c.421C>A and other transporter variants; Older age, baseline volume depletion, concurrent diuretics.

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Printable monograph

Topoisomerase I inhibitor

Irinotecan

Camptosar · Irino

Topoisomerase I inhibitor · approved 1996 · 5 citations · FAERS AKI reporting ROR 1.60 (95% CI 1.36–1.88, 148 AKI reports)

Recent· through 2024

Fairly sourced4/9 · 4 signals

Not met: 5 citations
Not met: 12+ references
Not met: Accrued over 10+ years (span: 4y)
Met: Beyond single case reports
Not met: Peer-reviewed sources
Met: Landmark reference
Met: Current through 2024
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 I poison whose severe diarrhea is the real threat to the kidneys.

MildTopoisomerase I inhibitor

Colorectal cancerPancreatic cancerGastric cancer

§01

Signature kidney injury

Signature lesion

Prerenal / Hemodynamic AKI

Direct nephrotoxicity is not a recognized feature; the principal renal risk is prerenal AKI from severe early (cholinergic) and delayed diarrhea with volume depletion. Severe (grade 3-4) irinotecan toxicity, mostly diarrhea/neutropenia, occurs in roughly a quarter to a third of patients and is enriched in UGT1A1 poor metabolizers. AKI incidence specifically attributable to irinotecan is not well quantified.Source: Hulshof et al., Eur J Hum Genet 2022

Onset & rechallenge

Time to injuryAcute (~1–7 days)

Delayed diarrhea from ~24 hours and over subsequent days, with AKI following the cumulative volume loss.

Distilled from: “Acute cholinergic diarrhea within hours of infusion; delayed diarrhea after ~24 hours and over subsequent days, with AKI following cumulative 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

Also documented as kidney-sparing

Irinotecan — Hepatic (UGT1A1) metabolism; no direct renal lesion. Severe diarrhea can cause INDIRECT prerenal AKI.

The spared

Mechanism of kidney injury

Volume depletion from profuse SN-38-mediated secretory diarrhea (plus vomiting and poor intake) reduces effective circulating volume and renal perfusion, producing prerenal azotemia that can progress to ischemic ATN if uncorrected. The drug does not directly injure tubular cells at usual exposures; impaired SN-38 glucuronidation (UGT1A1*28/*6/*37) raises active-metabolite exposure and the severity of the diarrhea.

Clinical presentation

Watery diarrhea, orthostasis, decreased urine output, and rising BUN/creatinine with a high BUN:creatinine ratio and bland sediment; urine is concentrated (low FeNa) consistent with prerenal physiology. Early cholinergic syndrome (diaphoresis, cramping, lacrimation) reverses with atropine.

Management

Restore volume with IV crystalloid, control diarrhea, and hold chemotherapy until recovery. Prerenal AKI typically reverses promptly once euvolemia is restored; persistent injury warrants evaluation for ischemic ATN.Lesion-level management framework

Risk factors

Severe or unmanaged delayed diarrhea
UGT1A1 poor-metabolizer genotype (*28/*28, *6, *37) - higher SN-38 exposure
ABCG2 c.421C>A and other transporter variants
Older age, baseline volume depletion, concurrent diuretics

Prevention

Aggressive antidiarrheal management (high-dose loperamide for delayed diarrhea; atropine for acute cholinergic symptoms)
Patient education and early oral/IV rehydration at first loose stools
Consider UGT1A1 genotyping; reduce starting dose to ~70% in confirmed poor metabolizers

Anticancer mechanism· how it treats cancer

Prodrug converted by carboxylesterases (CES1/CES2) to the active metabolite SN-38, which stabilizes the topoisomerase I-DNA cleavable complex, causing lethal double-strand breaks during DNA replication. Used in colorectal, pancreatic, and other gastrointestinal cancers (FOLFIRI, FOLFIRINOX).

Note · Kidney injury is essentially diarrhea-driven and prerenal; preventing and treating diarrhea is the key renal-protective step.

§04

Clinical depth

Renal dose adjustment

Largely hepatic/biliary elimination, so no formal eGFR-based renal dose table — but the FDA label advises caution in renal impairment and directs not using irinotecan in patients on dialysis. UGT1A1 poor metabolizers warrant a ~30% starting-dose reduction. Caution and possible reduction in significant hepatic dysfunction (hyperbilirubinemia).

Dialyzability & ESKD dosing

Irinotecan and SN-38 are protein-bound and hepatically/biliary cleared; not effectively removed by dialysis, and the FDA label directs not using irinotecan in patients on dialysis.

Differential diagnosis

Diarrhea-driven prerenal AKI (volume signs, low FeNa, bland urine) vs C. difficile or neutropenic enterocolitis vs concurrent nephrotoxin ATN. The temporal link to delayed diarrhea and rapid reversal with fluids is characteristic.

Monitoring

Stool frequency and hydration status each cycle
Serum creatinine/BUN and electrolytes with significant diarrhea
CBC for neutropenia
UGT1A1 genotype before first dose where available

Key trials & series

DPWG UGT1A1-irinotecan pharmacogenetic guideline (Hulshof 2022)
FOLFIRINOX and FOLFIRI registrational regimens

Clinical pearls

Atropine treats the acute cholinergic diarrhea; loperamide treats the delayed diarrhea - they are different syndromes.
UGT1A1 poor metabolizers get worse diarrhea and thus more prerenal AKI; genotype-guided dose reduction helps.
The kidney is collateral damage from gut fluid loss - the renal-protective intervention is controlling diarrhea early.

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

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

Evidence accrual

5 references · 2020–2024 · 3 since 2022

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 (May 2026) — not paraphrased or interpreted. Full label on DailyMed .

Boxed warning

WARNING: DIARRHEA and MYELOSUPPRESSION • Early and late forms of diarrhea can occur. Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine. Late diarrhea can be life threatening and should be treated promptly with loperamide. Monitor patients with diarrhea and give fluid and electrolytes as needed. Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia. Interrupt CAMPTOSAR and reduce subsequent doses if severe diarrhea occurs [see Dosage and Administration (2.2) and Warnings and Precautions (5.1) ] . • Severe myelosuppression may occur [see Warnings and Precautions (5.2) ] . WARNING: DIARRHEA and MYELOSUPPRESSION See full prescribing information for complete boxed warning . • Early and late forms of diarrhea can occur. Early diarrhea may be accompanied by cholinergic symptoms which may be prevented or ameliorated by atropine. Late diarrhea can be life threatening and should be treated promptly with loperamide. Monitor patients with diarrhea and give fluid and electrolytes as needed. Institute antibiotic therapy if patients develop ileus, fever, or severe neutropenia. Interrupt CAMPTOSAR and reduce subsequent doses if severe diarrhea occurs. ( 2.2 , 5.1 ) • Severe myelosuppression may occur. ( 5.2 )

Renal impairment — from the label

Use caution and do not use in patients on dialysis. ( 8.6 )

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 12,781 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· 5 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.

Glomerular Injury / Proteinuria

ROR 6.4495% CI 5.35–7.75· 113 reports

Electrolyte Disturbance

ROR 4.0895% CI 3.71–4.47· 461 reports

SIADH / Hyponatremia

ROR 2.9095% CI 2.45–3.42· 141 reports

Crystal / Obstructive Nephropathy

ROR 1.6295% CI 1.25–2.12· 55 reports

Hypertension

ROR 1.2795% CI 1.13–1.42· 296 reports

FAERS outcomes & reporting trend· 20.6% of reports w/ death · 40.8% w/ hospitalization

20.6%

Reported with a death outcome

2,633 of 12,781 reports

40.8%

Reported with hospitalization

5,212 of 12,781 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 7 systems · 12,781 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 1.6095% CI 1.36–1.88· 148 AKI reports ·AKI is reported disproportionately more often than for other drugs (CI entirely above 1) — a hypothesis-generating signal, not proof of causation.

Gastrointestinal

Diarrhoea1,721Nausea946Vomiting847Abdominal Pain463Stomatitis258

Blood & lymphatic

Myelosuppression686Neutropenia618Febrile Neutropenia612Neutrophil Count Decreased377Anaemia371

General / constitutional

Fatigue577Pyrexia551Asthenia501Malaise260

Metabolic & electrolyte

Decreased Appetite396Dehydration363

Nervous system

Neuropathy Peripheral466

Respiratory

Dyspnoea298

Immune / infection

Sepsis250

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 Irinotecan 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

Topotecan

Hycamtin · Topoisomerase I inhibitor

Profile

Renally cleared; dose-adjust for CrCl.

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 Irinotecan 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
3Irinotecan· this agentPRE — 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 Irinotecan’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 Irinotecan; 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 103 clinical records among all 137 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.