What kind of kidney injury does 5-Fluorouracil cause?

Thrombotic Microangiopathy — Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF. Other reported patterns: Prerenal / Hemodynamic AKI.

How should kidney function be monitored during 5-Fluorouracil therapy?

CBC, LDH, haptoglobin and creatinine - rising LDH with thrombocytopenia signals TMA; Volume/diarrhea status each cycle; DPYD genotype or phenotype where available before fluoropyrimidine start.

How can kidney injury from 5-Fluorouracil be prevented?

Recognize mitomycin as the dominant TMA driver and cap its cumulative dose Hydration and prompt management of GI toxicity Consider DPYD genotyping before fluoropyrimidine start

Who is at higher risk of kidney injury from 5-Fluorouracil?

Concurrent mitomycin C (dominant TMA driver); Cumulative mitomycin/fluoropyrimidine exposure; Volume depletion from diarrhea/mucositis; DPD (DPYD) deficiency for severe systemic toxicity.

Back to explorer

Printable monograph

Pyrimidine analog

5-Fluorouracil

Adrucil · 5-FU

Pyrimidine analog · approved 1962 · 9 citations · FAERS AKI reporting ROR 2.12 (95% CI 2.00–2.25, 1,171 AKI reports)

Recent· through 2024

Deeply sourced8/9 · 7 signals

Met: 9 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 37y)
Met: Beyond single case reports
Met: High-impact journal
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 GI-cancer mainstay that is mostly kidney-safe until it teams up with mitomycin.

MildFluoropyrimidine antimetabolite

Colorectal cancerGastric and pancreatic cancerBreast cancerHead and neck cancer

§01

Signature kidney injury

Signature lesion

Thrombotic Microangiopathy

Intrinsic nephrotoxicity is low; the recognized vascular renal complication is thrombotic microangiopathy/hemolytic-uremic syndrome, classically with mitomycin C, with 5-FU as a frequent co-agent. In TTP/HUS series the most common antecedent chemotherapy is mitomycin C plus 5-FU.Source: Martinez Frances et al., Med Clin (Barc) 1997

Onset & rechallenge

Time to injuryDelayed (>6 weeks / cumulative)

TMA typically delayed (weeks to months); prerenal effects can be acute with GI toxicity.

Distilled from: “TMA often delayed (weeks to months); prerenal effects acute with GI toxicity.”

§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.

Thrombotic Microangiopathy#1 · Signaturequalitative — no citable incidence
Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.
Prerenal / Hemodynamic AKISecondaryqualitative — 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

5-Fluorouracil — Generally renally well tolerated as a single agent. Rare TMA when combined with mitomycin; mucositis, cardiotoxicity.

The spared

Appears in 1 documented synergy combination

Mechanism of kidney injury

5-FU itself is largely renally well tolerated; in combination (especially with mitomycin C) it contributes to chemotherapy-associated thrombotic microangiopathy via endothelial injury, with glomerular capillary fibrin thrombi, microangiopathic hemolysis and progressive renal failure that may appear months into therapy. Severe diarrhea/mucositis can cause prerenal AKI. Preclinically, 5-FU can induce direct renal oxidative/apoptotic tubular injury (p53/Bax/caspase-3, KIM-1), though this is not the dominant clinical lesion. DPD deficiency markedly amplifies systemic (not specifically renal) toxicity.

Clinical presentation

In TMA/HUS: microangiopathic hemolytic anemia (schistocytes, elevated LDH), thrombocytopenia and progressive renal failure, sometimes months after starting therapy and often dose-cumulative with mitomycin; otherwise prerenal azotemia from GI losses.

Management

Discontinue offending agents for TMA/HUS and provide supportive care (the syndrome carries high mortality; plasma exchange has limited efficacy, and complement-directed therapy is used in select cases); rehydrate for prerenal AKI. Renal recovery is variable and may be incomplete in established TMA.Lesion-level management framework

Risk factors

Concurrent mitomycin C (dominant TMA driver)
Cumulative mitomycin/fluoropyrimidine exposure
Volume depletion from diarrhea/mucositis
DPD (DPYD) deficiency for severe systemic toxicity

Prevention

Recognize mitomycin as the dominant TMA driver and cap its cumulative dose
Hydration and prompt management of GI toxicity
Consider DPYD genotyping before fluoropyrimidine start

Anticancer mechanism· how it treats cancer

Fluoropyrimidine antimetabolite whose active metabolites (FdUMP, FUTP, FdUTP) inhibit thymidylate synthase and incorporate into RNA and DNA, blocking nucleotide synthesis. Catabolized predominantly by dihydropyrimidine dehydrogenase (DPD). Backbone of colorectal, gastric, pancreatic, breast and head and neck regimens.

§04

Clinical depth

Renal dose adjustment

No standard CrCl-based dose adjustment for IV 5-FU (catabolism is enzymatic via DPD, not renal); dose by toxicity and consider DPYD-genotype-guided reduction. In significant renal impairment, monitor closely but renal clearance is a minor pathway.

Dialyzability & ESKD dosing

5-FU has a very short half-life and is enzymatically catabolized; it is not managed by dialysis. Its catabolite fluoro-beta-alanine is renally excreted and can accumulate in renal failure but is not the toxic species.

Differential diagnosis

Chemo-associated TMA/HUS (Coombs-negative microangiopathic hemolysis, schistocytes, thrombocytopenia, normal-ish coagulation, often mitomycin-related) vs prerenal azotemia from diarrhea (volume-responsive, low FeNa) vs other causes of AKI. ADAMTS13 is usually not severely deficient, separating it from classic TTP.

Monitoring

CBC, LDH, haptoglobin and creatinine - rising LDH with thrombocytopenia signals TMA
Volume/diarrhea status each cycle
DPYD genotype or phenotype where available before fluoropyrimidine start

Key trials & series

Mitomycin-5-FU HUS literature (Jain Pathology 1987; Martinez Frances Med Clin 1997 35-patient TTP/HUS series)
Henricks Lancet Oncol 2018 - prospective DPYD genotype-guided fluoropyrimidine dosing safety study

Clinical pearls

Single-agent 5-FU is renally benign - when TMA appears, look hard at the mitomycin C in the regimen and its cumulative dose.
Fluoropyrimidine toxicity is enzymatic (DPD), not renal - DPYD genotyping, not CrCl, is the key safety screen.
Mitomycin/5-FU TMA can surface months in and is cumulative-dose related; persistent thrombocytopenia plus hemolysis should not be dismissed.

Where it strikes· nephron segments & injury signatures

Nephron segments

Vasculature / Endothelium

Glomerular & peritubular capillaries

Injury signatures

Thrombotic Microangiopathy Prerenal / Hemodynamic AKI

Beyond the kidney — non-renal toxicities· 4 organ systems

Class-level context for the major non-renal toxicities of the Pyrimidine analog class.

Gastrointestinal

Diarrhea, colitis, mucositis, perforation

Mucositis and diarrhea

Hepatic / Liver

Transaminitis, hepatitis, VOD/SOS

Transaminitis (methotrexate)

Hematologic

Cytopenias, thrombosis, TMA

Myelosuppression

Pulmonary

Pneumonitis, ILD, effusions, hypertension

Methotrexate / gemcitabine pneumonitis

§05

References

7 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

7 references · 1987–2018 · 1 since 2016

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· 2

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 · ModerateCapecitabine-Related Thrombotic Microangiopathy.Mateo FJP et al. · J Gastrointest Cancer 2024 · PMID 38175385Biopsy-confirmed renal thrombotic microangiopathy attributed to capecitabine (the oral prodrug of 5-fluorouracil) in an elderly woman, with recovery of renal function after drug withdrawal.CaseC · LimitedRapid tumor lysis syndrome in a patient with metastatic colon cancer as a complication of treatment with 5-fluorouracil/leucoverin and irinotecan.Oztop I et al. · Tumori 2004 · PMID 15656341Acute renal failure from tumor lysis syndrome occurring 72 hours after 5-fluorouracil/leucovorin plus irinotecan for metastatic colon cancer, a fatal renal complication of 5-FU-based chemotherapy.

FDA label — boxed warning & renal dosing· boxed warning

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

Boxed warning

WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY Increased Risk of Serious Adverse Reactions or Death in Patients with Complete DPD Deficiency Test patients for genetic variants of DPYD prior to initiating fluorouracil unless immediate treatment is necessary. Avoid use of fluorouracil in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency [see Warnings and Precautions (5.1)] WARNING: SERIOUS ADVERSE REACTIONS OR DEATH IN PATIENTS WITH COMPLETE DPD DEFICIENCY See full prescribing information for complete boxed warning Serious adverse reactions or death may occur in patients with complete DPD deficiency. Test patients for genetic variants of DPYD prior to initiating fluorouracil unless immediate treatment is necessary. Avoid use of fluorouracil in patients with certain homozygous or compound heterozygous DPYD variants that result in complete DPD deficiency. (2.1, 5.1)

What gets reported — FAERS

Everything below is FAERS — adverse events someone chose to report, about 76,954 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

Thrombotic Microangiopathycorroborated · ROR 4.09
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 5.9695% CI 5.50–6.46· 621 reports

Thrombotic Microangiopathy

ROR 4.0995% CI 3.58–4.66· 229 reports

Electrolyte Disturbance

ROR 3.8495% CI 3.69–4.00· 2,600 reports

SIADH / Hyponatremia

ROR 2.7395% CI 2.54–2.93· 796 reports

Acute Tubular Necrosis

ROR 2.4095% CI 1.94–2.96· 86 reports

Fanconi Syndrome

ROR 1.7195% CI 1.21–2.42· 32 reports

Hypertension

ROR 1.2395% CI 1.17–1.29· 1,730 reports

FAERS outcomes & reporting trend· 14.1% of reports w/ death · 40.1% w/ hospitalization

14.1%

Reported with a death outcome

10,859 of 76,954 reports

40.1%

Reported with hospitalization

30,821 of 76,954 reports

Reports per year

Yearly FAERS report volume · most recent year is partial.

FAERS adverse-event signal — all organ systems· 8 systems · 76,954 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 2.1295% CI 2.00–2.25· 1,171 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

Diarrhoea6,993Nausea5,003Vomiting3,999Abdominal Pain1,914Mucosal Inflammation1,806

Blood & lymphatic

Neutropenia5,175Thrombocytopenia2,967Febrile Neutropenia2,890Anaemia2,548Leukopenia1,619

General / constitutional

Fatigue3,228Pyrexia3,063Asthenia2,574

Metabolic & electrolyte

Decreased Appetite2,050Dehydration1,711

Respiratory

Dyspnoea2,041Pulmonary Embolism1,407

Nervous system

Neuropathy Peripheral3,378

Skin

Rash1,564

Immune / infection

Sepsis1,396

Guidelines & consensus· 14

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.

ADQIConventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupKidney Int 2026 · PMID 41881107Cisplatin is identified as a leading cytotoxic nephrotoxin; the workgroup details preventive measures (adequate isotonic hydration, correction of volume depletion, avoidance of concurrent nephrotoxins, attention to electrolyte/magnesium wasting) and management of cisplatin-associated AKI, with a research agenda for knowledge gaps.

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 5-Fluorouracil 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

Capecitabine

Xeloda · Pyrimidine analog (oral 5-FU)

Profile

Diarrhea-driven prerenal AKI; dose-adjust for CrCl.

PRETMA

Mild#1 · 100% phenotype match

Docetaxel

Taxotere · Taxane

Profile

Fluid retention; low direct renal toxicity.

PRECYSTTMA

Mild#2 · 73% phenotype match

Ruxolitinib

Jakafi · JAK1/2 inhibitor

Profile

Tumor lysis in myelofibrosis; renally adjusted.

PRELYTETMA

Mild#3 · 71% phenotype match

Trifluridine/tipiracil

Lonsurf · Oral fluoropyrimidine + TP inhibitor

Profile

Tipiracil is renally cleared; reduced GFR raises exposure and early severe neutropenia; dose-reduce in renal impairment.

PRE

Moderate#4 · 68% phenotype match

Ponatinib

Iclusig · BCR-ABL TKI

Profile

Vascular toxicity and hypertension.

HTNPRETMA

Moderate#5 · 68% phenotype match

Doxifluridine

Furtulon · Antimetabolite (oral 5-FU prodrug)

Profile

5'-DFUR prodrug; class-level TMA risk plus a real renal-clearance component warranting caution in renal impairment.

TMALYTEPRE

Moderate#6 · 67% phenotype match

Compare 5-Fluorouracil 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 Antimetabolites

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.

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 5-Fluorouracil’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 5-Fluorouracil; 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 132 clinical records among the 300 most-relevant of 363 PubMed matches, so counts are within-sample — bibliometric context, not an endorsement or a measure of clinical authority.