Is kidney injury from Carmofur (HCFU) reversible?

Variable. Typical onset: Variable; class-level TMA after cumulative exposure..

How should kidney function be monitored during Carmofur (HCFU) therapy?

CBC with peripheral smear if TMA suspected; LDH; Neurologic status (leukoencephalopathy surveillance).

Who is at higher risk of kidney injury from Carmofur (HCFU)?

Concurrent TMA-associated agents; Renal impairment; Volume depletion from GI losses; Higher cumulative fluoropyrimidine exposure.

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Printable monograph

Antimetabolite (oral 5-FU prodrug)

Carmofur (HCFU)

Mifurol · HCFU

Antimetabolite (oral 5-FU prodrug) · approved 1981 · 3 citations

Aging evidence· through 2021

Fairly sourced5/9 · 4 signals

Not met: 3 citations
Not met: 12+ references
Met: Accrued over 10+ years (span: 36y)
Met: Beyond single case reports
Met: High-impact journal
Met: Landmark reference
Not met: Current through 2021
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.

Oral 5-FU prodrug used mainly in Japan; kidney-sparing as a class, better known for leukoencephalopathy than nephrotoxicity.

Moderateestablished

Colorectal cancer (adjuvant/advanced, primarily Japan)Gastric and breast cancer (regional use)

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Signature kidney injury

Signature lesion

Thrombotic Microangiopathy

No established drug-specific renal incidence. Renal risk is class-level (rare fluoropyrimidine TMA/HUS). Carmofur's characteristic serious toxicity is leukoencephalopathy, not nephrotoxicity.Source: Gupta et al., Adv Chronic Kidney Dis 2021 (class-level)

Onset & rechallenge

Time to injuryVariable / unpredictable

Variable onset, with class-level TMA arising after cumulative exposure.

Distilled from: “Variable; class-level TMA after cumulative exposure.”

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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.
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).
Prerenal / Hemodynamic AKISecondaryqualitative — no citable incidence
Renal hypoperfusion from capillary leak and cytokine storm — IL-2 and CAR-T cytokine release syndrome.

Toxicity fingerprint

Tap a signature to trace where it strikes the nephron.

Incidence not quantified

SeverityModerate

ReversibilityVariable

Evidence3 citations

Nephron map

GlomerulusFiltration barrier (podocytes + endothelium)

Vasculature / EndotheliumGlomerular & peritubular capillaries

Distal Tubule / Collecting Duct

Thrombotic Microangiopathy

Endothelial injury with microvascular thrombi, hemolysis and thrombocytopenia — gemcitabine, mitomycin C, anti-VEGF.

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Kidney injury

Mechanism of kidney injury

Shares the fluoropyrimidine-class potential for endothelial injury and rare thrombotic microangiopathy via 5-FU. Direct tubular nephrotoxicity is not a recognized feature; most renal events in treated patients reflect prerenal/electrolyte disturbance from GI toxicity rather than a carmofur-specific renal lesion.

Clinical presentation

Generally renally well tolerated. Rare class-level TMA/HUS would present with microangiopathic hemolytic anemia, thrombocytopenia and rising creatinine. The signature severe carmofur toxicity is delayed leukoencephalopathy (neurologic, not renal).

Management

For suspected fluoropyrimidine-associated TMA, discontinue and provide supportive care with nephrology/hematology input (BP control, transfusion, dialysis for severe AKI). Treat prerenal AKI with volume and electrolyte correction.Lesion-level management framework

Risk factors

Concurrent TMA-associated agents
Renal impairment
Volume depletion from GI losses
Higher cumulative fluoropyrimidine exposure

Anticancer mechanism· how it treats cancer

1-Hexylcarbamoyl-5-fluorouracil (HCFU) is a lipophilic oral prodrug that releases 5-fluorouracil, whose active metabolites inhibit thymidylate synthase and incorporate into RNA/DNA to block nucleotide and nucleic-acid synthesis. Its lipophilicity favors sustained 5-FU exposure.

Note · Renal data are very thin and class-level; the available carmofur literature emphasizes oncologic use and (separately) neurotoxicity, with no robust kidney-specific signal.

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Clinical depth

Renal dose adjustment

No validated renal nomogram; use caution and consider reduction in significant renal impairment given renal elimination of 5-FU metabolites, per regional labeling.

Dialyzability & ESKD dosing

Not well characterized; dialysis is supportive for AKI rather than for drug removal.

Differential diagnosis

Distinguish class-level TMA from other TMA causes, prerenal AKI from GI losses, and obstructive uropathy; do not attribute neurologic decline (leukoencephalopathy) to a renal cause.

Monitoring

CBC with peripheral smear if TMA suspected
LDH
Neurologic status (leukoencephalopathy surveillance)

Key trials & series

No nephrotoxicity-endpoint trial; renal risk is inferred from fluoropyrimidine-class onconephrology reviews.

Clinical pearls

Renal risk is class-level and rare — think fluoropyrimidine TMA only with supporting hematologic signs.
GI-loss-driven prerenal azotemia is the more common, reversible renal issue.

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

Class-level context for the major non-renal toxicities of the Antimetabolite (oral 5-FU prodrug) 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

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References

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

Evidence accrual

3 references · 1985–2021 · 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.

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 Carmofur (HCFU) 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

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#1 · 100% phenotype match

Tegafur-uracil (UFT)

UFT · Antimetabolite (oral 5-FU prodrug)

Profile

Oral tegafur+uracil; rare fluoropyrimidine-class TMA/HUS (often with mitomycin C), otherwise kidney-sparing.

TMALYTEPRE

Severe#2 · 94% phenotype match

Ruxolitinib

Jakafi · JAK1/2 inhibitor

Profile

Tumor lysis in myelofibrosis; renally adjusted.

PRELYTETMA

Mild#3 · 69% phenotype match

Decitabine

Dacogen · Hypomethylating agent

Profile

Tumor lysis in MDS/AML.

XTALPRELYTE

Mild#4 · 67% phenotype match

Capecitabine

Xeloda · Pyrimidine analog (oral 5-FU)

Profile

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

PRETMA

Mild#5 · 66% phenotype match

5-Fluorouracil

Adrucil · Pyrimidine analog

Profile

Rare TMA, esp. with mitomycin; mostly renally safe.

TMAPRE

Mild#6 · 66% phenotype match

Compare Carmofur (HCFU) 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.