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Antimetabolite (oral 5-FU prodrug)

Tegafur-uracil (UFT)

UFT · UFT

Antimetabolite (oral 5-FU prodrug) · approved 1984 · 3 references

Oral 5-FU prodrug (tegafur + uracil); kidney-sparing as a class, with rare fluoropyrimidine-associated thrombotic microangiopathy.

Signature injury
Thrombotic Microangiopathy
Severity
Severe
Reversibility
Variable
Onset
Variable; TMA/HUS typically emerges after weeks to months of cumulative exposure.

Signature kidney injury & incidence

Thrombotic Microangiopathy.

Direct renal injury from UFT is rare and largely class-level. Fluoropyrimidine-associated thrombotic microangiopathy / hemolytic-uremic syndrome is a rare, mostly case-report-level event, frequently in combination regimens (e.g., with mitomycin C). No reliable drug-specific incidence rate is established.

Source: Anai et al., case report 1990 (HUS with UFT + mitomycin C); not quantified

Reported injury signatures: Thrombotic Microangiopathy, Electrolyte Disturbance, Prerenal / Hemodynamic AKI.

Renal toxicity profile

  1. Thrombotic MicroangiopathyPrimary
  2. Electrolyte DisturbanceSecondary
  3. Prerenal / Hemodynamic AKISecondary

Onset timing & rechallenge

Delayed (>6 weeks / cumulative) — TMA/HUS after weeks to months of cumulative exposure.

Mechanism of kidney injury

Fluoropyrimidine-class endothelial injury is the proposed mechanism for the rare thrombotic microangiopathy/HUS, producing microvascular platelet-fibrin thrombi, mechanical hemolysis, thrombocytopenia and acute kidney injury; risk is amplified when co-administered with mitomycin C, a recognized TMA-associated agent. Most renal events in UFT-treated patients reflect this microvascular pathway or prerenal/electrolyte disturbances from chemotherapy-related GI losses rather than direct tubular toxicity.

Clinical presentation

When TMA/HUS occurs: microangiopathic hemolytic anemia with schistocytes, thrombocytopenia, rising creatinine, hypertension, edema, and sometimes hematuria/proteinuria. Otherwise UFT is generally renally well tolerated.

Management

Discontinue the offending fluoropyrimidine (and any co-administered mitomycin C) if TMA/HUS is suspected. Provide supportive care: blood pressure control, transfusion as needed, and renal support including dialysis for severe AKI. Hematology/nephrology co-management; plasma exchange has been used though evidence in drug-associated TMA is limited.

Risk factors

  • Concurrent mitomycin C or other TMA-associated agents
  • Higher cumulative fluoropyrimidine exposure
  • Pre-existing renal impairment
  • Volume depletion from chemotherapy-related GI losses

Prevention

  • Caution combining with mitomycin C
  • Dose with care in renal impairment given reduced 5-FU clearance

Renal dose adjustment

No universally validated renal dosing nomogram. Because 5-FU and metabolites have a renal elimination component, use caution and consider dose reduction in significant renal impairment; follow regional product labeling.

Dialyzability & ESKD dosing

Not well characterized for the tegafur/uracil combination; dialysis is used to support AKI rather than to remove drug.

Differential diagnosis

Distinguish drug-associated TMA from other TMA causes (mitomycin C, gemcitabine, complement-mediated/atypical HUS, malignancy-associated TMA), from prerenal AKI due to GI losses, and from tumor-related obstructive uropathy.

Monitoring

  • CBC with peripheral smear (schistocytes)
  • LDH, haptoglobin, bilirubin
  • Blood pressure
  • Urinalysis for proteinuria/hematuria
  • Serum creatinine during therapy

Key trials & series

  • No nephrotoxicity-endpoint trial; UFT efficacy is established in colorectal/gastric adjuvant and advanced-disease studies. Renal signal derives from case reports and class-level reviews.

Clinical pearls

  • Co-administered mitomycin C markedly raises TMA suspicion — review the full regimen.
  • New anemia + thrombocytopenia + rising creatinine on a fluoropyrimidine should prompt a schistocyte smear and LDH.

Anticancer mechanism

Oral combination of tegafur (a prodrug bioactivated to 5-fluorouracil) and uracil in a 1:4 molar ratio. Uracil competitively inhibits dihydropyrimidine dehydrogenase, raising and sustaining intratumoral 5-FU concentrations. 5-FU's active metabolites (FdUMP, FUTP) inhibit thymidylate synthase and are incorporated into RNA/DNA, impairing nucleotide synthesis.

Note

Renal data are thin and largely class-level; the best-documented UFT-related renal event is a fatal HUS case in a multi-agent regimen that included mitomycin C, so attribution to UFT alone is uncertain.

Guidelines & consensus

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.

  • ADQI (2026) — Conventional cytotoxic chemotherapy-associated nephrotoxicity: consensus report of the 34th Acute Disease Quality Initiative (ADQI) WorkgroupCisplatin 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.Kidney Int · PMID 41881107
  • ADQI (2026) — The nephrotoxic effects of anti-cancer therapies: consensus report of the 34th Acute Disease Quality Initiative workgroupProvides 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.Nat Rev Nephrol · PMID 41361704
  • SIRM (2022) — SIRM-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)Recommends 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.Radiol Med · PMID 35303246
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancerIdentifies 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.Kidney Int · PMID 33126977
  • KDIGO (2020) — KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantationAddresses 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.Kidney Int · PMID 33276867
  • ADDIKD (2025) — Integrating International Consensus Guidelines for Anticancer Drug Dosing in Kidney Dysfunction (ADDIKD) into everyday practiceProvides 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.EClinicalMedicine · PMID 40290844
  • ADDIKD (2025) — Aligning kidney function assessment in patients with cancer to global practices in internal medicineThree 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.EClinicalMedicine · PMID 40290845
  • ADDIKD (2025) — A methodology for determining dosing recommendations for anticancer drugs in patients with reduced kidney functionEstablishes 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.EClinicalMedicine · PMID 40290846
  • KDIGO (2013) — Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (Part 1)Defines/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.Crit Care · PMID 23394211
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease: known knowns and known unknownsEvaluate 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.Kidney Int · PMID 38519239
  • KDIGO (2021) — Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular DiseasesProvides 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.Kidney Int · PMID 34556300
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of ANCA-Associated VasculitisUpdates 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.Kidney Int · PMID 38388147
  • KDIGO (2024) — Executive summary of the KDIGO 2024 Clinical Practice Guideline for the Management of Lupus NephritisUpdates 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.Kidney Int · PMID 38182299
  • KDIGO (2025) — Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV)Encourages 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.Kidney Int · PMID 40975525

References

3 peer-reviewed references. Citation metadata via PubMed / NLM.

  1. 1.[A case report of hemolytic uremic syndrome (HUS) induced by antineoplastic agents].Anai H et al. · Nihon Gan Chiryo Gakkai Shi · 1990 · PMID 2120375
  2. 2.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107
  3. 3.Acute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med · 2017 · PMID 28467867

Case reports & series (1)

The weakest rung of clinical evidence — single-patient and small-series reports, strongest first. Each carries a heuristic strength grade (A Strong / B Moderate / C Limited) inferred from its abstract and journal, not a formal appraisal. Weigh well below the primary references above.

  1. C1.[C · Limited][A Case Report of a Patient Over 90 Years of Age with Liver Metastasis after Sigmoid Colectomy Controlled by a Combination Oral UFT/LV Chemotherapy Regimen].Owada Y et al. · Gan To Kagaku Ryoho · 2019 · PMID 32156861
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.