Busulfan
Myleran · Alkylator
Conditioning-regimen TMA risk.
TMA
ModerateOpen →
Antimetabolite (oral 5-FU prodrug)
Tegafur-uracil (UFT)
UFT · UFT
Oral 5-FU prodrug (tegafur + uracil); kidney-sparing as a class, with rare fluoropyrimidine-associated thrombotic microangiopathy.
Severeestablished · approved 1984
Colorectal cancer (adjuvant and advanced, largely Japan/Europe)Gastric cancerHead and neck and other solid tumors (regional use)
Signature kidney injury
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
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeveritySevere
ReversibilityVariable
Evidence0 refs
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.
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.
Onset
Variable; TMA/HUS typically emerges after weeks to months of cumulative exposure.
Reversibility
Variable
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.
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
- Monitor CBC, smear for schistocytes, LDH, and creatinine during therapy
- Maintain hydration; correct electrolyte losses
- Caution combining with mitomycin C
- Dose with care in renal impairment given reduced 5-FU clearance
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. Conservatively framed.
Clinical depth
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
- Serum creatinine/eGFR
- Blood pressure
- Urinalysis for proteinuria/hematuria
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
- UFT is an oral 5-FU prodrug; the kidney concern is the rare fluoropyrimidine-class TMA/HUS, not routine tubular toxicity.
- 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.
Where it strikes
Nephron segments
Vasculature / Endothelium
Glomerular & peritubular capillaries
Glomerulus
Filtration barrier (podocytes + endothelium)
Injury signatures
Thrombotic MicroangiopathyElectrolyte WastingPrerenal / Hemodynamic AKI
Beyond the kidney
Class-level context for the major non-renal toxicities of antimetabolite (oral 5-fu prodrug)s.
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
Evidence
3 peer-reviewed references. Citation metadata via PubMed / NLM.
PMID[A case report of hemolytic uremic syndrome (HUS) induced by antineoplastic agents].Anai H et al. · Nihon Gan Chiryo Gakkai Shi 1990 · PMID 2120375Fatal HUS in a gastric cancer patient treated with a regimen including UFT and mitomycin C; supports rare fluoropyrimidine/combination-associated TMA-HUS as the renal signature.LandmarkConventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis 2021 · PMID 35190107Onconephrology review summarizing chemotherapy-associated AKI mechanisms including thrombotic microangiopathy and electrolyte disturbances relevant to the fluoropyrimidine class.LandmarkAcute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med 2017 · PMID 28467867Authoritative review of cancer-associated AKI, including drug-induced TMA and prerenal/electrolyte contributions framing UFT's class-level renal risk.
Related agents
Other agents sharing the same signature kidney injury.