Busulfan
Myleran · Alkylator
Conditioning-regimen TMA risk.
TMA
ModerateOpen →
Antimetabolite (oral 5-FU prodrug)
Carmofur (HCFU)
Mifurol · HCFU
Oral 5-FU prodrug used mainly in Japan; kidney-sparing as a class, better known for leukoencephalopathy than nephrotoxicity.
Moderateestablished · approved 1981
Colorectal cancer (adjuvant/advanced, primarily Japan)Gastric and breast cancer (regional use)
Signature kidney injury
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)
Toxicity fingerprint
Tap a signature to trace where it strikes the nephron.
Incidence not quantified
SeverityModerate
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
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).
Onset
Variable; class-level TMA after cumulative exposure.
Reversibility
Variable
Anticancer mechanism
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.
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.
Risk factors
- Concurrent TMA-associated agents
- Renal impairment
- Volume depletion from GI losses
- Higher cumulative fluoropyrimidine exposure
Prevention
- Monitor renal function and electrolytes
- Maintain hydration; replace GI losses
- Monitor CBC/smear and LDH for TMA on prolonged therapy
- Remain alert to the more characteristic leukoencephalopathy
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. Framed conservatively.
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
- Serum creatinine/eGFR
- Electrolytes
- 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
- Carmofur is a lipophilic oral 5-FU prodrug; its hallmark serious adverse effect is leukoencephalopathy, not kidney injury.
- 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.
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[Combination effects of CDDP, ACR and HCFU on progressive urothelial tumors].Ueda K et al. · Gan To Kagaku Ryoho 1985 · PMID 3859251Clinical use of carmofur (HCFU) in combination chemotherapy; reports no severe nephrotoxicity, consistent with the drug's kidney-sparing, class-level renal profile.LandmarkConventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis 2021 · PMID 35190107Onconephrology review supporting class-level fluoropyrimidine renal framing (rare TMA, electrolyte disturbance).LandmarkAcute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med 2017 · PMID 28467867Cancer-AKI review covering drug-induced TMA and prerenal/electrolyte mechanisms underpinning carmofur's conservative renal profile.
Related agents
Other agents sharing the same signature kidney injury.