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Antimetabolite (oral 5-FU prodrug)

Doxifluridine

Furtulon · 5dFUR

Antimetabolite (oral 5-FU prodrug) · approved 1987 · 4 references

Oral 5-FU prodrug (5'-deoxy-5-fluorouridine) with a measurable renal clearance component; kidney risk is conservative and class-level.

Signature injury
Thrombotic Microangiopathy
Severity
Moderate
Reversibility
Variable
Onset
Variable; class-level TMA typically after prolonged cumulative exposure.

Signature kidney injury & incidence

Thrombotic Microangiopathy.

No drug-specific nephrotoxicity incidence is established. Renal risk is inferred at the fluoropyrimidine-class level (rare TMA/HUS); direct doxifluridine renal injury reports are sparse.

Source: Gupta et al., Adv Chronic Kidney Dis 2021 (class-level)

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) — Class-level TMA typically after prolonged cumulative exposure.

Mechanism of kidney injury

As a 5-FU prodrug, doxifluridine carries the fluoropyrimidine-class potential for endothelial injury and rare thrombotic microangiopathy. Pharmacokinetic data show renal excretion is a major but not dominant elimination route (Schaaf 1988: renal clearance 0.32 l/min against nonrenal 0.60 l/min at the lower dose, and 0.29 against 0.37 l/min after doubling — the renal share rises as the saturable nonrenal pathway is exceeded), so reduced kidney function could increase parent-drug and 5-FU exposure and the risk of systemic toxicity. Most renal events are likely prerenal/electrolyte-related from chemotherapy GI toxicity rather than direct tubular injury.

Clinical presentation

Generally renally well tolerated. If TMA/HUS occurs (class effect): microangiopathic hemolytic anemia, thrombocytopenia, rising creatinine, hypertension. Volume depletion from diarrhea/vomiting can cause prerenal azotemia.

Management

For suspected fluoropyrimidine-associated TMA, stop the drug and provide supportive care (blood pressure control, transfusion, renal support/dialysis as needed) with nephrology/hematology input. Manage prerenal AKI with volume resuscitation and electrolyte correction.

Risk factors

  • Renal impairment (reduced clearance of parent drug and 5-FU)
  • Concurrent TMA-associated agents (e.g., mitomycin C)
  • Volume depletion from GI toxicity
  • Higher cumulative fluoropyrimidine exposure

Prevention

  • Use caution in renal impairment given the renal clearance component

Renal dose adjustment

No validated renal nomogram. Given a documented renal clearance component for doxifluridine and renal elimination of 5-FU metabolites, consider caution/dose reduction in significant renal impairment per regional labeling.

Dialyzability & ESKD dosing

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

Differential diagnosis

Separate class-level TMA from other TMA etiologies, prerenal AKI from GI losses, and obstructive uropathy from underlying malignancy.

Monitoring

  • CBC with peripheral smear if TMA suspected
  • LDH

Key trials & series

  • No nephrotoxicity-endpoint trial. Pharmacokinetic study (Schaaf 1988, PMID 2974418) characterizes renal vs nonrenal clearance, underpinning renal-impairment caution.

Clinical pearls

  • PK data show a real renal clearance component — do not assume the kidney is irrelevant in renal impairment.
  • Renal toxicity is class-level and rare; reserve TMA workup for the right hematologic clues.

Anticancer mechanism

5'-Deoxy-5-fluorouridine is a prodrug converted to 5-fluorouracil, predominantly by pyrimidine nucleoside phosphorylase (thymidine phosphorylase), which is often elevated in tumor tissue. The liberated 5-FU is metabolized to FdUMP and FUTP, inhibiting thymidylate synthase and disrupting RNA/DNA synthesis.

Note

Renal data are thin and class-level, with no robust doxifluridine-specific nephrotoxicity literature. PK evidence (Schaaf 1988) is the basis for the renal-clearance caution.

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

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

  1. 1.Pharmacology of 5'-deoxy-5-fluorouridine in patients with resistant ovarian cancer.de Bruijn EA, van Oosterom AT, Tjaden UR, Reeuwijk HJ, Pinedo HM · Cancer Res · 1985 · PMID 2932219
  2. 2.The pharmacokinetics of doxifluridine and 5-fluorouracil after single intravenous infusions of doxifluridine to patients with colorectal cancer.Schaaf LJ et al. · Eur J Clin Pharmacol · 1988 · PMID 2974418
  3. 3.Conventional Chemotherapy Nephrotoxicity.Gupta S et al. · Adv Chronic Kidney Dis · 2021 · PMID 35190107
  4. 4.Acute Kidney Injury in Patients with Cancer.Rosner MH et al. · N Engl J Med · 2017 · PMID 28467867
Educational monograph from NephTox (nephtox.com). Not medical advice — verify against current guidelines before any clinical decision.