Doxifluridine

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.

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.

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.Lesion-level management framework

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.

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

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