Increased excretion of endogenous urinary leukotriene E4 in extrahepatic cholestasis

The cysteinyl leukotrienes LTC4, LTD4 and LTE4 are potent lipid mediators eliminated from the blood circulation mainly due to uptake by the liver and the kidneys. In man hepatobiliary elimination of cysteinyl leukotrienes predominates over renal excretion. In the present study, the urine from patients with extrahepatic cholestasis (n = 25) and age- and sex-matched healthy control subjects (n = 25) was analyzed for endogenous LTE4, the predominant metabolite of LTC4 excreted into urine. LTE4 was separated by reversed-phase high-performance liquid chromatography and subsequently quantified by enzyme immunoassay. Healthy subjects excreted a median concentration of 14 nmol LTE4/mol creatinine (range 5-24 nmol/mol creatinine). Its median concentration increased significantly to more than 5-fold higher levels to 74 nmol LTE4/mol creatinine (range 52-93 nmol/mol creatinine) in patients with extrahepatic cholestasis (P < 0.01). These results indicate that extrahepatic cholestasis leads to a compensatory diversion of cysteinyl leukotriene elimination to the kidney with subsequent increased excretion of LTE4 into urine.