CYSTEINYL LEUKOTRIENES IN THE URINE OF PATIENTS WITH LIVER-DISEASES

The significance of,cysteinyl leukotrienes was investigated in patients with liver diseases by measurements of leukotriene E(4) and N-acetyl-leukotriene E(4) in urine. A marked increase of renal cysteinyl leukotriene excretion was observed in patients with cirrhosis without and with ascites, intrahepatic cholestasis, and obstructive jaundice as compared with healthy subjects (leukotriene E(4): means 82, 264, 221 and 142 versus 40 nmol/mol creatinine, respectively; N-acetyl-leukotriene E(4): means 25, 64, 61 and 47 versus 13 nmol/mol creatinine, respectively). The urinary concentration of leukotriene E(4) was positively correlated with the one of N-acetyl-leukotriene E(4) (r = 0.81, p < 0.001). In patients with cirrhosis, the excretion of cysteinyl leukotrienes was strongly increased in patients in Child-Turcotte stage C as compared with those in Child-Turcotte stages A and B. In patients with intrahepatic cholestasis and in those with obstructive jaundice, the excretion of leukotriene E(4) plus N-acetyl-leukotriene E(4) was positively correlated with total serum bilirubin. In patients with cirrhosis and in those with obstructive jaundice, the cysteinyl leukotrienes in urine were negatively correlated with creatinine clearance. The elevated renal excretion of cysteinyl leukotrienes decreased after biliary drainage in patients with obstructive jaundice. These data support the concept that increased urinary excretion of cysteinyl leukotrienes in patients with cirrhosis is due to a reduced functional liver mass and that in patients with cholestasis it is mainly due to an impaired elimination into the biliary tract that results in a diversion to renal excretion. The increased concentrations of biologically active cysteinyl leukotrienes may play an important role in the renal circulatory disturbance in patients with cirrhosis and obstructive jaundice.