CYSTEINYL LEUKOTRIENES IN THE URINE OF PATIENTS WITH LIVER-DISEASES

The significance of,cysteinyl leukotrienes was investigated in patient s with liver diseases by measurements of leukotriene E(4) and N-acetyl -leukotriene E(4) in urine. A marked increase of renal cysteinyl leuko triene excretion was observed in patients with cirrhosis without and w ith ascites, intrahepatic cholestasis, and obstructive jaundice as com pared 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, respectiv ely). The urinary concentration of leukotriene E(4) was positively cor related 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 compa red with those in Child-Turcotte stages A and B. In patients with intr ahepatic cholestasis and in those with obstructive jaundice, the excre tion 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 uri ne were negatively correlated with creatinine clearance. The elevated renal excretion of cysteinyl leukotrienes decreased after biliary drai nage in patients with obstructive jaundice. These data support the con cept that increased urinary excretion of cysteinyl leukotrienes in pat ients with cirrhosis is due to a reduced functional liver mass and tha t in patients with cholestasis it is mainly due to an impaired elimina tion into the biliary tract that results in a diversion to renal excre tion. The increased concentrations of biologically active cysteinyl le ukotrienes may play an important role in the renal circulatory disturb ance in patients with cirrhosis and obstructive jaundice.