Plasma levels of endothelin-1 in patients with the hepatorenal syndrome after successful liver transplantation

The hepatorenal syndrome (HRS) is characterized by renal vasoconstriction l eading to deterioration of renal function in patients with liver disease. A possible role of endothelin-l (ET-1) in the pathogenesis of HRS has been s uggested, but a correlation between ET-1 plasma levels and the development of HRS as well as the recovery from HRS following OLT has not bl:en shown y et. We performed longitudinal measurements of ET-1 plasma levels in four gr oups of patients, 5 patients with HRS before and after orthotopic liver tra nsplantation (OLT), 10 patients without HRS undergoing OLT, 20 patients wit h chronic renal failure but without liver disease, and 12 healthy controls. Before OLT, plasma levels of ET-1 were higher in patients with HRS (19.5 /- 8.6 ng/l, P < 0.001; n = 5) compared to patients without HRS (4.9 +/- 1. 1 ng/l; n = 10), normals (1.2 +/- 0.18 ng/l; n = 12), and patients with chr onic renal failure (2.4 +/- 0.4 ng/l; n = 20). Patients with HRS compared t o patients without HRS had higher levels for creatinine (2.42 +/- 0.6 vs. 0 .89 +/- 0.05 mg/dl, P < 0.05), creatinine clearance (107 +/- 9 ml/min vs. 4 4.6 +/- 5.5 ml/min, P < 0.001), and bilirubin (11.4 +/- 3.8 vs. 3.7 +/- 1 m g/dl, P < 0.05) before OLT. Within one week after OLT, there was a rapid de crease in ET-1 levels in patients with HRS while creatinine and bilirubin l evels decreased slower. Regression analysis revealed a weak correlation bet ween serum creatinine and ET-1 (r = 0.192, P = 0.04) and a significant corr elation between serum bilirubin and ET-1 (r = 0.395, P < 0.001). The means of the ET-1 levels decreases rapidly with improvement of liver function aft er OLT. Levels of ET-I correlate with excretory liver function assessed by bilirubin. The fall in ET-1 levels preceding improvement of renal function further strengthens the concept of ET-1 being a causative factor in HRS.