Study to Evaluate if the Drug Vasopressin Protects the Kidneys for Patients Undergoing Liver Transplant

Renal failure is a common complication of liver disease. Hepatorenal syndrome is caused by a
dysfunctional global circulation in the setting of liver disease: Increased flow to the
mesenteric circulation is a contributor to decreased blood flow to the kidneys (1). Renal
failure often worsens in the perioperative period of liver transplantation since the kidneys
are further stressed by reduced flow due to inferior venacava occlusion, decreased blood flow
to the kidneys from anesthetics, as well as hypotension from volume shifts, such as when
large volumes of ascites are removed. Renal failure is a cause of major morbidity and
mortality in patients undergoing liver transplantation.

Vasopressin is a logical choice of therapy in this context as the effects of the drug work to
particularly increase renal blood flow and glomerular filtration rate due to the location of
specific vasopressin receptors within the renal vasculature. It has been suggested that the
use of splanchnic (and systemic) vasoconstrictors such as terlipressin (a vasopressin analog)
or alpha-1-adrenoceptor agonists (midodrine or noradrenaline) may improve renal function in
patients with type 1 Hepatorenal Syndrome.

Six studies (with only one randomized study in a small series of patients) have shown that
terlipressin improves renal function in these patients (2-7). This drug is available in
Europe, but not in the United States. However, while anesthesiologists commonly use
vasopressin during liver transplantation in the setting of hepatorenal syndrome or
vasodilatory shock, the validity of this practice for its effects on renal function and
outcomes has not been rigorously studied (8-10). Therefore, the purpose of this study is to
evaluate the effects of low-dose vasopressin on intraoperative and perioperative renal
function in liver transplant patients.

This study will be a randomized, double-blind controlled trial performed in adult liver
transplant patients coming to surgery for chronic liver disease; the major end-points of
analyses are renal function tests in the perioperative period.

Inclusion Criteria:

- > 18 years of age

- undergoing liver transplant

- ability to provide informed consent. If patient is unable to give informed consent
i.e. hepatic encephalopathy, consent may be obtained from the patient's legally
authorized representative

Exclusion Criteria:

- < 18 years of age

- renal failure