Treatment of Type I Hepatorenal Syndrome (HRS) With Pentoxyfylline

Each hospitalized subject will undergo pre-dosing screening with review of his or her
history and physical exam from the day of enrollment and safety assessment to ensure no
contraindication to use of PTX. Type I HRS will be defined according to the criteria put
forth by the American Association for the Study of Liver Disease as (1) cirrhosis with
ascites; (2) serum creatinine greater than 1.5 mg/dL; (3) no improvement of serum creatinine
(decrease to a level of 1.5 mg/dL or less) after at least two days with diuretic withdrawal
and volume expansion with albumin; (4) absence of shock; (5) no current or recent treatment
with nephrotoxic drugs; and (6) absence of parenchymal kidney disease as indicated by
proteinuria >500 mg/day, microhematuria (>50 red blood cells per high power field), and/or
abnormal renal ultrasonography. Baseline testing will be obtained from hospitalization
records, including but not limited to chemistry panel, liver function testing, urinalysis,
urine electrolytes, coagulation studies, blood cultures, chest x-ray, diagnostic
paracentesis, abdominal ultrasound with Doppler.

Subjects will take either placebo three times a day or pentoxyfylline 400mg three times a
day or 400mg twice a day for eGFR 10-50 and 400mg once a day for eGFR <10 for 90 days in
addition to standard AMO therapy. Treatment will be continued for 14 days unless a study
endpoint has been reached at which time either PTX or placebo will be stopped

Inclusion Criteria:

- Hospitalized patients with acute or chronic liver disease

- Type I HRS

- Aged greater than or equal to 18

- Non-pregnant

Exclusion Criteria:

- Allergy or hypersensitivity to PTX or intolerance to methylxanthines (e.g. caffeine,
theophylline)

- Concurrent use of nephrotoxic drugs

- Age less than 18

- Pregnancy

- Uncontrolled bacterial infection

- Renal parenchymal disease (e.g. acute tubular necrosis, glomerular disease,
interstitial nephritis and urinary obstruction)

- Shock

- TNF alpha antagonist use

- Subject is institutionalized or a prisoner

- Recent cerebral or retinal hemorrhage (contraindication to PTX)

- Severe or poorly controlled cardiovascular disease as determined by the principal
investigator to hinder the ability to adhere to study protocols