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PHARMACOKINETICS

Estimation of Creatinine Clearance in End-Stage Liver Disease

Professor, Department of Pharmacy Practice & Science, College of Pharmacy, University of Arizona

Brian L Erstad, PharmD

Associate Professor, Department of Pharmacy Practice & Science, College of Pharmacy, University of Arizona, Tucson, AZ

Paul Z Nakazato, MD

at time of writing, Associate Professor, Department of Surgery, College of Medicine, University of Arizona; now, General Surgery (private practice), Tucson

Jeffrey F Barletta, PharmD

at time of writing, Critical Care Specialty Pharmacy Resident, University of Arizona; now, Clinical Specialist—Critical Care, Department of Pharmacy Services, Spectrum Health, Grand Rapids, MI

Kathryn R Matthias, PharmD

at time of writing, PharmD Student, College of Pharmacy, University of Arizona; now, Pharmacy Practice Resident, College of Pharmacy, University of Arizona

Todd S Krueger, PharmD

at time of writing, Infectious Diseases Pharmacotherapy Fellow, University of Arizona; now, Clinical Science Liaison, Cubist Pharmaceuticals, Lexington, MAy

Reprints: Dr. Nix, University of Arizona, College of Pharmacy, 1703 E. Mabel St., PO Box 210207, Tucson, AZ 85721-0207, fax 520/626-7355, nix{at}pharmacy.arizona.edu

BACKGROUND: Estimation of renal function in patients with end-stage liver disease (ESLD) is complicated by several factors.

OBJECTIVE: To develop a practical and relatively inexpensive method for estimating creatinine production and clearance in patients with ESLD.

METHODS: Serum creatinine concentrations and urinary excretion of creatinine were measured in 27 patients with moderate-to-severe liver disease with the goal of developing equations to predict creatinine clearance from serum creatinine. Subjects were studied during an initial evaluation for a liver transplant program. Two 24 hour urine specimens were collected along with 3 serum samples over a 2 day evaluation period. Serum and urine creatinine concentrations were determined using both a modified Jaffé (autoanalyzer) method and an HPLC method. The data were analyzed using nonlinear mixed-effects modeling.

RESULTS: Considering both statistical criteria and physiological conventions through allometric scaling theory, creatinine clearance (mL/min) in males can be estimated as (80/serum creatinine) x (actual body weight/70)^0.75. For females, the same equation is valid, but the result is multiplied by 0.661. A simplified equation without the exponent is presented, along with equations that are appropriate when an HPLC assay is used for greater specificity.

CONCLUSIONS: These equations offer potential for improved estimation of creatinine clearance in patients with liver impairment; however, they need further validation using an independent group of subjects.

Key Words: assay, creatinine clearance, liver disease, renal function.

Published Online, May 2, 2006. www.theannals.com, DOI 10.1345/aph.1G594