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World J Hepatol. Jan 28, 2017; 9(3): 131-138
Published online Jan 28, 2017. doi: 10.4254/wjh.v9.i3.131
Cockcroft-Gault revisited: New de-liver-ance on recommendations for use in cirrhosis
Gianni B Scappaticci, Randolph E Regal
Gianni B Scappaticci, Department of Pharmacy Services, University of Michigan Health System and College of Pharmacy, Ann Arbor, MI 48109-2054, United States
Randolph E Regal, Department of Pharmacy Services, Adult Internal Medicine/Gastroenterology, University of Michigan Health System and College of Pharmacy, Ann Arbor, MI 48109-2054, United States
Author contributions: Scappaticci GB performed the majority of the writing, prepared the figures and tables; Regal RE designed the outline, coordinated the writing of the paper, provided input and feedback, and contributed to writing.
Conflict-of-interest statement: Both authors do not have any conflicts to disclose regarding the content of this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Gianni B Scappaticci, PharmD, PGY1 Pharmacy Resident/Adjunct Clinical Instructor, Department of Pharmacy Services, University of Michigan Health System and College of Pharmacy, 1111 E. Catherine Street, Ann Arbor, MI 48109-2054, United States. gbscapp@med.umich.edu
Telephone: +1-734-7647007 Fax: +1-734-6152314
Received: August 21, 2016
Peer-review started: August 23, 2016
First decision: October 28, 2016
Revised: November 11, 2016
Accepted: December 13, 2016
Article in press: December 14, 2016
Published online: January 28, 2017
Processing time: 154 Days and 2 Hours
Abstract

The Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function among health care professionals. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of the many variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying pathophysiology of the disease contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population. We reviewed the original CG trial from 1976 along with data surrounding clinician specific alterations to the CG equation that followed through time. These alterations included different formulas for body weight in obese patients and the “rounding up” approach in patients with low SCr. Additionally, we described the pathophysiology and hemodynamic changes that occur in cirrhosis; and reviewed several studies that attempted to estimate renal function in this population. The evidence we reviewed regarding the most accurate manipulation of the original CG equation to estimate creatinine clearance (CrCl) was inconclusive. Unfortunately, the homogeneity of the patient population in the original CG trial limited its external validity. Elimination of body weight in the CG equation actually produced the estimate closest to the measure CrCl. Furthermore, “rounding up” of SCr values often underestimated CrCl. This approach could lead to suboptimal dosing of drug therapies in patients with low SCr. In cirrhotic patients, utilization of SCr based methods overestimated true renal function by about 50% in the literature we reviewed.

Keywords: Cockcroft-Gault; Cirrhosis; Renal function; Pharmacokinetics; Creatinine clearance

Core tip: For many health care professionals in the United States, the Cockcroft-Gault (CG) equation has become perhaps the most popular practical approach for estimating renal function. Despite its widespread use, clinicians often overlook not only the limitations of the original serum creatinine (SCr) based equation, but also may not appreciate the validity of variations used to compensate for these limitations. For cirrhotic patients in particular, the underlying disease pathophysiology contributes to a falsely low SCr, thereby overestimating renal function with use of the CG equation in this population.