title: Single-dose gentamicin clearance is a predictor of creatinine clearance in spinal man.
abstract: To identify a radionuclide-free, SCI (spinal cord injury) population-specific method for estimating renal function utilizing the total body clearance of gentamicin as a measure of creatinine clearance (CL(cr)) and glomerular filtration rate (GFR). To incorporate SCI population-specific patient variables into a predictive model for estimating CLcr and GFR. A retrolective study of gentamicin clearance as a measure of GFR in patients with SCI. Each patient had received a single, intravenous dose of gentamicin. Simultaneously, a 24-hour creatinine clearance (CL(cr-24)) was obtained. Experimentally measured total body clearance of a single intravenous administration of gentamicin (CL(gent-iv)) was estimated from PK analyses of gentamicin disposition in patients with SCI. Comparisons were made between CL(gent-iv) and predictors of GFR derived from a SCI population-specific nomogram (SCI-psn), the method of Cockcroft and Gault (C-G), CL(cr-24), and a multiplicative statistical model. A multiplicative model, calculated gentamicin clearance (CL(gent-calc)), that incorporates SCI population-specific characteristics to predict CL(cr-24) and GFR was derived from a multivariate nonlinear regression analysis, and the strengths of association between CL(gent-iv) and CL(gent-calc), and estimates of GFR derived from the method of C-G, SCI-psn, and CL(cr-24) were tested. The best predictive performance was demonstrated for CL(gent-iv) and the multiplicative model, CL(gent-calc), when tested against CL(cr-24) or the SCI-psn, supporting our premise that CL(gent-iv) can be used to estimate GFR in SCI. CL(gent-iv) and CL(gent-calc) outperformed CL(cr-24), the method of C-G, and the SCI-psn as predictors of GFR. The multiplicative model produced estimates of CL(gent-iv) which were more precise and less biased than CL(cr-24), the standard radiation-free predictor of GFR in patients with SCI, the SCI-psn, and the C-G equation. In this preliminary study, the clearance of gentamicin administered intravenously, CL(gent-iv), correlated highly with simultaneously measured CL(cr-24). CL(gent-iv) and our predictive model, CL(gent-calc), are more precise and less biased predictors of GFR in SCI than CL(cr-24). CL(gent-iv) and CL(gent-calc) seem to be clinically useful alternatives to CL(cr-24), the method of C-G, and the SCI-psn.
authors.affiliation: Department of Medicine, Los Angeles County, Harbor-UCLA Medical Center & Los Angeles Biomedical Research Institute, Torrance, CA, USA.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Segal
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Gilman
authors.forename: John F
authors.initials: JF
authors.lastname: Thompson
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood / Q000652:urine; D005839:Gentamicins / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015233:Models, Statistical; D015999:Multivariate Analysis; D049451:Nomograms; D012044:Regression Analysis; D012189:Retrospective Studies; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D003404:Creatinine