title: Serum cystatin C for the prediction of glomerular filtration rate with regard to the dose adjustment of amikacin, gentamicin, tobramycin, and vancomycin.
abstract: Dosage regimes of aminoglycosides and vancomycin are modified according to the glomerular filtration rate (GFR). In 130 hospitalized patients who were administered amikacin, gentamicin, tobramycin, and vancomycin by intermittent intravenous infusion, we compared the predicted GFR values from the serum concentrations of creatinine (Cockcroft and Gault. Nephron. 1976;16:31-41) and cystatin C (Larsson et al. Scand J Clin Lab Invest. 2004;64:25-30) with respect to their relevance for proper dosage. In 83% and 67% of the cases, respectively, the serum levels of albumin and cholinesterase were below the corresponding lower limit of the reference range. The ratio of creatinine/cystatin C concentrations presented significant correlations with the predicted rate of creatinine production (r=0.762, P<0.001), serum albumin concentration (r=0.205, P<0.05), and catalytic serum concentrations of cholinesterase (r=0.207, P<0.05), gamma glutamyltransferase (r=-0.273, P<0.01), and alkaline phosphatase (r=-0.289, P<0.01). The GFR (mean+/-SD; median) predicted by the serum creatinine (84.0+/-35.1 mL/min/1.73 m; 82.6 mL/min/1.73 m) was significantly higher (P<0.001) than that predicted by the serum cystatin C (53.1+/-30.2 mL/min/1.73 m; 44.9 mL/min/1.73 m). The ratio between the GFR values predicted by creatinine and cystatin C had a highly significant negative correlation with the rate of creatinine production (r=-0.912, P<0.001). Furthermore, significant differences were found for the peak concentrations and clearances of amikacin and vancomycin estimated by means of the Abbottbase Pharmacokinetic Systems program, and using the GFR values predicted by the serum creatinine and cystatin C (P<0.005). In patients with hepatic dysfunction, the clearance of creatinine predicted by the Cockcroft-Gault formula leads to a significant overestimation of the GFR. Cystatin C seems to be a valid alternative as a GFR marker with regard to drug dose adjustment in these cases.
authors.affiliation: Laboratorio Central, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Hermida
authors.forename: J Carlos
authors.initials: JC
authors.lastname: Tutor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000583:Amikacin / Q000008:administration & dosage / Q000493:pharmacokinetics; D000617:Aminoglycosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003404:Creatinine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D016903:Drug Monitoring; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics; D005919:Glomerular Filtration Rate; D048550:Hepatic Insufficiency / Q000150:complications; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D014031:Tobramycin / Q000008:administration & dosage / Q000493:pharmacokinetics; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D005839:Gentamicins; D014640:Vancomycin; D000583:Amikacin; D003404:Creatinine; D014031:Tobramycin