Evaluation of the clinical application of cystatin C, a new marker of the glomerular filtration rate, for the initial dose-setting of arbekacin.
OBJECTIVE
Recent studies have shown that serum cystatin C is a better marker for measuring the glomerular filtration rate (GFR) than the conventional method, using serum creatinine concentration. The purpose of this study is to evaluate the clinical application of serum cystatin C as a marker of GFR to determine the initial dosage of arbekacin, an antibiotic primarily excreted via the kidneys. In this study, the predictability of serum arbekacin peak and trough concentrations were assessed using estimated population mean GFR values calculated from either serum creatinine (Cockcroft-Gault equation) or cystatin C (Sjöström equation) concentrations.


METHODS
Ninety-five patients treated with arbekacin for methicillin-resistant Staphylococcus aureus infection were divided into three groups according to their GFR values estimated by the serum cystatin C concentration as follows: normal to mild (GFR > 70 mL/min, n = 40), moderate (30 </= GFR </= 70 mL/min, n = 41) and severe (GFR < 30 mL/min, n = 14) renal impairment.


RESULTS
The mean GFR (+/-SD) of 95 patients predicted by serum cystatin C concentration (64.6 +/- 30.6 mL/min) was significantly lower (P < 0.001) than predicted by serum creatinine concentration (77.4 +/- 43.9 mL/min). Prediction (difference of mean prediction error, DeltaME) of the serum arbekacin concentration using the estimated GFR based on the serum cystatin C concentration was significantly less biased at the peak and trough concentrations than those determined using serum creatinine concentration. The accuracy of prediction (difference of the mean absolute error, DeltaMAE) using serum cystatin C concentration was significantly better than with serum creatinine for both serum peak and trough concentrations in patients with moderately decreased GFR. However, there were no significant differences in the DeltaMAE of normal to mild and severe renally impaired patients.


CONCLUSIONS
These results suggest that serum cystatin C is a useful marker of GFR for determining the initial dosage of arbekacin, especially in patients with moderate impairment of renal function.
Otsuka
T
T
Department of Hospital Pharmacy, Matsuyama Shimin Hospital, Matsuyama, Japan.
Tanaka
A
A
Suemaru
K
K
Inoue
T
T
Nishimiya
T
T
Murase
M
M
Araki
H
H
D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D003982:Dibekacin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016903:Drug Monitoring; D005260:Female; D005919:Glomerular Filtration Rate; D006785:Hospitals, University; D006801:Humans; D008297:Male; D016106:Methicillin Resistance; D051437:Renal Insufficiency / Q000097:blood / Q000175:diagnosis / Q000378:metabolism; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism
D000900:Anti-Bacterial Agents; D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D003982:Dibekacin; D003404:Creatinine; C031986:arbekacin