Estimation of creatinine clearance using plasma creatinine or cystatin C: a secondary analysis of two pharmacokinetic studies in surgical ICU patients.
BACKGROUND
In ICU patients, glomerular filtration is often impaired, but also supraphysiological values are observed ("augmented renal clearance", >130 mL/min/1.73 m(2)). Renally eliminated drugs (e.g. many antibiotics) must be adjusted accordingly, which requires a quantitative measure of renal function throughout all the range of clinically encountered values. Estimation from plasma creatinine is standard, but cystatin C may be a valuable alternative.


METHODS
This was a secondary analysis of renal function parameters in 100 ICU patients from two pharmacokinetic studies on vancomycin and betalactam antibiotics. Estimated clearance values obtained by the Cockcroft-Gault formula (eCLCG), the CKD-EPI formula (eCLCKD-EPI) or the cystatin C based Hoek formula (eCLHoek) were compared with the measured endogenous creatinine clearance (CLCR). Agreement of values was assessed by modified Bland-Altman plots and by calculating bias (median error) and precision (median absolute error). Sensitivity and specificity of estimates to identify patients with reduced (<60 mL/min/1.73 m(2)) or augmented (>130 mL/min/1.73 m(2)) CLCR were calculated.


RESULTS
The CLCR was well distributed from highly compromised to supraphysiological values (median 73.2, range 16.8-234 mL/min/1.73 m(2)), even when plasma creatinine was not elevated (≤0.8 mg/dL for women, ≤1.1 mg/dL for men). Bias and precision were +13.5 mL/min/1.73 m(2) and ±18.5 mL/min/1.73 m(2) for eCLCG, +7.59 and ±16.8 mL/min/1.73 m(2) for eCLCKD-EPI, and -4.15 and ±12.9 mL/min/1.73 m(2) for eCLHoek, respectively, with eCLHoek being more precise than the other two (p < 0.05). The central 95% of observed errors fell between -59.8 and +250 mL/min/1.73 m(2) for eCLCG, -83.9 and +79.8 mL/min/1.73 m(2) for eCLCKD-EPI, and -103 and +27.9 mL/min/1.73 m(2) for eCLHoek. Augmented renal clearance was underestimated by eCLCKD-EPI and eCLHoek. Patients with reduced CLCR were identified with good specificity by eCLCG, eCLCKD-EPI and eCLHoek (0.95, 0.97 and 0.91, respectively), but with less sensitivity (0.55, 0.55 and 0.83). For augmented renal clearance, specificity was 0.81, 0.96 and 0.96, but sensitivity only 0.69, 0.25 and 0.38.


CONCLUSIONS
Normal plasma creatinine concentrations can be highly misleading in ICU patients. Agreement of the cystatin C based eCLHoek with CLCR is better than that of the creatinine based eCLCG or eCLCKD-EPI. Detection and quantification of augmented renal clearance by estimates is problematic, and should rather rely on CLCR.
Department of Anaesthesiology and Surgical Intensive Care, University Hospital of Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany. thomas.steinke@uk-halle.de.
Thomas
T
Steinke
Department of Anaesthesiology and Surgical Intensive Care, University Hospital of Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany. stefan.moritz@uk-halle.de.
Stefan
S
Moritz
Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Martini-Str. 52, 20246, Hamburg, Germany. st.beck@uke.de.
Stefanie
S
Beck
Institute for Clinical Chemistry and Laboratory Medicine, Regensburg University Medical Center, Franz-Josef-Strauß-Allee 11, 93053, Regensburg, Germany. carsten.gnewuch@klinik.uni-regensburg.de.
Carsten
C
Gnewuch
Department of Anesthesiology and Intensive Care, Charité Universitätsmedizin Berlin - Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. martin.kees@charite.de.|Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169, Berlin, Germany. martin.kees@charite.de.
Martin G
MG
Kees
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood* / Q000652:urine; D003422:Critical Care; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007677:Kidney Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D014640:Vancomycin / Q000493:pharmacokinetics; D055815:Young Adult; D047090:beta-Lactams / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D055316:Cystatin C; D047090:beta-Lactams; D014640:Vancomycin; D003404:Creatinine