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 (eCL(CG)), the CKD-EPI formula (eCL(CKD-EPI)) or the cystatin C based Hoek formula (eCL(Hoek)) 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 eCL(CG), +7.59 and +/- 16.8 mL/min/1.73 m(2) for eCL(CKD-EPI), and -4.15 and +/- 12.9 mL/min/1.73m(2) for eCL(Hoek), respectively, with eCL(Hoek) 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 eCL(CG), -83.9 and +79.8 mL/min/1.73 m(2) for eCL(CKD-EPI), and -103 and +27.9 mL/min/1.73 m(2) for eCL(Hoek). Augmented renal clearance was underestimated by eCL(CKD-EPI) and eCL(Hoek). Patients with reduced CLCR were identified with good specificity by eCL(CG), eCL(CKD-EPI) and eCL(Hoek) (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 eCL(Hoek) with CLCR is better than that of the creatinine based eCL(CG) or eCL(CKD-EPI). Detection and quantification of augmented renal clearance by estimates is problematic, and should rather rely on CLCR.