Steinke Thomas, Moritz Stefan, Beck Stefanie, Gnewuch Carsten, Kees Martin G
Department of Anaesthesiology and Surgical Intensive Care, University Hospital of Halle (Saale), Ernst-Grube-Str. 40, 06120, Halle (Saale), Germany.
Department of Anesthesiology, University Hospital Hamburg-Eppendorf, Martini-Str. 52, 20246, Hamburg, Germany.
BMC Anesthesiol. 2015 Apr 28;15:62. doi: 10.1186/s12871-015-0043-7.
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.
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.
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.
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.
在重症监护病房（ICU）患者中，肾小球滤过功能常常受损，但也可观察到超生理值（“增强的肾脏清除率”，>130 mL/min/1.73 m²）。经肾脏排泄的药物（如许多抗生素）必须相应调整剂量，这需要对临床所见的所有肾功能值范围进行定量测量。根据血肌酐进行估算为标准方法，但胱抑素C可能是一种有价值的替代方法。
这是对两项关于万古霉素和β-内酰胺类抗生素的药代动力学研究中的100例ICU患者的肾功能参数进行的二次分析。将通过Cockcroft-Gault公式（eCLCG）、CKD-EPI公式（eCLCKD-EPI）或基于胱抑素C的Hoek公式（eCLHoek）获得的估算清除率值与测量的内生肌酐清除率（CLCR）进行比较。通过改良的Bland-Altman图以及计算偏差（中位数误差）和精密度（中位数绝对误差）来评估值的一致性。计算估算值识别CLCR降低（<60 mL/min/1.73 m²）或增强（>130 mL/min/1.73 m²）患者的敏感性和特异性。
CLCR分布范围广，从严重受损到超生理值（中位数73.2，范围16.8 - 234 mL/min/1.73 m²），即使血肌酐未升高（女性≤0.8 mg/dL，男性≤1.1 mg/dL）。eCLCG的偏差和精密度分别为+13.5 mL/min/1.73 m²和±18.5 mL/min/1.73 m²，eCLCKD-EPI为+7.59和±16.8 mL/min/1.73 m²，eCLHoek为 - 4.15和±12.9 mL/min/1.73 m²，eCLHoek比其他两者更精确（p < 0.05）。eCLCG观察到的误差的中心95%落在 - 59.8至+250 mL/min/1.73 m²之间，eCLCKD-EPI为 - 83.9至+79.8 mL/min/1.73 m²，eCLHoek为 - 103至+27.9 mL/min/1.73 m²。eCLCKD-EPI和eCLHoek低估了增强的肾脏清除率。eCLCG、eCLCKD-EPI和eCLHoek识别CLCR降低患者的特异性良好（分别为0.95、0.97和0.91），但敏感性较低（0.55、0.55和0.83）。对于增强的肾脏清除率，特异性分别为0.81、0.96和0.96，但敏感性仅为0.69、0.25和0.38。
在ICU患者中，正常的血肌酐浓度可能具有很大的误导性。基于胱抑素C的eCLHoek与CLCR的一致性优于基于肌酐的eCLCG或eCLCKD-EPI。通过估算来检测和量化增强的肾脏清除率存在问题，应更多地依赖CLCR。
