Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
Ann Pharmacother. 2010 Mar;44(3):439-46. doi: 10.1345/aph.1M602. Epub 2010 Feb 17.
Since the derivation of the Modification of Diet in Renal Disease (MDRD) equation for estimating glomerular filtration rate (GFR), investigators determined that it cannot be used for drug dosing. In 2009, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) derived an equation that was more accurate than the MDRD estimation of GFR. Therefore, questions exist about which method should be preferred in making dosage adjustments for renally eliminated antimicrobials.
To determine whether a difference exists when making antimicrobial dosage adjustments in patients with CKD based on estimation of GFR using the CKD-EPI and Cockcroft-Gault equations.
A database of 409 patients with CKD admitted to a tertiary care facility was used. GFR was calculated using both the CKD-EPI equation(s) and the Cockcroft-Gault equation and compared using correlation and Bland-Altman methodology. Dosage discordance rates of antimicrobials were determined.
Average GFRs for all patients using the Cockcroft-Gault and CKD-EPI equations were 34.8 +/- 12 mL/min and 39.9 +/- 13 mL/min, respectively (5.09 [95% CI 4.60 to 5.59]; p < 0.001). The correlation coefficient between the 2 estimations was high (r = 0.91). The Bland-Altman plot yielded limits of agreement of 15.3 and -5.1; thus, the CKD-EPI estimation may range from 5.1 mL/min below to 15.3 mL/min above the Cockcroft-Gault estimation for 95% of the cases. A discordance rate of 15-25% existed among the recommended dosing adjustments of the selected antimicrobials when comparing the Cockcroft-Gault and CKD-EPI estimations.
Though this study did not determine which equation should be selected to dose adjust antimicrobials, it demonstrated statistically significant differences between the Cockcroft-Gault and CKD-EPI equations. The clinical significance of these differences is uncertain in the absence of data assessing clinical outcomes that result from the use of the discordant doses. Clinical judgment should be employed when making renal dosage adjustments of antimicrobials.
自用于估计肾小球滤过率(GFR)的肾脏病饮食改良公式(MDRD)推导以来,研究人员确定它不能用于药物剂量调整。2009 年,慢性肾脏病流行病学合作(CKD-EPI)推导出的公式比 MDRD 对 GFR 的估计更准确。因此,在对肾清除的抗菌药物进行剂量调整时,存在关于应首选哪种方法的问题。
确定在使用 CKD-EPI 和 Cockcroft-Gault 方程估计 GFR 的情况下,对 CKD 患者进行抗菌药物剂量调整时是否存在差异。
使用三级保健机构收治的 409 例 CKD 患者的数据库。使用 CKD-EPI 方程和 Cockcroft-Gault 方程计算 GFR,并使用相关和 Bland-Altman 方法进行比较。确定抗菌药物剂量不匹配的发生率。
所有患者使用 Cockcroft-Gault 和 CKD-EPI 方程的平均 GFR 分别为 34.8+/-12mL/min 和 39.9+/-13mL/min(5.09[95%CI 4.60 至 5.59];p<0.001)。两种估计之间的相关系数很高(r=0.91)。Bland-Altman 图产生的一致性界限为 15.3 和-5.1;因此,对于 95%的病例,CKD-EPI 估计值可能在 Cockcroft-Gault 估计值的 5.1 mL/min 以下和 15.3 mL/min 以上范围内。当比较 Cockcroft-Gault 和 CKD-EPI 估计值时,所选抗菌药物的推荐剂量调整之间存在 15%-25%的不匹配率。
尽管本研究并未确定应选择哪种方程来调整抗菌药物剂量,但它表明 Cockcroft-Gault 和 CKD-EPI 方程之间存在统计学显著差异。在缺乏评估使用不匹配剂量导致的临床结果数据的情况下,这些差异的临床意义尚不确定。在对肾清除的抗菌药物进行剂量调整时,应运用临床判断。