Okparavero Aghogho A, Tighiouart Hocine, Krishnasami Zipporah, Wyatt Christina M, Graham Hiba, Hellinger James, Inker Lesley A
Department of Medicine, Tufts Medical Center, Boston, MA, USA.
Antivir Ther. 2013;18(6):793-802. doi: 10.3851/IMP2676. Epub 2013 Aug 20.
Current HIV treatment guidelines recommend using the Cockcroft-Gault equation for drug dosing adjustments. The use of newer glomerular filtration rate (GFR) estimating equations for drug dosing and the appropriateness of physician antiretroviral dosing based on estimated kidney function have not been studied in an HIV-positive population.
We evaluated concordance between measured and estimated GFR for the assignment of kidney function categories designated by the US Food and Drug Administration (FDA) Guidance for industry for pharmacokinetic studies, and appropriateness of physician antiretroviral drug dosing for level of kidney function in 200 HIV-positive patients on stable antiretroviral therapy. Estimated kidney function was determined using the Chronic Kidney Disease-Epidemiology collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study and Cockcroft-Gault equations.
For assignment of FDA-designated kidney function categories, concordance rates between measured and estimated GFR using the CKD-EPI, MDRD Study and Cockcroft-Gault equations were 79%, 71% and 77%, respectively. This pattern was consistent across most subgroups. When actual prescribed dosages were compared with recommended dosages based on the level of estimated kidney function, 3-19% of study participants were prescribed higher than recommended dosages. The largest discordance between prescribed and recommended dosages was observed for the Cockcroft-Gault equation.
The CKD-EPI equation has the highest concordance with measured GFR for the assignment of FDA-designated kidney function categories. Its use may lead to lower dosing-related errors in HIV-infected US adults on stable antiretroviral therapy. More education is required with respect to dose adjustment for level of kidney function.
当前的艾滋病病毒治疗指南建议使用Cockcroft-Gault方程进行药物剂量调整。在艾滋病病毒阳性人群中，尚未研究使用更新的肾小球滤过率（GFR）估算方程进行药物剂量调整以及基于估算肾功能的医生抗逆转录病毒药物剂量的适宜性。
我们评估了200例接受稳定抗逆转录病毒治疗的艾滋病病毒阳性患者中，实测GFR与估算GFR之间的一致性，以确定美国食品药品监督管理局（FDA）药物动力学研究行业指南指定的肾功能类别，以及医生抗逆转录病毒药物剂量对于肾功能水平的适宜性。使用慢性肾脏病流行病学合作（CKD-EPI）方程、肾脏病饮食改良（MDRD）研究方程和Cockcroft-Gault方程来确定估算肾功能。
对于FDA指定的肾功能类别，使用CKD-EPI方程、MDRD研究方程和Cockcroft-Gault方程时，实测GFR与估算GFR之间的一致性率分别为79%、71%和77%。这种模式在大多数亚组中是一致的。当将实际规定剂量与基于估算肾功能水平的推荐剂量进行比较时，3%-19%的研究参与者被给予了高于推荐剂量的药物。在规定剂量与推荐剂量之间观察到的最大差异是Cockcroft-Gault方程。
对于FDA指定的肾功能类别，CKD-EPI方程与实测GFR的一致性最高。在接受稳定抗逆转录病毒治疗的美国艾滋病病毒感染成年人中，使用该方程可能会减少与剂量相关的错误。在肾功能水平的剂量调整方面需要更多的教育。
