Zhou Ling-Yun, Yin Wen-Jun, Zhao Jun, Zhang Bi-Kui, Hu Can, Liu Kun, Wang Jiang-Lin, Zhou Ge, Chen Lin-Hua, Zuo Shan-Ru, Xie Yue-Liang, Zuo Xiao-Cong
Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Clinical Pharmacy, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China.
Front Pharmacol. 2021 Feb 19;12:615953. doi: 10.3389/fphar.2021.615953. eCollection 2021.
Over/under-estimating renal function may increase inappropriate dosing strategy associated adverse outcomes; however, previously reported equations to estimate renal function have limited accuracy in chronic kidney disease (CKD) patients. Consequently, we intended to develop a novel equation to precisely estimate renal function and subsequently guide clinical treatment for CKD patients. A novel approach, Xiangya-s equation, to estimate renal function for CKD patients was derived by linear regression analysis and validated in 1885 patients with measured glomerular filtration rate (mGFR) < 60 ml/min/1.73 m by renal dynamic imaging at three representative hospitals in China, with the performance evaluated by accuracy, bias and precision. In the meanwhile, 2,165 atrial fibrillation (AF) patients who initiated direct oral anticoagulants (DOACs) between December 2015 and December 2018 were identified and renal function was assessed by estimated creatinine clearance (eCrCl). Events per 100 patient-years was calculated. Cox proportional hazards regression was applied to compare the incidence of outcomes of each group. Xiangya-s equation demonstrated higher accuracy, lower bias and improved precision when compared with 12 creatinine-based and 2 CysC-based reported equations to estimate GFR in multi-ethnic Chinese CKD patients. When we applied Xiangya-s equation to patients with AF and CKD prescribed DOACs, wide variability was discovered in eCrCl calculated by the Cockcroft-Gault (CG), Modification of Diet in Renal Disease Study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Xiangya equation which we had developed for generally patients and Xiangya-s equations, which persisted after grouping by different renal function stages. Equation choice affected drug-dosing adjustments, with the formulas agreeing for only 1.19%, 5.52%, 33.22%, 26.32%, and 36.61% of potentially impacted patients for eCrCl cutoffs of <15, <30, 15-49, 30-49, ≥50 ml/min, respectively. Relative to CG equation, accordance in DOACs dosage was 81.08%, 88.54%, 62.25%, and 47.68% for MDRD, CKD-EPI, Xiangya and Xiangya-s equations for patients with CrCl < 50 ml/min (eCrCl cutoffs of <30, 30-49, ≥50 ml/min), respectively. Reclassification of renal function stages by Xiangya-s equation was significantly associated with stroke or systemic embolism, non-major clinically relevant bleeding and any bleeding events. Xiangya-s equation provides more accurate GFR estimates in Chinese CKD patients who need consecutive monitoring of renal function, which may assist clinicians in choosing appropriate drug dosages.
高估或低估肾功能可能会增加与不适当给药策略相关的不良后果；然而，先前报道的估算肾功能的公式在慢性肾脏病（CKD）患者中准确性有限。因此，我们旨在开发一种新的公式来精确估算肾功能，进而指导CKD患者的临床治疗。通过线性回归分析得出了一种用于估算CKD患者肾功能的新方法——湘雅s公式，并在中国三家代表性医院对1885例肾小球滤过率（mGFR）<60 ml/min/1.73 m²且通过肾动态显像测量的患者进行了验证，通过准确性、偏差和精密度对其性能进行评估。同时，确定了2165例在2015年12月至2018年12月期间开始使用直接口服抗凝剂（DOACs）的心房颤动（AF）患者，并通过估算的肌酐清除率（eCrCl）评估肾功能。计算每100患者年的事件数。应用Cox比例风险回归比较各组结局的发生率。与12个基于肌酐的和2个基于胱抑素C的已报道公式相比，湘雅s公式在多民族中国CKD患者中估算肾小球滤过率时显示出更高的准确性、更低的偏差和更高的精密度。当我们将湘雅s公式应用于使用DOACs的AF和CKD患者时，发现通过Cockcroft-Gault（CG）公式、肾脏病膳食改良研究（MDRD）公式、慢性肾脏病流行病学协作组（CKD-EPI）公式、我们为一般患者开发的湘雅公式以及湘雅s公式计算的eCrCl存在很大差异，按不同肾功能阶段分组后这种差异仍然存在。公式选择会影响药物剂量调整，对于eCrCl临界值<15、<30、15 - 49、30 - 49、≥50 ml/min，各公式对潜在受影响患者的一致性分别仅为1.19%、5.52%、33.22%、26.32%和36.61%。对于肌酐清除率<50 ml/min（eCrCl临界值<30、30 - 49、≥50 ml/min）的患者，相对于CG公式，MDRD公式、CKD-EPI公式、湘雅公式和湘雅s公式在DOACs剂量方面的一致性分别为81.08%、88.54%、62.25%和47.68%。通过湘雅s公式重新分类肾功能阶段与中风或全身性栓塞、非重大临床相关出血及任何出血事件显著相关。湘雅s公式在需要连续监测肾功能的中国CKD患者中提供了更准确的肾小球滤过率估算值，这可能有助于临床医生选择合适的药物剂量。
