Udy Andrew A, Jarrett Paul, Stuart Janine, Lassig-Smith Melissa, Starr Therese, Dunlop Rachel, Wallis Steven C, Roberts Jason A, Lipman Jeffrey
Department of Intensive Care and Hyperbaric Medicine, The Alfred, 55 Commercial Road, Prahran, Melbourne, Victoria, 3181, Australia.
Burns, Trauma, and Critical Care Research Centre, The University of Queensland, Herston, Brisbane, Queensland, 4029, Australia.
Crit Care. 2014 Nov 29;18(6):657. doi: 10.1186/s13054-014-0657-z.
The aim of this study was to explore changes in glomerular filtration (GFR) and renal tubular function in critically ill patients at risk of augmented renal clearance (ARC), using exogenous marker compounds.
This prospective, observational pharmacokinetic (PK) study was performed in a university-affiliated, tertiary-level, adult intensive care unit (ICU). Patients aged less than or equal to 60 years, manifesting a systemic inflammatory response, with an expected ICU length of stay more than 24 hours, no evidence of acute renal impairment (plasma creatinine concentration < 120 μmol/L) and no history of chronic kidney disease or renal replacement therapy were eligible for inclusion. The following study markers were administered concurrently: sinistrin 2,500 mg (Inutest; Laevosan, Linz, Austria), p-aminohippuric acid (PAH) 440 mg (4% p-aminohippuric acid sodium salt; CFM Oskar Tropitzsch, Marktredwitz, Germany), rac-pindolol 5 or 15 mg (Barbloc; Alphapharm, Millers Point, NSW, Australia) and fluconazole 100 mg (Diflucan; Pfizer Australia Pty Ltd, West Ryde, NSW, Australia). Plasma concentrations were then measured at 5, 10, 15, 30, 60 and 120 minutes and 4, 6, 12 and 24 hours post-administration. Non-compartmental PK analysis was used to quantify GFR, tubular secretion and tubular reabsorption.
Twenty patients were included in the study. Marker administration was well tolerated, with no adverse events reported. Sinistrin clearance as a marker of GFR was significantly elevated (mean, 180 (95% confidence interval (CI), 141 to 219) ml/min) and correlated well with creatinine clearance (r = 0.70, P < 0.01). Net tubular secretion of PAH, a marker of tubular anion secretion, was also elevated (mean, 428 (95% CI, 306 to 550) ml/min), as was net tubular reabsorption of fluconazole (mean, 135 (95% CI, 100 to 169) ml/min). Net tubular secretion of (S)- and (R)-pinodolol, a marker of tubular cation secretion, was impaired.
In critically ill patients at risk of ARC, significant alterations in glomerular filtration, renal tubular secretion and tubular reabsorption are apparent. This has implications for accurate dosing of renally eliminated drugs.
本研究旨在使用外源性标记化合物，探讨有肾清除率增加（ARC）风险的危重症患者的肾小球滤过（GFR）和肾小管功能变化。
这项前瞻性观察性药代动力学（PK）研究在一所大学附属的三级成人重症监护病房（ICU）进行。年龄小于或等于60岁、表现出全身炎症反应、预计在ICU停留时间超过24小时、无急性肾损伤证据（血浆肌酐浓度<120μmol/L）且无慢性肾脏病或肾脏替代治疗史的患者符合纳入标准。同时给予以下研究标记物：2500mg的新斯的明（Inutest；奥地利林茨的Laevosan公司）、440mg的对氨基马尿酸（PAH）（4%对氨基马尿酸钠盐；德国马克特雷德维茨的CFM Oskar Tropitzsch公司）、5mg或15mg的消旋心得安（Barbloc；澳大利亚新南威尔士州米勒斯角的Alphapharm公司）和100mg的氟康唑（Diflucan；澳大利亚新南威尔士州西赖德的辉瑞澳大利亚私人有限公司）。然后在给药后5、10、15、30、60和120分钟以及4、6、12和24小时测量血浆浓度。采用非房室PK分析来量化GFR、肾小管分泌和肾小管重吸收。
20名患者纳入本研究。标记物给药耐受性良好，未报告不良事件。作为GFR标志物的新斯的明清除率显著升高（平均值为180（95%置信区间（CI），141至219）ml/min），且与肌酐清除率相关性良好（r = 0.70，P < 0.01）。作为肾小管阴离子分泌标志物的PAH的净肾小管分泌也升高（平均值为428（95%CI，306至550）ml/min），氟康唑的净肾小管重吸收也升高（平均值为135（95%CI，100至169）ml/min）。作为肾小管阳离子分泌标志物的（S）-和（R）-心得安的净肾小管分泌受损。
在有ARC风险的危重症患者中，肾小球滤过、肾小管分泌和肾小管重吸收有明显改变。这对经肾脏消除药物的准确给药有影响。
Zotero 插件
