Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, NY 12208, USA.
Adv Chronic Kidney Dis. 2010 Sep;17(5):e53-62. doi: 10.1053/j.ackd.2010.05.010.
One-third of adult Americans are currently classified as obese. Physiologic changes associated with obesity can potentially alter the clearance of commonly used drugs. Clearance of certain drugs by the kidneys occurs primarily through glomerular filtration and tubular secretion. Obesity has been associated with glomerular hyperfiltration, whereas obesity-related effects on tubular secretion are not well characterized. Estimation of the glomerular filtration rate (GFR) is currently performed using serum creatinine using the Modification of Diet in Renal Disease (MDRD) equation. However, drug dosing guidelines are often based on creatinine clearance (CLcr) using the Cockcroft-Gault equation as a surrogate of GFR. There is a lack of consensus on the most appropriate method for estimation of GFR or CLcr in patients with obesity. The controversy relates to the use of 2 body size descriptors that confound these equations. The Cockcroft-Gault equation relies on total body weight and so overestimates GFR in patients with obesity. The MDRD equation indexes GFR based on a normalized body surface area, that is, mL/min/1.73 m(2). Conversion of MDRD estimated GFR to non-normalized body surface area overestimates GFR in patients with obesity. The current review explores current approaches and controversies to estimation of GFR and CLcr among obese patients in clinical practice. The role of the alternate body size descriptor, lean body weight to estimate CLcr in obese patients is reviewed.
目前,三分之一的美国成年人被归类为肥胖。与肥胖相关的生理变化可能会改变常用药物的清除率。肾脏通过肾小球滤过和肾小管分泌来清除某些药物。肥胖与肾小球高滤过有关,而肥胖对肾小管分泌的影响尚未得到很好的描述。目前,使用血清肌酐和肾脏病饮食改良公式(MDRD)方程来估计肾小球滤过率(GFR)。然而,药物剂量指南通常基于肌酐清除率(CLcr),使用 Cockcroft-Gault 方程作为 GFR 的替代物。在肥胖患者中,对于估计 GFR 或 CLcr 最适当的方法,目前尚无共识。争议涉及到使用 2 个体型描述符,这些描述符混淆了这些方程。Cockcroft-Gault 方程依赖于总体重,因此高估了肥胖患者的 GFR。MDRD 方程基于标准化的体表面积来索引 GFR,即 mL/min/1.73 m(2)。将 MDRD 估计的 GFR 转换为非标准化的体表面积会高估肥胖患者的 GFR。本综述探讨了目前在临床实践中估计肥胖患者 GFR 和 CLcr 的方法和争议。还回顾了使用瘦体重替代体型描述符来估计肥胖患者 CLcr 的作用。