Division of Nephrology, Department of Medicine and.
Kidney Research Institute, University of Washington, Seattle, Washington.
Clin J Am Soc Nephrol. 2018 Aug 7;13(8):1291-1296. doi: 10.2215/CJN.12001017. Epub 2018 Feb 28.
The secretion of small molecules by the proximal tubules of the kidneys represents a vital homeostatic function for rapidly clearing endogenous solutes and medications from the circulation. After filtration at the glomerulus, renal blood flow is directed through a network of peritubular capillaries, where transporters of the proximal tubules actively secrete putative uremic toxins and hundreds of commonly prescribed drugs into the urine, including protein-bound substances that cannot readily cross the glomerular basement membrane. Despite its central physiologic importance, tubular secretory clearance is rarely measured or even estimated in clinical or research settings. Major barriers to estimating tubular solute clearance include uncertainty regarding optimal endogenous secretory markers and a lack of standardized laboratory assays. The creation of new methods to measure tubular secretion could catalyze advances in kidney disease research and clinical care. Differences in secretory clearance relative to the GFR could help distinguish among the causes of CKD, particularly for disorders that primarily affect the tubulointerstitium. As the primary mechanism by which the kidneys excrete medications, tubular secretory clearance offers promise for improving kidney medication dosing, which is currently exclusively on the basis of filtration. The differing metabolic profiles of retained solutes eliminated by secretion versus glomerular filtration suggest that secretory clearance could uniquely inform uremic toxicity, refine existing measures of residual kidney function, and improve prediction of cardiovascular and kidney disease outcomes. Interdisciplinary research across clinical, translational, and laboratory medicine is needed to bring this often neglected kidney function into the limelight.
肾脏近端小管分泌的小分子对于迅速清除循环中的内源性溶质和药物是至关重要的。在肾小球滤过之后，肾血流通过肾小管周围毛细血管网络被导向，其中近端小管的转运蛋白将潜在的尿毒症毒素和数百种常用药物主动分泌到尿液中，包括无法轻易穿过肾小球基底膜的蛋白结合物质。尽管其在生理学上具有核心重要性，但在临床或研究环境中，肾小管分泌清除率很少被测量甚至估计。估计肾小管溶质清除率的主要障碍包括对最佳内源性分泌标志物的不确定性以及缺乏标准化的实验室检测方法。开发新的方法来测量肾小管分泌可以促进肾脏病研究和临床护理的进展。与 GFR 相比，分泌清除率的差异可以帮助区分 CKD 的病因，特别是对于主要影响肾小管间质的疾病。作为肾脏排泄药物的主要机制，肾小管分泌清除率为改善肾脏药物剂量提供了希望，目前肾脏药物剂量完全基于滤过。通过分泌而非肾小球滤过排泄的保留溶质的代谢特征不同表明，分泌清除率可以独特地提示尿毒症毒性，改进现有的残余肾功能评估方法，并改善心血管和肾脏疾病结局的预测。需要跨临床、转化和实验室医学的跨学科研究，将这一经常被忽视的肾脏功能置于聚光灯下。
