Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, S976.1 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
The Center for Critical Care Nephrology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA CRISMA (Clinical Research Systems Modeling of Acute Illness) Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Nephrol Dial Transplant. 2014 Jul;29(7):1312-9. doi: 10.1093/ndt/gft503. Epub 2013 Dec 29.
A goal for scientists studying septic acute kidney injury (AKI) should be to formulate a conceptual model of disease that is able to coherently reconcile the molecular and inflammatory consequences of sepsis with impaired epithelial tubular function, diminished glomerular filtration rate (GFR) and ultimately kidney failure. Recent evidence has shed light on how sepsis modulates the tubular regulation of ion, glucose, urea and water transport and acid-base homeostasis in the kidney. The present review summarizes recent discoveries on changes in epithelial transport under septic and endotoxemic conditions as well as the mechanisms that link inflammation with impaired tubular membrane transport. This paper also proposes that the tubular dysfunction that is mediated by inflammation in sepsis ultimately leads to increased sodium and chloride delivery to the distal tubule and macula densa, contributing to tubuloglomerular feedback and impaired GFR. We feel that this conceptual model resolves many of the physiologic and clinical paradoxes that septic AKI presents to practicing researchers and clinicians.
研究脓毒症急性肾损伤（AKI）的科学家的目标应该是制定一个疾病概念模型，该模型能够将脓毒症的分子和炎症后果与上皮管状功能障碍、肾小球滤过率（GFR）降低以及最终的肾衰竭协调一致。最近的证据揭示了脓毒症如何调节肾脏中离子、葡萄糖、尿素和水转运以及酸碱平衡的管状调节。本综述总结了最近关于脓毒症和内毒素血症条件下上皮转运变化的发现，以及将炎症与管状膜转运障碍联系起来的机制。本文还提出，炎症介导的管状功能障碍最终导致钠和氯向远端肾小管和致密斑的输送增加，导致管球反馈和 GFR 受损。我们认为，这个概念模型解决了脓毒症 AKI 给实际研究人员和临床医生带来的许多生理和临床悖论。
