Role of Kidney Proximal Tubular Secretion in Critical Illness

项目摘要 急性肾损伤（阿基）是糖尿病患者中最常见的器官功能障碍类型之一。 重症监护室（ICU）。阿基的大多数原因涉及肾脏近端小管的损伤。但是，在这方面， 阿基的临床评价依赖于血清肌酸酐的测量作为肾小球滤过的标志。 因此，阿基的严重程度和临床意义可能与疾病的生物学不一致。 由于缺乏可靠的方法和不确定性，很少测量近端肾小管分泌清除率 关于临床解释。我们开发了一种新的靶向质谱分析，以估计管状 基于血浆和尿液中内源性分泌溶质的定量的分泌清除率，我们 表明肾小管分泌清除与慢性肾脏疾病的进展有关 和死亡率独立于估计的肾小球滤过率。 本申请的总体目标是通过增加功能性评估来推进阿基的临床评估。 与疾病的潜在机制相一致的测量。我们建议测量管状 在具有发生阿基的高风险的危重成年人的前瞻性队列中进行分泌清除。我们 将评估肾小管分泌和肾小球滤过下降的潜在共同和独特风险因素， 确定肾小管分泌清除率是否增加了测量的药物水平的预测，并测试 较低的分泌清除率是否与ICU谵妄、昏迷以及 阿基 1

Project Abstract Acute kidney injury (AKI) is one of the most common types of organ dysfunction among persons in the intensive care unit (ICU). Most causes of AKI involve injury to the proximal tubules of the kidneys. However, clinical evaluation of AKI relies on measurements of serum creatinine as a marker of glomerular filtration. Consequently, the severity and clinical implications of AKI may be misaligned with the biology of the disease. Proximal tubular secretory clearance is rarely measured due to a lack of reliable methods and uncertainty regarding clinical interpretation. We developed a novel targeted mass spectrometric assay to estimate tubular secretory clearance based on quantification of endogenous secretory solutes in plasma and urine, and we demonstrated that tubular secretory clearance is associated with the progression of chronic kidney disease and mortality independent of the estimated glomerular filtration rate. The general goal of this application is to advance clinical assessment of AKI by adding functional measurements that align with the underlying mechanisms of disease. We propose to measure tubular secretory clearances in a prospective cohort of critically ill adults who are at high risk for developing AKI. We will assess potential shared and unique risk factors for decline in tubular secretion and glomerular filtration, determine whether tubular secretory clearance adds to the prediction of measured drug levels, and test whether lower secretory clearance is associated with ICU delirium, coma and the severity and prognosis of AKI. 1