Role of Kidney Proximal Tubular Secretion in Critical Illness

肾近端肾小管分泌在危重疾病中的作用

基本信息

批准号：
10398127
负责人：
BRYAN R KESTENBAUM
金额：
$ 68.67万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10398127
关键词：
Acute Acute Renal Failure with Renal Papillary Necrosis Adult Affect Antibiotics Apical Binding Proteins Biological Assay Biological Markers Biology Blood Pressure Cardiac Cells Cessation of life Chronic Kidney Failure Clinical Clinical assessments Cognitive Coma Complication Creatinine Critical Care Critical Illness Delirium Dialysis procedure Disease Disease Progression Diuretics Dose Endothelium Event Excision Filtration Functional disorder Glomerular Filtration Rate Goals Hospitalization Hospitals Hypoxemia Impairment Incidence Injury Injury to Kidney Intensive Care Units Ischemia Kidney Laboratories Link Measurement Measures Medicine Methods Modality Molecular Weight Nature Nephrology Observational Study Organ Outcome Oxygen Pathway interactions Patients Persons Pharmaceutical Preparations Pharmacology Plasma Predisposition Prognosis Prospective cohort Proximal Kidney Tubules Renal function Reperfusion Therapy Risk Risk Factors Role Serum Severities Staging Testing Toxin Tubular formation Uncertainty Urea Urine Vasoconstrictor Agents Work base dosage endothelial dysfunction glomerular filtration high risk kidney dysfunction mitochondrial dysfunction mortality nephrotoxicity novel research clinical testing risk sharing sedative solute

项目摘要

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

项目摘要急性肾损伤（AKI）是人类最常见的器官功能障碍类型之一重症监护病房（ICU）。 AKI 的大多数原因涉及肾脏近端小管损伤。然而， AKI 的临床评估依赖于血清肌酐的测量作为肾小球滤过的标志物。因此，AKI 的严重程度和临床意义可能与该疾病的生物学特性不一致。由于缺乏可靠的方法和不确定性，近端肾小管分泌清除率很少测量关于临床解释。我们开发了一种新颖的靶向质谱测定法来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，我们证明肾小管分泌清除与慢性肾脏疾病的进展相关和死亡率与估计的肾小球滤过率无关。该应用程序的总体目标是通过添加功能来推进 AKI 的临床评估与疾病的潜在机制相一致的测量。我们建议测量管状一组患有 AKI 的高风险危重成人的前瞻性队列中的分泌物清除率。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是否有助于预测测量的药物水平，并测试较低的分泌清除率是否与 ICU 谵妄、昏迷及其严重程度和预后相关急性肾损伤。 1