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

• 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
• 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

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)是老年人最常见的器官功能障碍类型之一。 重症监护病房(ICU)。大多数AKI的原因涉及肾脏近端小管的损伤。然而， AKI的临床评估依赖于作为肾小球滤过标志物的血清肌酐的测量。 因此，AKI的严重性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，近端肾小管的分泌清除量很少被测量。 关于临床解释。我们开发了一种新的靶向质谱学分析方法来评估肾小管 基于血浆和尿液中内源性分泌溶质的定量的分泌清除，我们 证明肾小管分泌物清除与慢性肾脏疾病的进展有关 死亡率与估计的肾小球滤过率无关。 此应用程序的总体目标是通过添加功能 与疾病的潜在机制相一致的测量。我们建议测量管状 AKI高危人群中的分泌物清除情况。我们 将评估潜在的共同和独特的肾小管分泌物和肾小球滤过功能下降的危险因素， 确定肾小管分泌清除量是否有助于预测测得的药物浓度，并进行检验 分泌物清除量降低是否与ICU的神志不清、昏迷以及脑血管疾病的严重程度和预后有关 阿琪。 1