Tubular Secretion in Chronic Kidney Disease

慢性肾病的肾小管分泌

• 批准号: 9008641
• 负责人: BRYAN R KESTENBAUM
• 金额: $ 73.24万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9008641
• 关键词: Acidosis; Albuminuria; Anemia; Applications Grants; Binding Proteins; Biological Assay; Biological Process; Blood Circulation; Cardiovascular system; Cefazolin; Cephalexin; Charge; Chronic Kidney Failure; Chronic Kidney Insufficiency; Clinical; Clinical Research; Cohort Studies; Collection; Cresol; Detection; Development; Disease Progression; Dose; Early Diagnosis; Epidemiology; Equation; Event; Fatigue; Furosemide; Glomerular Filtration Rate; Gold; Grant; Hour; Human; Hyperparathyroidism; Indican; Individual; Inorganic Sulfates; Iohexol; Kidney; Kidney Diseases; Laboratories; Mass Spectrum Analysis; Measurement; Measures; Medicine; Metabolic; Monitor; Nature; Nephrology; Outcome; Participant; Patients; Pharmaceutical Preparations; Pharmacology; Physiological; Population; Recruitment Activity; Renal Plasma Flow; Renal clearance function; Renal function; Severities; Specificity; Time; Tubular formation; Unspecified or Sulfate Ion Sulfates; Urine; base; burden of illness; clinical care; clinical practice; cohort; drug clearance; follow-up; glomerular basement membrane; glomerular filtration; improved; interdisciplinary collaboration; mortality; novel; prospective; public health relevance; solute; urinary

 DESCRIPTION (provided by applicant): The glomerular filtration rate (GFR) is the established measurement of kidney function that is used to define the presence and severity of chronic kidney disease (CKD). The diverse physiological functions of the kidneys are unlikely to be captured by GFR alone. Proximal tubule secretion is an essential, kidney-specific mechanism for rapidly eliminating retained solutes and administered medications from the circulation. We developed and validated novel assays to measure endogenous markers that are primary cleared by proximal tubule secretion. We used these markers to demonstrate considerable individual-level variability in estimated tubule secretion function relative to GFR among CKD patients. This grant proposes two parallel aims to advance understanding of proximal tubule secretion function. First, we will estimate secretion function in the prospective Chronic Renal Insufficiency Cohort study and determine associations with CKD complications and major clinical outcomes. Second, we will recruit a primary cohort of patients across a broad range of kidney function and compare estimated tubule secretion function versus GFR for predicting renal drug clearances. Potential applications of the proposed studies include earlier detection of CKD, improved monitoring of kidney disease patients, and optimized renal medication dosing strategies.

 描述（由申请方提供）：肾小球滤过率（GFR）是肾功能的既定指标，用于确定慢性肾脏疾病（CKD）的存在和严重程度。肾脏的各种生理功能不太可能仅由GFR捕获。近端小管分泌是一种重要的肾脏特异性机制，用于快速清除循环中残留的溶质和给药药物。我们开发并验证了新的测定方法，以测量主要通过近端小管分泌清除的内源性标志物。我们使用这些标记物来证明CKD患者中相对于GFR的估计小管分泌功能的相当大的个体水平变异性。该基金提出了两个平行的目标，以促进对近端小管分泌功能的理解。首先，我们将在前瞻性慢性肾功能不全队列研究中评估分泌功能，并确定与CKD并发症和主要临床结局的相关性。其次，我们将招募一个主要队列的患者在广泛的肾功能和比较估计肾小管分泌功能与GFR预测肾脏药物清除率。拟议研究的潜在应用包括早期检测CKD，改善对肾脏疾病患者的监测，以及优化肾脏药物给药策略。