Residual Kidney Function in ESRD: Measurements, Serum Markers and Outcomes

ESRD 中的残余肾功能：测量、血清标志物和结果

• 批准号: 8705499
• 负责人: Tariq Shafi
• 金额: $ 18.21万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-09 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8705499
• 关键词: Ancillary Study; Angiotensin-Converting Enzyme Inhibitors; Area; Award; Biometry; Blood specimen; Cardiovascular system; Caring; Clinical Investigator; Clinical Research; Clinical Trials; Collection; Complement; Congestive Heart Failure; Contrast Media; Creatinine; Cresol; Cresols; Data; Death Rate; Development; Dialysis patients; Dialysis procedure; Disease Outcome; Dose; End stage renal failure; Enrollment; Environment; Epidemiologic Studies; Epidemiology; Foundations; Funding; Glomerular Filtration Rate; Goals; Guidelines; Health; Heart failure; Hemodialysis; Hospitalization; Hour; Hypertension; Indican; Inorganic Sulfates; Institution; Iohexol; K-Series Research Career Programs; Kidney; Kidney Diseases; Kidney Failure; Knowledge; Kynurenic Acid; Left Ventricular Ejection Fraction; Left Ventricular Hypertrophy; Left Ventricular Mass; Maintenance; Masks; Measurement; Measures; Medical; Medicine; Mentors; Methods; Molecular Weight; Morbidity - disease rate; Nephrology; Outcome; Outcomes Research; Output; Participant; Patients; Peritoneal Dialysis; Persons; Pilot Projects; Placebos; Plasma; Play; Prevention Research; Proteins; Protocols documentation; Randomized; Randomized Clinical Trials; Recommendation; Recruitment Activity; Renal function; Research; Research Infrastructure; Research Personnel; Research Project Grants; Residual state; Risk; Risk Factors; Role; Series; Serum; Serum Markers; Solid; Structure; Supervision; Testing; Time; Toxin; United States National Institutes of Health; Universities; Unspecified or Sulfate Ion Sulfates; Urea; Urine; Work; career; career development; design; didactic education; experience; improved; indexing; instructor; mortality; pilot trial; placebo controlled study; post gamma-globulins; prevent; programs; prostaglandin R2 D-isomerase; standard measure; urinary

DESCRIPTION (provided by applicant): Over a 100,000 persons in the US started dialysis and more than 350,000 people were on maintenance dialysis in 2006; a number expected to grow to over half a million by the year 2020. The high first-year mortality for incident dialysis patients has not decreased in the last 11 years and 60% of the dialysis patients die within five years of starting dialysis. Therapies to improve dialysis care are sorely needed but most recent clinical trials to reduce dialysis mortality have been negative. Kidney function after starting dialysis, referred to as residual kidney function (RKF), is a strong predictor of survival in dialysis patients. RKF, even at the low levels present in dialysis patients is important for clearing uremic toxins and preventing volume overload and its sequelae such as hypertension and heart failure. Preserving RKF, as an integral part of an overall dialysis care plan, offers the hope of improving dialysis care and improving the dismal dialysis survival. RKF, however, is difficult to assess. There are no methods for assessing RKF similar to the estimation of GFR by serum creatinine in non-dialysis patients. Timed urine collection, performed over 24-48 hours is the only method available at this time to assess RKF in dialysis patients. The overall goals of this proposal are: (1) to develop simple methods for direct measurement of GFR in dialysis patients using a very small dose of iohexol, a radiologic contrast agent referred to as the new standard for measuring GFR, (2) test if two endogenous low molecular weight proteins (beta-trace protein [BTP] and cystatin C), that are excellent serum markers of GFR but not removed by dialysis, can be used to estimate GFR in dialysis patients similar to the estimation of GFR from serum creatinine in non-dialysis patients, (3) determine the risk of mortality and morbidity associated with low RKF, and (4) design and conduct a pilot randomized clinical trial to determine if RKF can be preserved by treatment with angiotensin converting enzyme inhibitors. The candidate for this mentored Career Development Award is an Instructor of Medicine in the Division of Nephrology at Johns Hopkins University and his career goal is to become an independent clinician-investigator in the area of end-stage renal disease (ESRD). This award will allow him to undergo a rigorous program of didactic education in epidemiology and biostatistics complemented with a practical experience in conducting clinical research. These structured career development activities, occurring under the close guidance and supervision of leaders in the field of kidney disease epidemiology, the supportive environment of Johns Hopkins University as well as the Welch Center for Prevention, Epidemiology, and Clinical Research will allow him to answer important scientific questions and develop into an independent clinical investigator.

描述（由申请人提供）： 2006年，美国有超过100，000人开始透析，超过350，000人接受维持性透析;预计到2020年，这一数字将增长到超过50万。在过去11年中，透析患者的第一年高死亡率没有下降，60%的透析患者在开始透析后5年内死亡。迫切需要改善透析护理的疗法，但最近降低透析死亡率的临床试验结果是负面的。开始透析后的肾功能，被称为残余肾功能（RKF），是透析患者生存率的强有力预测因素。即使在透析患者中存在低水平的RKF，对于清除尿毒症毒素和预防容量超负荷及其后遗症（如高血压和心力衰竭）也很重要。作为整体透析护理计划的组成部分，保留RKF为改善透析护理和改善惨淡的透析生存率提供了希望。然而，RKF很难评估。在非透析患者中，没有类似于通过血清肌酐估计GFR的评估RKF的方法。在24-48小时内进行的定时尿液采集是目前评估透析患者RKF的唯一可用方法。该提案的总体目标是：（1）开发使用非常小剂量的碘海醇直接测量透析患者GFR的简单方法，碘海醇是一种被称为测量GFR的新标准的放射造影剂，（2）检测两种内源性低分子量蛋白质是否（β-痕量蛋白[BTP]和胱抑素C），它们是GFR的优秀血清标志物，但不能通过透析去除，可用于估计透析患者的GFR，类似于从非透析患者的血清肌酐估计GFR，（3）确定与低RKF相关的死亡率和发病率的风险，（4）设计并进行一项初步随机临床试验，以确定血管紧张素转换酶抑制剂治疗是否可以保护RKF。 该指导职业发展奖的候选人是约翰霍普金斯大学肾脏病学部的医学讲师，他的职业目标是成为终末期肾病（ESRD）领域的独立临床研究者。该奖项将使他能够接受严格的流行病学和生物统计学教学教育计划，并辅之以进行临床研究的实践经验。这些结构化的职业发展活动，在肾脏疾病流行病学领域领导者的密切指导和监督下发生，约翰霍普金斯大学的支持性环境以及韦尔奇预防，流行病学和临床研究中心将使他能够回答重要的科学问题，并发展成为一名独立的临床研究者。

项目成果

Estimating residual kidney function in dialysis patients without urine collection.

• DOI: 10.1016/j.kint.2015.10.011
• 发表时间: 2016-05
• 期刊: Kidney international
• 影响因子: 19.6
• 作者: Shafi T;Michels WM;Levey AS;Inker LA;Dekker FW;Krediet RT;Hoekstra T;Schwartz GJ;Eckfeldt JH;Coresh J
• 通讯作者: Coresh J