Chronic Renal Disease-Individual Patient Meta Analysis

描述（由申请人提供）：慢性肾脏疾病是一个全球性的公共卫生问题，发病率和患病率不断上升，预后差，成本高。本研究应用的总体目的是使用个体患者数据荟萃分析，为改善慢性肾脏疾病患者的临床护理提供必要的证据。目前的资助期主要集中在收集血管紧张素转换酶抑制剂的随机临床试验数据，以减缓非糖尿病肾病的进展。这项研究的开展产生了高影响力的原创文章，将研究结果纳入综述和临床实践指南，并为促进与慢性肾脏疾病相关的其他主题的合作研究创造了基础设施。在下一个资助期，将对慢性肾病患者诊断和管理的另一个核心问题——从血清测量中估计肾功能（肾小球滤过率，GFR）进行个体患者数据荟萃分析。具体目标是：1)建立来自广泛研究的研究人员的合作，这些研究使用碘甲酸盐的肾脏清除率来测量GFR，并将个体患者数据汇集到单个数据库中。我们已经获得了来自研究的6000名患者（31000名GFR测量）和来自临床人群的14000名患者（23000名GFR测量）的合作数据。2)开发并验证使用血清肌酐估算GFR的预测方程。使用最先进的统计和实验室方法和不同的患者群体，我们将能够在广泛的临床情况下严格评估这些方程的有效性。3)评估胱抑素作为过滤标志物，开发并验证使用血清胱抑素估计GFR的预测方程。4)使用新的方程来估计美国人口中GFR水平下降的流行程度。5)描述个体GFR估计值的精度，并在估计GFR在人群中的流行水平时纳入这些精度估计值。主要研究者和共同研究者拥有肾脏病学、临床化学、生物统计学和流行病学方面的专业知识，并在解释GFR测量、实验室方法和完成项目所需的统计技术方面拥有丰富的经验。研究结果将对慢性肾脏疾病患者的护理产生重大影响。

DESCRIPTION (provided by applicant): Chronic kidney disease is a worldwide public health problem, with increasing incidence and prevalence, poor outcomes and high cost. The overall aim of this research application is to use individual patient data meta-analysis to provide the evidence necessary to improve clinical care for patients with chronic kidney disease. The current grant period focused on pooling data from randomized clinical trials of angiotensin-converting-enzyme inhibitors to slow the progression of non-diabetic kidney disease. The conduct of this research has resulted in high impact original articles, incorporation of the findings into reviews and clinical practice guidelines, and creation of an infrastructure for stimulating collaborative research on other topics related to chronic kidney disease. In the next grant period will apply individual patient data meta-analysis to another problem central to the diagnosis and management of patients with chronic kidney disease - estimation of kidney function (glomerular filtration rate, GFR) from serum measurements. The specific aims are 1) Establish a collaboration of investigators from a wide range of studies in which GFR was measured using renal clearance of iothalamate and pool individual patient data into a single database. We have already secured collaborations to pool data on >6,000 patients (>31,000 GFR measurements) from research studies and > 14,000 patients (>23,000 GFR measurements) from clinical populations. 2) Develop and validate prediction equations using serum creatinine for estimating GFR. Using state of the art statistical and laboratory methods and diverse patient populations, we will be able to rigorously evaluate the validity of these equations in a wide range of clinical situations. 3) Assess cystatin as a filtration marker, and develop and validate prediction equations using serum cystatin for estimating GFR. 4) Use the new equations to estimate the prevalence of decreased GFR levels in the US population. 5) Characterize precision of GFR estimates in individuals and incorporate these precision estimates when estimating prevalence of GFR levels in populations. The principal investigator and co-investigators have expertise in nephrology, clinical chemistry, biostatistics, and epidemiology and have extensive experience with interpretation of GFR measurements, laboratory methods, and statistical techniques necessary to complete the project. The results will have a major impact on the care of patients with chronic kidney disease.