Estimating GFR from a Panel of Endogenous Filtration Markers (Panel eGFR)

根据内源性滤过标记物组估算 GFR（eGFR 组）

• 批准号: 8550040
• 负责人: ANDREW S LEVEY
• 金额: $ 56.68万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-28 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8550040
• 关键词: Affect; Biological Assay; Biological Markers; Blood; Blood specimen; Chronic Kidney Failure; Clinical; Clinical Research; Collaborations; Creatinine; Data; Data Set; Decision Making; Development; Epidemiology; Equation; Evaluation; Filtration; Goals; Individual; Kidney Function Tests; Knowledge; Laboratories; Lead; Measures; Medicine; Modeling; Molecular Weight; Outcome; Physiological Processes; Population; Population Heterogeneity; Proteins; Public Health; Renal function; Reporting; Research; Research Design; Serum; Serum Proteins; Specimen; Statistical Methods; Subgroup; Testing; Trypsin Inhibitors; Tryptophan; United States; Update; Urea; Weight; Work; base; clinical decision-making; clinical practice; deviant; experience; improved; innovation; man; novel; novel marker; post gamma-globulins; public health relevance; public health research; tumor

DESCRIPTION (provided by applicant): Assessing kidney function is an integral part of the practice of medicine. However, even the most accurate GFR estimates based on serum creatinine and cystatin C are biased in selected populations and imprecise in all. Measured GFR is the only confirmatory test for decreased estimated GFR, but is not practical and consequently, is not performed in most clinical practice or research settings. Our long-term goal is to develop GFR estimates that are as accurate as measured GFR, requiring fewer demographic or clinical variables and only a single blood sample to assay a panel of endogenous filtration markers, which can be reported automatically by clinical laboratories for use as a confirmatory test in clinical practice and research. We think that a critical flaw in past attempts to improve GFR estimation is the search for a single ideal filtration marker. Our objective is to evaluate novel endogenous filtration markers and to identify a "GFR panel" consisting of 4-7 markers (2-4 novel and 2-3 well-established markers) for use with GFR estimating equations to report a "panel eGFR". Our central hypothesis, based on statistical concepts and confirmed by our preliminary data, is that the panel eGFR can be substantially more accurate than current GFR estimates even if each novel marker is not more accurate than creatinine or cystatin C. The rationale for including multiple markers in a panel is to diminish bias from non-correlated non-GFR determinants of each marker, reduce the need for inclusion of demographic or clinical variables, thereby increasing precision with each additional marker. The expected outcome is a GFR panel and GFR estimating equations that can be used for reporting panel eGFR that approaches the accuracy of measured GFR. Our research team, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), has extensive experience in evaluation of biomarkers, GFR estimation, and CKD epidemiology. In the current proposal, we will use specimens from 5390 subjects in 9 studies to examine 3 established (urea, creatinine and cystatin C) and 4 novel filtration markers [3 low molecular weight serum proteins: ¿-trace protein (BTP), ¿-2 microglobulin (B2M), and tumor associated trypsin inhibitor (TATI); and 1 metabolite: 2-(¿-mannopyranosyl)-L-tryptophan (MPT, also known as Tryp-Man), or another metabolite]. Our specific aims are (1) to evaluate novel endogenous filtration markers for inclusion in a panel with well-established filtration markers (GFR panel). (2) To develop GFR estimating equations for use with multiple filtration markers to report a panel eGFR. We have adequate power to test our hypotheses within studies, and within subgroups in the pooled dataset. The proposed work is highly innovative because it augments the traditional strategy of estimating GFR using a single marker, and will enable development of GFR estimates that are as accurate as measured GFR using a single blood sample. The proposed work is significant because it will facilitate development of GFR estimating equations for confirmation of decreased estimated GFR in clinical practice and research.

描述（由申请人提供）：评估肾功能是医学实践的组成部分。然而，即使是基于血清肌酐和胱抑素C的最准确的GFR估计值在选定的人群中也有偏差，并且在所有人群中都不精确。测量的GFR是估计GFR降低的唯一确证性试验，但不实用，因此在大多数临床实践或研究环境中不进行。 我们的长期目标是开发与测量的GFR一样准确的GFR估计值，需要更少的人口统计学或临床变量，并且仅需要单个血液样本来检测一组内源性滤过标志物，这些标志物可以由临床实验室自动报告，用作临床实践和研究中的确证性检测。我们认为过去的一个关键缺陷 改善GFR估计的尝试是寻找单一理想的滤过标记物。我们的目的是评价新的内源性滤过标志物，并确定由4-7个标志物（2-4个新的和2-3个已确定的标志物）组成的“GFR面板”，用于GFR估计方程，以报告“面板eGFR”。基于统计学概念并经初步数据证实，我们的中心假设是，即使每种新标志物并不比肌酐或胱抑素C更准确，但eGFR组也可以比当前GFR估计值更准确。在一组中包括多个标志物的基本原理是减少来自每个标志物的非相关非GFR决定因素的偏倚，减少纳入人口统计学或临床变量的需要，从而增加每个额外标志物的精确度。预期结果是GFR组和GFR估计方程，可用于报告接近测量GFR准确度的eGFR组。 我们的研究团队，慢性肾脏病流行病学协作组（CKD-EPI），在生物标志物评估，GFR估计和CKD流行病学方面拥有丰富的经验。在目前的建议中，我们将使用来自9项研究的5390名受试者的标本，检查3个已建立的（尿素、肌酐和胱抑素C）和4种新型滤过标志物[3种低分子量血清蛋白：<$-痕量蛋白（BTP）、<$-2微球蛋白（B2 M）和肿瘤相关胰蛋白酶抑制剂（TATI）; 1种代谢产物：2-（ω-吡喃甘露糖基）-L-色氨酸（MPT，也称为Tryp-Man）或另一种代谢物]。我们的具体目的是（1）评价新的内源性滤过标志物，以纳入具有完善滤过标志物的组（GFR组）。(2)开发GFR估计方程，用于多种滤过标志物，以报告一组eGFR。我们有足够的把握度在研究中和汇总数据集中的亚组内检验我们的假设。 拟议的工作是高度创新的，因为它增强了使用单一标志物估计GFR的传统策略，并将使GFR估计的发展与使用单一血液样本测量GFR一样准确。建议的工作是有意义的，因为它将促进GFR估计方程的发展，以确认在临床实践和研究中估计的GFR降低。