Biomarkers of Kidney Secretory Function for Discriminating Risk of Hyperkalemia

鉴别高钾血症风险的肾脏分泌功能生物标志物

基本信息

批准号：
10727192
负责人：
Nicholas Wettersten
金额：
$ 12.31万
依托单位：
VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10727192
关键词：
Address Albuminuria Aldosterone Ancillary Study Biological Markers Blood Blood specimen Cardiomyopathies Cessation of life Chronic Kidney Failure Cities Clinical Markers Creatinine Data Development Distal Distal convoluted renal tubule structure Dose Drug Interactions EFRAC Electrolytes Evaluation Studies Excretory function Face Fibrosis Frequencies General Population Glomerular Filtration Rate Goals Health Heart Arrest Heart failure Homeostasis Hospitalization Incidence Individual International Intervention Trial Investigation Kansas Kidney Kidney Diseases Life Link Measures Medical Methods Monitoring Clinical Trials National Heart, Lung, and Blood Institute Natriuretic Peptides Organ Participant Patients Pharmaceutical Preparations Placebos Positioning Attribute Potassium Questionnaires Randomized Renal tubule structure Research Resources Risk Risk Factors Serum Spironolactone Spottings Subgroup Symptoms Toxin Tubular formation Urine Work appropriate dose arm biomarker identification biomarker panel blood pressure intervention cardiovascular risk factor clinical practice clinical risk clinical trial enrollment cohort design follow-up glomerular filtration high risk hyperkalemia improved individual patient innovation insight kidney biopsy mortality risk novel novel marker preservation prospective randomized, clinical trials risk minimization risk mitigation risk stratification tool

项目摘要

PROJECT SUMMARY Hyperkalemia is a common and potentially life-threatening electrolyte disturbance. The risk of hyperkalemia is higher in individuals with heart failure (HF) and chronic kidney disease and with the use of certain medications, such as spironolactone. Current methods to identify individuals at increased risk of hyperkalemia are rudimentary. Potassium is primarily eliminated by the kidneys through glomerular filtration and tubular secretion, but currently only glomerular filtration is considered when evaluating risk for hyperkalemia. Novel biomarkers of kidney tubular secretion have been strongly linked with tubule fibrosis and we have recently demonstrated that a lower secretion score, a composite score from secretion biomarkers, is associated with a higher risk of incident hyperkalemia. Many medications, such as spironolactone, are eliminated through secretion. Kidney tubule secretion biomarkers have been associated with the clearance of medications dependent on kidney secretion for elimination. The Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT) trial is a multicenter international clinical trial that enrolled 3445 patients with HFpEF and randomized participants to spironolactone versus placebo. In TOPCAT, rates of hyperkalemia were 18.7% in spironolactone arm and 9.1% in the placebo arm. In this TOPCAT ancillary study, we will measure kidney tubule secretion biomarkers with the specific aims to: 1) determine if a novel panel of tubular secretion biomarkers identifies HF patients at higher risk for hyperkalemia in TOPCAT, and 2) determine if tubule secretion biomarkers are associated with improvements in heart failure symptoms and natriuretic peptide levels from spironolactone therapy among HF patients in TOPCAT. The results of this study will provide evidence for an innovative method to risk stratify individuals for risk of hyperkalemia prior to starting hyperkalemia provoking medications, and lead to a new line of investigation wherein we move secretion biomarkers from research towards clinical practice with the ultimate goal of maximizing benefits while minimizing risks of drug dosing and drug-drug interactions for secreted drugs.

项目摘要高钾血症是一种常见且潜在的威胁生命的电解质干扰。高钾血症的风险是心力衰竭（HF）和慢性肾脏疾病的患者较高，并使用某些药物，例如螺内酯。当前识别患有高钾血症风险增加的个体的方法是基本。钾主要被肾脏通过肾小球过滤消除分泌，但目前仅在评估高钾血症的风险时考虑肾小球过滤。小说肾小管分泌的生物标志物与小管纤维化有很密切的联系，我们最近有了证明较低的分泌评分是分泌生物标志物的复合分数，与发生高钾血症的较高风险。许多药物，例如螺内酯，通过分泌。肾小管分泌生物标志物与药物的清除有关取决于肾脏的分泌物。螺内酯用于心力衰竭，并保留了弹射分数（TOPCAT）试验是一项多中心国际临床试验，招募了3445例HFPEF患者和随机参与者与安慰剂与安慰剂。在TopCat中，高钾血症的率为18.7％螺内酯臂和安慰剂臂中的9.1％。在这项TopCat辅助研究中，我们将测量肾脏小管分泌生物标志物的特定目的是：1）确定一个新的管状分泌面板生物标志物鉴定出topcat中高钾血症风险较高的HF患者，2）确定小管是否是否分泌生物标志物与心力衰竭症状的改善和纳地肽有关 TOPCAT中HF患者的螺内洛氏酮治疗的水平。这项研究的结果将提供创新方法的证据，可能会在开始之前将高钾血症的风险分层的风险分层高钾血症引起药物，并导致新的调查系列，我们将分泌物移动从研究到临床实践的生物标志物，其最终目标是最大化收益最大程度地减少药物给药的风险和分泌药物的药物相互作用。