Dysregulated Mineral Metabolism in Acute Kidney Injury

急性肾损伤时矿物质代谢失调

基本信息

批准号：
8702918
负责人：
David Evan Leaf
金额：
$ 6.37万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-30 至 2015-06-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8702918
关键词：
Acute Renal Failure with Renal Papillary Necrosis Affect Animals Attenuated Biochemical Markers Biological Markers Blood Calcitriol Cardiac Surgery procedures Cardiovascular Diseases Chronic Kidney Failure Clinical Cohort Studies Critical Illness Data Development Double-Blind Method End stage renal failure Enrollment Functional disorder Goals Host Defense Hour Human Human Cell Line Hyperparathyroidism Hypocalcemia result Immune Immune system Immunity Infection Inflammation Inflammatory Injury Interleukin-6 Kidney Measures Metabolism Minerals Modeling Natural Immunity Observational Study Outcome Participant Patients Pharmaceutical Preparations Physiological Pilot Projects Placebo Control Placebos Plasma Play Postoperative Period Production Proteinuria Randomized Randomized Controlled Trials Renin-Angiotensin System Reporting Research Design Risk Risk Factors Role Sampling Sepsis Septic Shock Testing Urine Vitamin D Vitamin D Deficiency adverse outcome cathelicidin cathelicidin antimicrobial peptide cytokine fibroblast growth factor 23 improved inflammatory marker mortality novel public health relevance rat KIM-1 protein urinary

项目摘要

DESCRIPTION (provided by applicant): Dysregulated mineral metabolism is a universal feature of advanced chronic kidney disease (CKD) and is strongly associated with an increased burden of cardiovascular disease. In acute kidney injury (AKI), in contrast, relatively little is known about mineral metabolism. Our preliminary data indicate that many of the abnormalities in mineral metabolism that are observed in CKD, such as hypocalcemia, hyperphosphatemia, hyperparathyroidism, elevated Fibroblast Growth Factor-23 (FGF23), and vitamin D deficiency are also observed in AKI. Whether these derangements in mineral metabolism are associated with adverse outcomes in AKI, as they are in CKD, and whether intervening on them might impact clinical outcomes, has not been rigorously studied. We propose to study derangements in mineral metabolism in two groups of patients with AKI: AKI resulting from sepsis and AKI occurring after cardiac surgery. Among patients with sepsis and AKI, vitamin D deficiency is common and is strongly associated with adverse outcomes. Vitamin D has important effects on immunity and inflammation. We propose a pilot study evaluating the effects of activated vitamin D on immune, inflammatory, and renal injury biomarkers among critically-ill patients with sepsis with or without AKI. We will enroll 60 patients and randomly assign them 1:1 to receive a single administration of calcitriol 2mcg IV versus placebo. Participants with AKI will be stratified in equal numbers into the two groups. We will collect plasma and urine at 0, 6, 24, and 48 hours after study drug administration. We will test the hypotheses that calcitriol administration, compared to placebo, will result in favorable effects on markers of innate immunity and inflammation, identified by an increase in plasma cathelicidin and a decrease in plasma IL-6 levels, and will protect against AKI, identified by a decrease in urinary KIM-1 levels. Elevated FGF23 levels are associated with increased mortality in CKD and ESRD but have not been studied in detail in AKI. We propose to study FGF23 as a biomarker of adverse outcomes in cardiac surgery-associated AKI. We will use a case-cohort study design, comparing FGF23 levels among cases (those who develop AKI after cardiac surgery) to non- cases. We will test the hypothesis that elevated plasma FGF23 levels are an independent predictor of the composite clinical outcome of mortality or sustained kidney injury 90 days following cardiac surgery.

描述（由申请人提供）：矿物质代谢失调是晚期慢性肾脏疾病（CKD）的普遍特征，并且与心血管疾病的负担增加密切相关。相比之下，在急性肾脏损伤（AKI）中，关于矿物质的代谢知之甚少。我们的初步数据表明，在CKD中观察到的矿物质代谢中的许多异常，例如低钙血症，高磷酸血症，高甲状腺功能亢进症，成纤维细胞生长因子23（FGF23）和维生素D缺乏症在AKI中也被观察到。矿物质代谢中的这些危险是否与CKD中的AKI不良结果有关，并且干预是否会影响临床结果，并未受到严格的研究。我们建议研究两组AKI患者的矿物质代谢的危险：脓毒症和AKI导致心脏手术后发生的AKI。在败血症和AKI患者中，维生素D缺乏症很常见，并且与不良结局密切相关。维生素D对免疫和炎症具有重要影响。我们提出了一项试点研究，以评估活化的维生素D对具有或没有AKI的脓毒症患者的免疫，炎症和肾脏损伤生物标志物的影响。我们将招募60名患者，并随机分配1：1，以接收钙三醇2MCG IV与安慰剂的单一给药。具有AKI的参与者将相等地分为两组。在学习药物管理后，我们将在0、6、24和48小时收集血浆和尿液。我们将测试与安慰剂相比，与安慰剂相比，骨化三醇给药的假设将对先天免疫和炎症标记产生有利的影响，这通过血浆cathelicidin的增加而确定，血浆IL-6水平降低，并将预防AKI降低AKI，并通过静脉KIM-1水平的降低来鉴定出AKI。 FGF23水平升高与CKD和ESRD的死亡率升高有关，但尚未在AKI中进行详细研究。我们建议将FGF23研究为心脏外科相关的AKI的不良结果的生物标志物。我们将使用病例研究设计设计，比较病例（心脏手术后发生AKI）之间的FGF23水平与非病例。我们将检验以下假设：升高血浆FGF23水平是心脏手术后90天死亡率或持续肾损伤的复合临床结果的独立预测指标。