Acute Kidney Injury During Sickle Cell Crisis

镰状细胞危机期间的急性肾损伤

• 批准号: 9788513
• 负责人: Jeffrey D Lebensburger
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-19 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788513
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Address; Admission activity; Adult; Age; Antibiotics; Applications Grants; Benefits and Risks; Biological Availability; Biological Markers; Blood; Blood Platelets; Cells; Child; Childhood; Childhood Injury; Chronic Kidney Failure; Clinical; Cohort Studies; Collection; Complement; Consent; Creatinine; Data; Development; Diagnosis; Diagnostic; Disease; Disease Outcome; Drops; End stage renal failure; Endothelin; Endothelin-1; Endothelium; Epidemiology; Event; Frequencies; Functional disorder; Future; Goals; Heme; Hemoglobin; Hemolysis; High Prevalence; Hospitalization; Hypoxia; Incidence; Inflammatory; Injury; Intervention Trial; Kidney; Kidney Diseases; Knowledge; Laboratories; Link; Measures; Mediating; Methodology; Modeling; Monitor; Non-Steroidal Anti-Inflammatory Agents; Organ; Output; Pain; Participant; Patients; Pharmaceutical Preparations; Protocols documentation; Renal Blood Flow; Reproducibility; Research; Retrospective Studies; Risk Factors; Role; Sampling; Serum; Sickle Cell; Sickle Cell Anemia; Study models; Supportive care; Thalassemia; Therapeutic; Therapeutic Trials; Urine; Vasoconstrictor Agents; Visit; Work; acute chest syndrome; base; biomarker performance; clinical development; cohort; high risk; improved; kidney dysfunction; mortality; mortality risk; mouse model; nephrogenesis; nephrotoxicity; novel therapeutics; post gamma-globulins; prevent; programs; sickle cell crisis; urinary; vaso-occlusive pain; vasoconstriction

Project Summary/Abstract: Sickle cell disease (SCD) patients suffer from repeated episodes of vaso-occlusive pain crisis and acute chest syndrome, yet data is lacking on the impact of these clinical events on progressive end-organ damage, including kidney injury. Cell free heme and hemoglobin can be elevated during these hemolytic events. Murine models suggest that an acute increase in cell free heme and hemoglobin from a hemolytic event will mediate kidney injury. As it is well recognized the patients with sickle cell suffer from a higher prevalence of developing kidney injury, it is vital to conduct research to determine the impact of hemolysis during acute SCD crisis (pain crisis or acute chest syndrome) on the development of kidney injury. We hypothesize that during SCD crisis, kidney injury occurs and is associated with elevations in cell free heme/hemoglobin and endothelin- 1 levels. Methodology and Aims: Patients with HbSS and SB0 thalassemia (ages 6-20) admitted for SCD crisis (pain crisis or acute chest syndrome) will consent to daily first morning urine and blood collection. Urine samples will be measured for acute kidney injury biomarkers and blood will be measured for cell free heme, hemoglobin, and endothelin-1. To understand the epidemiology of SCD crisis associated AKI, we will determine the frequency of AKI as defined by the KDIGO definition (rise in serum creatinine of 0.3mg/dL or 50% from baseline, or decrease in urine output). We will perform analysis of potential risk factors for kidney injury including changes in blood counts from baseline and administration of NSAIDs or other nephrotoxic medications. Second, we still study the pathophysiology of kidney injury during SCD crisis. We will determine the associations between elevations in cell free heme/hemoglobin and endothelin-1 with the development of clinical AKI (defined by KDIGO) or subclinical AKI (elevation in urinary biomarkers without a rise in serum creatinine). Expected results: At the completion of this R03 proposal, we will establish an association linking hemolysis during SCD with the development of kidney injury. As sickle cell patients are at increased risk for mortality from chronic kidney disease, it is imperative to better understand the impact of repeated sickle cell crisis on kidney injury so that diagnostic, therapeutic, and supportive care protocols for monitoring and preventing AKI during SCD crisis can be developed.

项目概要/摘要： 镰状细胞病（SCD）患者反复发作血管闭塞性疼痛危象和急性胸部 综合征，但缺乏关于这些临床事件对进行性终末器官损伤的影响的数据， 包括肾损伤在这些溶血事件期间，游离血红素和血红蛋白可升高。 小鼠模型表明，溶血事件引起的细胞游离血红素和血红蛋白的急性增加将 介导肾损伤。众所周知，镰状细胞病患者的患病率较高， 发展肾损伤，进行研究以确定急性SCD期间溶血的影响至关重要 危机（疼痛危机或急性胸部综合征）对肾损伤的发展。我们假设， SCD危象，发生肾损伤，并与细胞游离血红素/血红蛋白和内皮素升高相关- 1级。 方法和目的：HbSS和SB 0地中海贫血患者（6 - 20岁）因SCD危象（疼痛）入院 危象或急性胸部综合征）将同意每日第一次晨尿和血液收集。尿样将 测量急性肾损伤生物标志物，并测量血液中的无细胞血红素，血红蛋白， 和内皮素-1。为了了解SCD危象相关AKI的流行病学，我们将确定 KDIGO定义的AKI频率（血清肌酐升高0.3mg/dL或50%， 基线或尿量减少）。我们将分析肾损伤的潜在风险因素 包括血细胞计数较基线的变化和NSAID或其他肾毒性药物给药 药物治疗其次，我们仍在研究SCD危象时肾损伤的病理生理学。我们将确定 细胞游离血红素/血红蛋白和内皮素-1升高与 临床AKI（由KDIGO定义）或亚临床AKI（尿液生物标志物升高，而血清 肌酸酐）。 预期结果：在完成本R03提案时，我们将建立溶血相关性 在SCD期间随着肾损伤的发展。由于镰状细胞病患者的死亡风险增加， 从慢性肾脏疾病，这是当务之急，以更好地了解反复镰状细胞危机的影响， 肾损伤使得用于监测和预防AKI诊断、治疗和支持性护理方案 在SCD危机期间可以开发。