Chronobiology and Chronopharmacology to Prevent Sickle Cell Nephropathy

预防镰状细胞肾病的时间生物学和时间药理学

基本信息

批准号：
9039658
负责人：
Jeffrey D Lebensburger
金额：
$ 19.11万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2020-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9039658
关键词：
Adherence Adolescent Age Ambulatory Blood Pressure Monitoring Antihypertensive Agents Area Biological Markers Blood Blood Pressure Blood Pressure Monitors Cardiovascular system Childhood Chronic Kidney Failure Chronobiology Circadian Rhythms Clinic Clinical Trials Cohort Studies Communities Consent Cystatins Data Development Dialysis procedure Disease Dose Eligibility Determination Enrollment Evaluation Goals Health Height High Prevalence Hour Hypertension Incidence Injury Kidney Kidney Diseases Kidney Failure LCN2 gene Laboratories Lead Link Losartan Mentors Mentorship Methodology Microalbuminuria Monitor Morbidity - disease rate Multicenter Trials National Heart, Lung, and Blood Institute Oral Organ Outcome Participant Patients Pharmaceutical Preparations Phase Pilot Projects Prevalence Procedures Progressive Disease Randomized Rare Diseases Research Risk Risk Factors Role Safety Secondary Hypertension Sickle Cell Sickle Cell Anemia Site Sleep Stroke Testing Thalassemia Therapeutic Trials Time Titrations Training Transfusion Uric Acid Urine cohort design disorder risk hydroxyurea insight mortality open label potential biomarker prevent prospective sickling therapy development treatment strategy trial design young adult

项目摘要

DESCRIPTION (provided by applicant): Significance of proposed research: Untreated hypertension and renal injury are risk factors for increased morbidity and mortality in sickle cell disease, yet early markers of progressive disease have not been identified and therapies to prevent the development of adverse cardiovascular outcomes have not been defined. Circadian blood pressure, as defined by 24 hour blood pressure monitoring, is more accurate than clinic blood pressure in defining secondary hypertension and abnormal nocturnal blood pressured dipping has been linked to progressive renal disease in other diseases. Methodology/Aims: A randomized feasibility trial of losartan will be conducted among 40 adolescent HbSS and SB0 thalassemia patients (11-19 years) with abnormal nocturnal blood pressure dipping. During this six month feasibility trial, two dosing strategies of losartan (titraed to keep BP <95th percentile vs. <75th percentile) will be analyzed for safety and effect on restoring normal circadian blood pressure. A prospective cohort study among HbSS and SB0 thalassemia patients (6-19 years) will also be conducted to evaluate the incidence of hypertension and role of monitoring potential biomarkers of kidney injury and hypertension. Cohort participants will undergo annual evaluations of hypertension and markers of kidney injury (24 hour blood pressure monitoring for participants = 11yrs; Blood: uric acid; Urine: Cystatin-c, Kim-1, NGAL, B2M). Expected Results: At the completion of the feasibility trial, vital background information will be obtained to design a definitive multicenter trial of hypertension in sickle cel disease. At the completion of the cohort study, the incidence of pediatric hypertension will be identified and the role for monitoring blood and urine biomarkers will be better understood. As therapy for patients with renal failure is dismal, it is imperative that SCD patients at risk ar identified early and that therapeutic trials are conducted that prevent progression.

描述（由申请人提供）：拟议研究的意义：未经治疗的高血压和肾损伤是镰状细胞病发病率和死亡率增加的危险因素疾病进展的早期标志物尚未确定，预防不良心血管结局的治疗方法尚未确定，通过 24 小时血压监测定义的昼夜节律血压在定义继发性心脏病方面比诊所血压更准确。高血压和夜间血压异常下降与其他疾病中的进行性肾病有关。方法/目标：将在 40 名夜间血压异常下降的青少年 HbSS 和 SB0 地中海贫血患者（11-19 岁）中进行氯沙坦的随机可行性试验。在为期六个月的可行性试验中，采用两种剂量策略（滴定以保持血压稳定）。将分析血压<95% vs. <75%）的安全性和恢复正常昼夜血压的效果。还将对 HbSS 和 SB0 地中海贫血患者（6-19 岁）进行高血压的发病率以及监测肾损伤和高血压的潜在生物标志物的作用。队列参与者将接受高血压和肾损伤标志物的年度评估（24 小时血液）。参与者的压力监测 = 11 年；血液：尿酸；尿液：胱抑素-c、Kim-1、NGAL、B2M）。队列研究完成后，将确定儿童高血压的发病率，并更好地了解监测血液和尿液生物标志物的作用。由于肾衰竭患者的治疗效果不佳，因此必须尽早识别处于危险中的 SCD 患者，并进行治疗试验以防止进展。