Identifying Risk Factors and Improving Risk Assessment for Nephrolithiasis

识别肾结石的风险因素并改进风险评估

• 批准号: 8437758
• 负责人: ERIC N TAYLOR
• 金额: $ 28.11万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-22 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8437758
• 关键词: 1,25 (OH) vitamin D; 25-hydroxyvitamin D; Adherence; Animals; Binding; Biological Availability; Biological Markers; Blood specimen; Body Size; Bone Density; Calcium; Calcium Oxalate; Child; Citrates; Clinic; Cohort Studies; Collection; Comorbidity; Conflict (Psychology); Creatinine; Defect; Diet; Dietary Calcium; Dietary Factors; Dietary intake; Equilibrium; Event; Excretory function; Fasting; Fracture; Health Professional; Henle' s loop; Hip Fractures; Homeostasis; Hormones; Hour; Human; Individual; Intervention; Kidney; Kidney Calculi; Lead; Leptin; Life; Link; Maine; Measures; Medical; Medical center; Metabolic; Mus; Nature; Nephrolithiasis; Nested Case-Control Study; Normal Range; Nurses' Health Study; Pain; Parathyroid gland; Participant; Patients; Phosphorus; Plasma; Postmenopause; Prevention strategy; Public Health; Recording of previous events; Recurrence; Reporting; Research; Risk; Risk Assessment; Risk Factors; Sampling; Sodium; Spottings; Supplementation; Time; Trauma; Urine; Vitamin D; Woman; bone; calcium intake; calcium phosphate; clinical care; compliance behavior; data modeling; design; effective therapy; fibroblast growth factor 23; follow-up; high risk; human data; improved; interstitial; leptin receptor; men; prevent; prospective; public health relevance; response; screening; skeletal; treatment strategy; urinary; wrist fracture

DESCRIPTION (provided by applicant): Kidney stones are common, costly, and painful. We propose to delineate kidney stone (KS) risk factors that may lead to new treatment or prevention strategies (Aim 1), to identify a serious preventable co-morbidity associated with KS (Aim 2), and to provide a new way to assess response to existing therapies (Aim 3). Higher urine calcium is a major risk factor for KS. Existing human studies of calcium-phosphorus regulatory hormones on KS formation are widely cited and substantially impact clinical care and KS research. However, these studies are limited by small size, conflicting results, and/or cross-sectional design. In Aim 1, we will examine associations between plasma biomarkers of calcium-phosphorus homeostasis and incident KS in prospective nested case-control studies of 2,400 participants using stored blood samples in the Health Professionals Follow-up Study and the Nurses' Health Study (NHS) II. Animal KS models and data from human KS formers suggest a metabolic abnormality shared by bone and kidney that decreases bone mineral density via a combination of increased mobilization of skeletal calcium and increased loss of urine calcium. Higher urine calcium is associated with lower bone mineral density in KS formers. Previous reports, albeit small and unadjusted for dietary intakes, suggest that individuals with KS have higher risk of bone fracture. A link between KS history and hip fracture risk, if established, woul suggest routine screening for low bone mineral density in women with KS, which could prevent many cases of hip fracture. In Aim 2, we will conduct a prospective cohort study in > 75,000 postmenopausal NHS I participants examining associations between KS history and subsequent risk of low to moderate trauma hip fracture. In NHS I and other cohort studies there are no definitive associations between intakes of calcium and bone fracture. However, KS formers have lower dietary calcium and higher urinary calcium than individuals without KS. Thus, in the 5% of women with KS, higher intakes of calcium may mitigate negative calcium balance and reduce subsequent fracture risk. We also will determine whether higher calcium intake is independently associated with decreased risk of low or moderate trauma fracture in women with a history of KS. Because effective treatments for kidney stone recurrence already exist, we also aim to provide a new way of improving adherence to proven prevention strategies. In Aim 3, we will determine whether spot urine samples scaled to 24-hour urine creatinine can reliably substitute for repeat 24-hour urine quantifications of lithogenic factors i 80 free-living individuals from the Maine Medical Center KS clinic.

描述（由申请人提供）：肾结石很常见，昂贵且痛苦。我们建议描述可能导致新的治疗或预防策略（AIM 1）的肾结石（KS）危险因素（AIM 1），以确定与KS相关的严重可预防的合并症（AIM 2），并提供一种评估对现有疗法反应的新方法（AIM 3）。较高的尿钙是KS的主要危险因素。对KS形成的钙磷调节激素的现有人类研究被广泛引用，并显着影响临床护理和KS研究。但是，这些研究受到小规模，冲突结果和/或横截面设计的限制。在AIM 1中，我们将研究在卫生专业人员随访研究中使用储存的血液样本和护士健康研究（NHS）II中使用存储的血液样本对2400名参与者的预期嵌套病例对照研究中的血浆生物标志物与入射KS之间的关联。动物KS模型和来自人类KS谱系的数据表明，骨骼和肾脏共有的代谢异常，通过增加骨骼钙的动员和增加尿液钙的损失来降低骨矿物质密度。较高的尿液钙与KS形成器中较低的骨矿物质密度有关。以前的报道，尽管饮食摄入量很小且未经调整，但表明患有KS的人患骨骼骨折的风险更高。如果确定，KS病史与髋部骨折风险之间的联系会表明，常规筛选KS女性的骨矿物质密度低，这可以防止许多髋部骨折病例。在AIM 2中，我们将在> 75,000个绝经后NHS I参与者中进行一项前瞻性队列研究，以检查KS历史和随后发生低至中度创伤髋部骨折的风险。在NHS I和其他队列研究中，钙和骨断裂的摄入量之间没有明确的关联。但是，KS的饮食钙比没有KS的个体较低。因此，在5％的KS女性中，较高的钙摄入量可能减轻负钙平衡并降低随后的骨折风险。我们还将确定较高的钙摄入量是否与患有KS病史的女性低或中度创伤骨折的风险降低有关。由于已经存在对肾结石复发的有效治疗方法，因此我们还旨在提供一种新的方法来改善依从性的预防策略。在AIM 3中，我们将确定是否缩放到24小时的尿液肌酐可以可靠地代替岩性因子的重复24小时尿液量化I 80个自由生活的人，来自缅因州医学中心KS诊所。