Risk Factors for Decline in Renal Function

描述（由申请人提供）：肾衰竭是一种危及生命和昂贵的医疗状况。终末期肾病，定义为需要慢性透析或肾移植的严重肾功能障碍，其患病率正在上升，年死亡率超过20%。不太严重的肾功能丧失也有重要的健康后果。在高危人群和普通人群中，肾功能和微量白蛋白尿轻度至中度下降是心血管疾病和死亡的重要预测指标。不良后果的风险随着肾功能的下降而增加。即使没有已知的肾功能下降的危险因素，如高血压或糖尿病，肾功能障碍也可能在几十年内缓慢发展。减缓或预防肾功能下降可能有利于影响发病率和死亡率。遗传因素、生物过程（如炎症）和环境因素（如止痛药的使用）都可能导致肾功能下降。肾素-血管紧张素系统（RAS），特别是血管紧张素II活性的升高，是肾脏病理生理的重要介质。因此，与RAS系统相关的基因可能对肾功能有重要的长期影响。慢性炎症可通过引起血管疾病和纤维化对肾脏产生不利影响。镇痛药是美国最常用的药物，慢性镇痛药的使用可能是肾功能障碍的一个重要的、可预防的原因。本研究的主要目的是在护士健康研究I和护士健康研究II两个大型女性队列中5000名参与者中，前瞻性地研究肾功能下降的危险因素，肾功能下降的定义是肾小球滤过率（使用血清肌酐）的估计下降和微量白蛋白尿的发生。储存和新收集的血液和尿液标本将允许重复测量肾功能和尿白蛋白，并允许我们检查NHS I 19年和NHS II 11年期间的变化。使用混合效应回归分析暴露组和未暴露组在长期随访期间的肾功能斜率。本研究将提供：1)肾功能下降危险因素的前瞻性数据；2)各类镇痛药安全累积剂量的阈值水平；3)以人群为基础的年轻女性和老年女性肾功能不全发生率和肾功能下降率；4)为今后肾功能衰退的长期研究提供重要资源。

DESCRIPTION (provided by applicant): Renal failure is a life-threatening and costly medical condition. End-stage renal disease, defined as severe renal dysfunction requiring chronic dialysis or kidney transplantation, is increasing in prevalence and has an annual mortality rate exceeding 20%. Less severe loss of renal function also has important health consequences. Mild to moderate reductions in renal function and microalbuminuria are important predictors of cardiovascular disease and death, in high-risk groups as well as in the general population. The risk of adverse outcomes increases with decreasing renal function. Even in the absence of known risk factors for renal function decline, such as hypertension or diabetes, kidney dysfunction may develop slowly over decades. Slowing or preventing decline in renal function may favorably impact morbidity and mortality. Genetic factors, biological processes (such as inflammation) and environmental factors (such as analgesic use) may contribute to renal function decline. Heightened activity of the renin-angiotensin system (RAS), particularly of angiotensin II, is an important mediator of renal pathophysiology. Thus, genes related to the RAS system may have important long-term effects on renal function. Chronic inflammation may adversely affect the kidney by causing vascular disease and fibrosis. Analgesics are the most commonly used drugs in the US, and chronic analgesic use may be an important, preventable cause of renal dysfunction. The primary objective of this study is to examine prospectively risk factors for renal function decline, defined as decline in estimated glomerular filtration rate (using serum creatinine) and development of microalbuminuria, among 5000 participants in two large female cohorts: the Nurses' Health Study I and the Nurses' Health Study II. Stored and newly collected blood and urine specimens will permit repeated measurements of renal function and urine albumin and will allow us to examine changes over a period of 19 years in NHS I and 11 years in NHS II. Mixed-effects regression will be used to analyze the slope of renal function in the exposed and unexposed groups during the long-term follow-up. This study will provide: 1) prospective data on risk factors for renal function decline; 2) threshold levels of safe cumulative dose of individual classes of analgesics; 3) population-based incidence rates of renal dysfunction and rate of renal function decline in younger and older women; and 4) an important resource for future long-term studies of renal function decline.