Racial Differences in Phosphorus Metabolism in Health and in Kidney Disease

健康和肾脏疾病中磷代谢的种族差异

• 批准号: 7666183
• 负责人: Orlando M Gutierrez
• 金额: $ 13.72万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7666183
• 关键词: Accounting; Calcium; Cardiovascular Diseases; Cardiovascular system; Chronic Kidney Failure; Clinical Investigator; Clinical Research; Clinical Trials; Cyclic AMP; Data; Diabetes Mellitus; Dialysis procedure; Diet; Dietary intake; Disease Outcome; Disease Progression; End stage renal failure; Ensure; Epidemic; Excretory function; General Hospitals; Glomerular Filtration Rate; Goals; Health; Healthcare; High Prevalence; Hormonal; Hormones; Human; Hypertension; Individual; Infusion procedures; Intake; Internal Medicine; Investigation; Kidney; Kidney Diseases; Kidney Failure; Link; Massachusetts; Master' s Degree; Measures; Mediating; Mediator of activation protein; Mentored Patient-Oriented Research Career Development Award; Mentors; Metabolism; Nephrology; Nephrons; Oral; Parathyroid Hormones; Physiological; Poverty; Prevalence; Public Health; Race; Relative (related person); Research; Research Personnel; Research Training; Residencies; Resistance; Risk Factors; Serum; Staging; Stimulus; Testing; Time; Training; Universities; Vitamin D; absorption; base; career development; feeding; fibroblast growth factor 23; hormone regulation; human PTH protein; improved; inorganic phosphate; insight; medical schools; mortality; new therapeutic target; novel; patient oriented; phosphorus metabolism; programs; public health relevance; racial difference; response; skills; success; training project; urinary

DESCRIPTION (provided by applicant): Candidate: Orlando Gutierrez received his MD from the University of Toledo, and completed his Internal Medicine Residency at the Massachusetts General Hospital. He is currently a clinical and research fellow in nephrology at MGH, and a candidate for a Master's degree in human physiological investigation from Harvard Medical School. Mentor: Dr. David Nathan is a renowned clinical investigator who has trained numerous investigators in patient-oriented clinical research. Dr. Nathan will ensure the success of Dr. Gutierrez's research training, project, and overall career development. Research: Blacks with chronic kidney disease (CKD) progress to end stage renal disease and develop cardiovascular disease (CVD) more rapidly than Whites. The mechanisms that underlie these disparities remain elusive. Hyperphosphatemia is linked with both accelerated kidney and CVD progression. Parathyroid hormone (PTH) and Fibroblast Growth Factor 23 (FGF-23) are the primary hormones that regulate serum phosphate (Pi) levels. Preliminary data from our group indicate that Blacks with CKD have a higher prevalence of hyperphosphatemia than Whites at all levels of glomerular filtration rate despite higher PTH levels, suggesting that Blacks have impaired Pi excreting capacity. Impaired Pi excretion may represent a novel risk factor for faster kidney and CV disease progression in Blacks. However, no studies have examined differences in Pi handling by race. For Aim 1, we will examine racial differences in gut and renal Pi handling by measuring (1) gut Pi absorption after a fixed Pi meal and (2) dynamic changes in urinary Pi excretion in response to oral Pi loading in healthy Blacks vs. Whites. For Aim 2, we will examine racial differences in hormonal reguation of Pi metabolism by comparing (1) the phosphaturic effect of synthetic PTH infusion and (2) dynamic changes in FGF-23 levels after oral Pi loading in healthy Blacks vs. Whites. For Aim 3, we will examine racial differences in Pi handling in CKD by measuring urinary Pi excretion in response to dietary Pi loading in Blacks vs. Whites with CKD. We will then compare any differences in CKD to those seen in healthy individuals. We believe the results of these studies will provide critical new insights into racial differences in Pi metabolism that may help elucidate racial disparities in CKD outcomes with important public health implications. A K23 award will allow Dr. Gutierrez to attain new skills in clinical investigation and develop into an independent clinical investigator. PUBLIC HEALTH RELEVANCE: We believe the results of these studies will provide critical new insights into racial differences in serum phosphate metabolism that may help elucidate racial disparities in chronic kidney disease outcomes with important public health implications.

描述（由申请人提供）： 候选人：奥兰多·古铁雷斯（Orlando Gutierrez）从托莱多大学获得了医学博士学位，并在马萨诸塞州综合医院完成了内科住院医师。他目前是MGH肾脏科学的临床和研究研究员，也是哈佛医学院的人类生理研究硕士学位的候选人。导师：David Nathan博士是一位著名的临床研究者，他曾培训了许多研究人员，以患者为导向的临床研究。内森博士将确保古铁雷斯博士的研究培训，项目和整体职业发展的成功。研究：患有慢性肾脏疾病（CKD）的黑人比白人更快地发展为末期肾脏疾病并发展心血管疾病（CVD）。这些差异基于这些差异的机制仍然难以捉摸。高磷酸血症与加速肾脏和CVD进展有关。甲状旁腺激素（PTH）和成纤维细胞生长因子23（FGF-23）是调节血清磷酸盐（PI）水平的主要激素。来自我们小组的初步数据表明，CKD的黑人在所有水平的肾小球滤过率上，尽管PTH水平较高，但患有CKD的黑人患者的患病率高于白人，这表明黑人的PI排泄能力受损。 PI排泄受损可能代表了黑人更快的肾脏和CV疾病进展的新风险因素。但是，没有研究检查种族处理PI处理的差异。对于AIM 1，我们将通过测量（1）固定PI粉后（1）肠道PI吸收的肠道和肾脏PI处理中的种族差异，以及（2）尿液PI排泄的动态变化，以响应健康黑人与白人的口服PI负载，以响应口服PI。对于AIM 2，我们将通过比较（1）合成PTH输注的磷酸作用和（2）健康黑人与白人的口服PI负载后FGF-23水平的动态变化来检查PI代谢的激素差异。对于AIM 3，我们将通过测量尿液PI排泄来检查CKD中PI处理中的种族差异，以响应黑人与白人使用CKD的饮食PI负载。然后，我们将将CKD的任何差异与在健康个体中看到的差异进行比较。我们认为，这些研究的结果将为PI代谢的种族差异提供关键的新见解，这可能有助于阐明具有重要公共卫生影响的CKD结果中的种族差异。 K23奖将使Gutierrez博士能够获得临床研究的新技能，并发展成为独立的临床研究者。 公共卫生相关性：我们相信这些研究的结果将为血清磷酸盐代谢的种族差异提供关键的新见解，这可能有助于阐明具有重要公共卫生意义的慢性肾脏疾病成果中的种族差异。