Dietary Acid Load, Subclinical Acidosis and Outcomes in Chronic Kidney Disease

膳食酸负荷、亚临床酸中毒和慢性肾病的结局

基本信息

批准号：
8661184
负责人：
Julia J Scialla
金额：
$ 1.15万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-15 至 2014-07-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8661184
关键词：
Acid-Base Equilibrium Acidosis Acids Adverse effects Affect African American Alkalies American Ammonium Ancillary Study Area Award Bicarbonates Biological Markers Buffers Cardiovascular Diseases Cardiovascular system Cations Chronic Kidney Failure Chronic Kidney Insufficiency Clinical Clinical Trials Cohort Studies Collaborations Complex Creatinine Data Data Sources Defect Detection Development Diabetes Mellitus Dialysis procedure Diet Diet Modification Dietary intake Discrimination Disease Progression End stage renal failure Epidemiologic Studies Epidemiology Event Excretory function Food Foundations Frequencies Funding Future Generations Glomerular Filtration Rate Goals Gold High Prevalence Homeostasis Hour Intake Interview Intravenous Iohexol Kidney Kidney Diseases Measurement Measures Mentored Patient-Oriented Research Career Development Award Mentors Metabolic acidosis Metabolism Nephrology Nutrient Nutritional Study Outcome Participant Patients Physiological Population Population Study Potassium Proteins Proxy Publications Questionnaires Relative (related person)Renal tubular acidosis Research Research Personnel Research Training Risk Risk Factors Role Scientist Serum Severities Sodium Bicarbonate Source Staging Supplementation Testing Tissues Training Translational Research Tubular formation Universities Urea Nitrogen Urine Wolves Work adverse outcome base clinically relevant cohort diabetic experience feeding follow-up improved inorganic phosphate modifiable risk mortality non-diabetic patient oriented patient oriented research population based randomized trial skills standard measure urinary

项目摘要

DESCRIPTION (provided by applicant): Metabolic acidosis is a modifiable risk factor for chronic kidney disease (CKD) progression. It develops in advanced CKD due to impaired excretion of the daily load of nonvolatile acid that is generated from metabolism of dietary nutrients. Subclinical acidosis develops prior to overt acidosis and may also adversely affect clinical outcomes. Treatment of both overt and subclinical acidosis with alkali supplements slows renal disease progression in clinical trials, but use of alkali supplements may be associated with unacceptable risks in some CKD patients. Lowering nonvolatile acid load through dietary manipulation may be a complementary strategy to mitigate acidosis and improve outcomes earlier in CKD when subclinical, but not overt, acidosis is present. Using intensive patient-oriented research, we will perform detailed, direct measures of dietary intake, renal acid excretion, glomerular filtration rate and subclinical acidosis in participants with early stage 3 CKD with and without diabetes, and in healthy controls, to determine independent risk factors for subclinical acidosis. Using this rich source of data, we will also validate estimates of nonvolatile acid load against gold- standard measures for future research applications. Finally, we will directly measure nonvolatile acid load in 1000 participants from the Chronic Renal Insufficiency Cohort (CRIC) study, a diverse CKD cohort, and examine its association with hard clinical outcomes over long term follow-up. We anticipate that these research aims will establish nonvolatile acid load as a modifiable risk factor in CKD that may exert adverse effects by directly contributing to subclinical acidosis, which, by definition, escapes detection in the vast majority of patients with CKD. In addition, this research will provide a rich training experience fr the PI, Dr. Julia Scialla, in physiologic and epidemiologic research. Dr. Scialla has prior trainin in clinical nephrology and epidemiology at Johns Hopkins University and a record of publication in this field which formed the basis of her research hypotheses. She will be mentored by Dr. Myles Wolf, an experienced, well-funded clinician-scientist with a broad range of skills in patient oriented research, including physiologic and epidemiologic studies. The PI will also benefit from additional advising by experts in renal epidemiology, nutrition and translational research. This Mentored Patient-Oriented Research Career Development Award will help Dr. Scialla achieve her immediate and long term goals by supporting: (1) new training in physiologic research; (2) advanced training in epidemiology; (3) the development of scientific expertise in early abnormalities of acid-base homeostasis; and (4) the generation of critical preliminary data and scientific collaborations to facilitate her transition to research independence.

描述（由申请人提供）：代谢性酸中毒是慢性肾病（CKD）进展的一个可改变的危险因素。它是由于膳食营养素代谢产生的每日负荷的非挥发性酸的排泄受损而在晚期 CKD 中发生的。亚临床酸中毒先于明显酸中毒发生，也可能对临床结果产生不利影响。在临床试验中，用碱补充剂治疗明显和亚临床酸中毒可减缓肾脏疾病的进展，但使用碱补充剂可能会导致一些 CKD 患者出现不可接受的风险。当存在亚临床但不明显的酸中毒时，通过饮食控制降低非挥发性酸负荷可能是缓解酸中毒和改善 CKD 早期结局的补充策略。通过深入的以患者为导向的研究，我们将对伴有或不伴有糖尿病的早期 3 期 CKD 参与者以及健康对照者的饮食摄入量、肾酸排泄、肾小球滤过率和亚临床酸中毒进行详细、直接的测量，以确定独立危险因素用于亚临床酸中毒。利用这一丰富的数据源，我们还将根据未来研究应用的金标准措施验证非挥发性酸负荷的估计。最后，我们将直接测量来自慢性肾功能不全队列 (CRIC) 研究（一个多样化的 CKD 队列）的 1000 名参与者的非挥发性酸负荷，并在长期随访中检查其与硬临床结果的关联。我们预计这些研究目标将确立非挥发性酸负荷作为 CKD 的可改变危险因素，可能通过直接导致亚临床酸中毒而产生不良影响，而根据定义，绝大多数 CKD 患者无法检测到亚临床酸中毒。此外，这项研究将为 PI Julia Scialla 博士提供生理学和流行病学研究方面的丰富培训经验。 Scialla 博士之前曾在约翰·霍普金斯大学接受过临床肾病学和流行病学培训，并在该领域发表过文章，这构成了她的研究假设的基础。她将接受迈尔斯·沃尔夫 (Myles Wolf) 博士的指导，迈尔斯·沃尔夫 (Myles Wolf) 是一位经验丰富、资金雄厚的临床医生兼科学家，在患者方面拥有广泛的技能。定向研究，包括生理学和流行病学研究。 PI 还将受益于肾脏流行病学、营养和转化研究专家的额外建议。这项以患者为导向的研究职业发展奖将通过支持以下方式帮助 Scialla 博士实现近期和长期目标：(1) 生理学研究方面的新培训；（二）流行病学高级培训； (3) 酸碱稳态早期异常的科学专业知识的发展； (4) 生成关键的初步数据和科学合作，以促进她向独立研究的过渡。