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

• 批准号: 8507229
• 负责人: Julia J Scialla
• 金额: $ 16.94万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-15 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8507229
• 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

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脏疾病(CKD)进展的一个可改变的危险因素。它发生在晚期CKD，是由于日常饮食营养新陈代谢产生的非挥发性酸排泄受损所致。亚临床型酸中毒先于显性酸中毒发生，也可能对临床预后产生不利影响。在临床试验中，使用碱补充剂治疗显性和亚临床酸中毒都可以减缓肾脏疾病的进展，但在一些CKD患者中，碱补充剂的使用可能与不可接受的风险有关。通过饮食控制降低非挥发性酸负荷可能是一种补充策略，可以在亚临床但不明显的酸中毒出现时，减轻酸中毒并改善CKD早期的预后。我们将利用密集的以患者为中心的研究，对早期3CKD合并和不合并糖尿病的参与者以及健康对照组进行详细、直接的饮食摄入量、肾酸排泄、肾小球滤过率和亚临床酸中毒的测量，以确定亚临床酸中毒的独立危险因素。利用这一丰富的数据来源，我们还将根据未来研究应用的黄金标准来验证对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)研究的1000名参与者的非挥发性酸负荷，这是一个多样化的CKD队列研究，并检查其与长期随访的硬临床结果的关系。我们预计，这些研究目标将把非挥发性酸负荷确定为CKD的一个可改变的危险因素，它可能通过直接导致亚临床酸中毒而产生不良影响，根据定义，在绝大多数CKD患者中，亚临床酸中毒是逃脱检测的。此外，这项研究还将为PI朱莉娅·夏拉博士提供丰富的生理学和流行病学研究培训经验。夏拉博士曾在约翰霍普金斯大学接受过临床肾病学和流行病学方面的培训，并在这一领域的出版记录构成了她的研究假设的基础。她将接受迈尔斯·沃尔夫医生的指导，迈尔斯·沃尔夫医生是一位经验丰富、资金雄厚的临床医生兼科学家，拥有广泛的患者技能 以研究为导向，包括生理学和流行病学研究。肾脏流行病学、营养学和转化研究方面的专家的额外建议也将使PI受益。这一以患者为导向的指导研究职业发展奖将帮助夏拉博士实现她的近期和长期目标，方法是支持：(1)新的生理学研究培训；(2)流行病学高级培训；(3)发展早期酸碱平衡异常的科学专长；(4)生成关键的初步数据和科学合作，以促进她向研究独立性的过渡。