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: 8353079
• 负责人: Julia J Scialla
• 金额: $ 17.05万
• 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/8353079
• 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. PUBLIC HEALTH RELEVANCE: This research will evaluate the role of dietary intake in early abnormalities of acid-base balance in diabetic and non-diabetic CKD, as well as its subsequent impact on clinical outcomes, including progression of kidney disease, need for dialysis, development of cardiovascular disease and mortality. This work will help justify a randomized trial of dietary modification to lower nonvolatile acid load and improve outcomes, early in CKD, prior to the development of overt acidosis.

描述（由申请人提供）：代谢性酸中毒是慢性肾脏疾病（CKD）进展的可改变的危险因素。由于饮食营养素的代谢产生的日常非易失性酸的排泄受损，因此在晚期CKD中发展。亚临床酸中毒在明显的酸中毒之前发展，也可能对临床结果产生不利影响。在临床试验中，用碱补充剂对公开和亚临床酸中毒的治疗减慢了肾脏疾病的进展，但是在某些CKD患者中，使用碱补充剂可能与无法接受的风险有关。通过饮食操纵来降低非挥发性酸负荷可能是减轻酸中毒并在CKD早期改善酸中心的互补策略。使用密集的以患者为导向的研究，我们将对患有有或没有糖尿病的早期阶段3 CKD的参与者进行详细的，直接测量饮食摄入，肾酸排泄，肾小球滤过率和亚临床酸中毒，以及在健康控制中，以确定亚细胞酸酸中毒的独立风险因素。使用这种丰富的数据来源，我们还将根据未来的研究应用来验证非挥发性酸负载的估计值。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，这是一项多样的CKD队列，并检查了其长期随访中与硬临床结果的关联。我们预计这些研究目标将在CKD中建立非易失性酸负荷作为可修改的危险因素，该危险因素可能通过直接促进亚临床上的酸中毒而产生不利影响，从定义上讲，这可以从绝大多数CKD患者中逃脱检测。此外，这项研究将在PI，Julia Scialla博士的生理和流行病学研究中提供丰富的培训经验。 Scialla博士在约翰·霍普金斯大学（Johns Hopkins University）曾在临床肾脏病和流行病学方面曾在临床肾脏病和流行病学上进行过培训，并在该领域的出版记录中构成了她的研究假设的基础。她将由经验丰富的临床医生迈尔斯·沃尔夫（Myles Wolf）博士指导 定向研究，包括生理和流行病学研究。 PI还将受益于肾脏流行病学，营养和转化研究专家的其他建议。这项受过指导的以患者为导向的研究职业发展奖将通过支持：（1）生理研究的新培训来帮助Scialla博士实现她的直接和长期目标； （2）流行病学的高级培训； （3）在酸碱稳态早期异常异常中发展科学专业知识； （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。 公共卫生相关性：这项研究将评估饮食摄入量在糖尿病和非糖尿病性CKD中酸碱早期平衡早期异常中的作用，以及其随后对临床结果的影响，包括肾脏疾病的发展，需要透析，心血管疾病和死亡率的发展。这项工作将有助于证明饮食改性的随机试验是合理的，以降低非易失性酸负荷，并在开发明显的酸中毒之前，在CKD早期改善预后。