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（由申请方提供）：代谢性酸中毒是慢性肾脏疾病（CKD）进展的一种可改变的风险因素。由于饮食营养代谢产生的非挥发性酸的日负荷排泄受损，其在晚期CKD中发展。亚临床酸中毒发生在明显酸中毒之前，也可能对临床结局产生不利影响。在临床试验中，用碱补充剂治疗显性和亚临床酸中毒可减缓肾病进展，但在某些CKD患者中，使用碱补充剂可能与不可接受的风险相关。通过饮食控制降低非挥发性酸负荷可能是一种补充策略，以减轻酸中毒，并改善亚临床，但不明显，酸中毒时，CKD的早期结果。通过深入的以患者为导向的研究，我们将对伴有和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、肾脏酸排泄、肾小球滤过率和亚临床酸中毒进行详细、直接的测量，以确定亚临床酸中毒的独立风险因素。利用这一丰富的数据来源，我们还将验证估计的非挥发性酸负荷对黄金标准的措施，为未来的研究应用。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，并在长期随访中研究其与硬临床结局的相关性。我们预期这些研究目标将确立非挥发性酸负荷作为CKD的可改变风险因素，其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，亚临床酸中毒在绝大多数CKD患者中无法检测到。此外，本研究将为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博士曾在约翰霍普金斯大学接受过临床肾病学和流行病学的培训，并在该领域发表过论文，这是她研究假设的基础。Myles Wolf博士是一位经验丰富、资金充足的临床科学家，在患者治疗方面具有广泛的技能。 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、营养学和转化研究专家的额外建议。这个指导以患者为导向的研究职业发展奖将帮助Scialla博士实现她的近期和长期目标，支持：（1）生理学研究的新培训;（2）流行病学的高级培训;（3）发展酸碱平衡早期异常的科学专业知识;（4）研究和开发新的研究领域。以及（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。 公共卫生关系：这项研究将评估饮食摄入在糖尿病和非糖尿病CKD早期酸碱平衡异常中的作用，以及其对临床结局的后续影响，包括肾脏疾病的进展，透析需求，心血管疾病的发展和死亡率。这项工作将有助于证明饮食调整的随机试验，以降低非挥发性酸负荷和改善结果，早期慢性肾脏病，发展明显的酸中毒之前。