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Dietary acid load, kidney function and disability in elderly

老年人膳食酸负荷、肾功能和残疾

基本信息

批准号：
9015232
负责人：
Snezana Petrovic
金额：
$ 23.25万
依托单位：
WAKE FOREST UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-01-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9015232
关键词：
Acid-Base Equilibrium Acids Adherence Adult African American Age Age Reporting Age-Years Aging American American diet Bicarbonates Biometry Body Composition Capsicum Cardiovascular system Characteristics Chronic Kidney Failure Clinical Markers Clinical Trials Communities Consumption Controlled Clinical Trials Data Development Diabetes Mellitus Diet Disease Disease Progression Double-Blind Method Elderly Elderly man Elderly woman Ensure Environment Epidemiology Excretory function Exercise Food Fracture Future Gender Geriatrics Health Heart High Prevalence Homeostasis Hypertension Impairment Incidence Intervention Kidney Kidney Diseases Life Link Maintenance Metabolic Metabolic Pathway Metabolic acidosis Methods Monitor Musculoskeletal Nephrology Neurologic Oral Organ Osteopenia Participant Patients Physical Function Placebo Control Placebos Population Prevention Prevention strategy Production Race Randomized Recruitment Activity Regulation Renal function Reporting Research Risk Schedule Scheme Serum Smoking Status Staging Structure Supplementation System Testing Tissues Urine age group age related base bone mass cohort design disability falls follow-up forest frailty fruits and vegetables functional decline functional outcomes health data improved instrumental activity of daily living lean body mass metabolomics muscle form novel pilot trial prevent response sarcopenia success therapy development treatment strategy western diet

项目摘要

DESCRIPTION (provided by applicant): We propose a double-blind, placebo-controlled clinical trial to determine the feasibility of a new intervention for disability prevention. It focses on the interaction of impaired acid-base balance and the aging kidney and their link to functional outcomes, specifically in the elderly who are at risk for developing disability. Disability and fralty strongly correlate with declining kidney function and chronic kidney disease (CKD), which is highly prevalent in the elderly and associates with sarcopenia, osteopenia, fractures and falls. Low serum bicarbonate and impaired acid-base homeostasis, also common in CKD, contribute significantly to functional decline. Moreover, the adaptive response of the kidney to prevent metabolic acidosis facilitates CKD progression, creating a vicious cycle in which declining kidney function impairs acid-base balance, and impaired acid-base balance facilitates kidney functional decline. This relationship is amplified by high dietary acid load of the Western diet. Our approach is based on studies indicating that maintenance of serum bicarbonate at 24meq/L with oral bicarbonate supplementation slows CKD progression in adults with CKD and may have positive effects on functional outcomes. Our preliminary data from the Health Aging and Body Composition cohort >69, suggest that lower dietary acid load associates with stable kidney function over a 7 year follow up. Preliminary metabolomics analysis indicates that it is feasible t define specific urine metabolites that correlate with lower consumption of base-forming fruits and vegetables, higher rates of kidney acid excretion and early CKD and its progression. We hypothesize that decreasing metabolic acid production by titrating dietary acid load may be an effective strategy to ameliorate the age-related decline in kidney function, decrease loss of lean body mass, and preserve physical function/ameliorate disability. The objectives of the current pilot are to establish the feasibility of this approach in the elderly at risk for disability. We propose to: (Aim1) recruit and randomize 80 elderly men and women to oral bicarbonate intervention aimed at titrating net dietary acid load or placebo to determine the feasibility of achieving a ~ 50% reduction at 6-months in net acid excretion; (Aim2) ascertain recruitment yields, compliance with the intervention and its sustainability, and determine variability and longitudinal correlations of the parameters related to potential endpoints for a full-scale clinica trial (kidney function, lean body mass and functional outcomes); (Aim3) explore the feasibility of using metabolomics to detect effects of lowering dietary acid load on kidney function; metabolomics will also provide clues about the metabolic pathways activated/deactivated during the intervention. This proposal therefore, describes a step towards a new strategy for prevention/treatment of mobility disability. Given the high prevalence of disability, potential impact of new treatment strategies cannot be overstated. Our focus on the manipulation of acid-base status is novel, has not been tested in elderly at risk for disability, and our team is carefuly selected to ensure successful design and completion of the pilot trial