Dietary acid load, kidney function and disability in elderly

 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

 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