Cardiovascular effects of oral bicarbonate in CKD

口服碳酸氢盐对 CKD 的心血管作用

• 批准号: 10464574
• 负责人: Michal L Melamed
• 金额: $ 55.19万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-24 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10464574
• 关键词: Acidosis; Acids; Adverse effects; Affect; Aldosterone; Alkalies; American; Angiotensin II; Animal Model; Antihypertensive Agents; Atrial Natriuretic Factor; Bicarbonates; Biological Markers; Blood; Blood Plasma Volume; Blood Pressure; Body Weight; Brain natriuretic peptide; Cardiovascular Diseases; Cardiovascular system; Catabolism; Characteristics; Chronic Kidney Failure; Clinical; Clinical Trials; Data; Development; Diuresis; Diuretics; Double-Blind Method; End stage renal failure; Equation; Excretory function; Fluid Balance; Funding; Goals; Hormones; Human; Hypertension; Impairment; Individual; Kidney; Knowledge; Lead; Learning; Liquid substance; Measurement; Mediating; Meta-Analysis; Metabolic acidosis; Modeling; Morbidity - disease rate; Muscle; N-terminal; Natriuresis; Natriuretic Peptides; Oral; Participant; Patients; Persons; Physiological; Placebo Control; Placebos; Population; Public Health; Randomized; Rattus; Renal function; Renin; Renin-Angiotensin-Aldosterone System; Research Personnel; Safety; Sampling; Serum; Sodium; Sodium Bicarbonate; Specimen; Testing; Time; Tumor necrosis factor receptor 11b; Vascular calcification; alpha-Fetoproteins; alternative treatment; base; blood pressure elevation; bone; bone morphogenic protein; calcification; cardiovascular effects; cardiovascular risk factor; demineralization; fibroblast growth factor 23; global health; high risk; improved; indexing; inhibitor; innovation; kidney preservation; mortality; novel; particle; phase III trial; pilot trial; prevent; primary outcome; promoter; translational impact; treatment group; treatment response

Chronic kidney disease (CKD) is a major global health problem associated with high risk of morbidity and mortality. Due to impaired kidney acid excretion, up to 35% of patients with CKD develop metabolic acidosis. Such individuals are often treated with sodium bicarbonate to prevent acidosis-induced bone demineralization and muscle catabolism and preserve kidney function. However, sodium bicarbonate may also cause cardiovascular harm in two main ways. One is by causing sodium and fluid retention leading to increased blood pressure. While individual trials have not shown a substantial increase in body weight or blood pressure, a meta-analysis found that sodium bicarbonate treatment was associated with higher risks of escalating antihypertensive or diuretic therapy. High blood pressure and elevated markers of volume overload, including N-terminal pro-brain natriuretic peptide (NT-proBNP), are associated with an increased risk of cardiovascular mortality. Yet, it is unclear what effect, if any, sodium bicarbonate has on hormones that regulate sodium levels and plasma volume. A major goal of this project is to determine the effect of sodium bicarbonate treatment on levels of natriuretic peptides (NT-proBNP and atrial natriuretic peptide) and components of the renin- angiotensin-aldosterone system (renin, angiotensin II, and aldosterone) in individuals with CKD. Another major cardiovascular concern is that sodium bicarbonate may promote vascular calcification. This has been observed in animal models but has been incompletely investigated in humans. A second major goal of this project is to determine the effect of sodium bicarbonate on blood levels of inhibitors, promoters and other indices of vascular calcification (fetuin A, fibroblast growth factor-23, osteoprotegerin, bone morphogenic protein-2, calciprotein particle 2 size, and the propensity of serum to calcify [T50]) in individuals with CKD. These goals will be achieved by combining data and performing measurements using stored samples obtained from 395 participants in three randomized, double-blind, placebo-controlled, sodium bicarbonate studies conducted in the US. Measurements will be performed at baseline, 3- and 6-months. Change from baseline between the placebo and sodium bicarbonate treatment groups will be determined and mediating effects of these changes in response to treatment will be investigated using longtitudinal structural equation modeling. Although sodium bicarbonate may slow the progression of CKD, there is concern about the long-term cardiovascular safety of sodium bicarbonate. This proposal will investigate mechanisms involved with two main cardiovascular concerns, fluid retention and vascular calcification, and potentially identify individuals who may be prone to these adverse effects. These issues are large and clinically important knowledge gaps in the field. The results will have a high impact on the field and will inform clinicians and investigators about the potential for cardiovascular harm with sodium bicarbonate treatment.

慢性肾脏疾病（CKD）是一个主要的全球性健康问题，与发病率和死亡率高相关