RATIONALE & OBJECTIVE Metabolic acidosis associated with chronic kidney disease (CKD) may contribute to muscle dysfunction and bone disease. We aimed to test whether treatment with sodium bicarbonate improves muscle and bone outcomes. STUDY DESIGN Multicenter, randomized, placebo-controlled, clinical trial. SETTING & PARTICIPANTS 149 patients with CKD stages 3 and 4 between July 2011 and April 2016 at 3 centers in Cleveland, OH, and the Bronx, NY. INTERVENTION Sodium bicarbonate (0.4 mEq per kg of ideal body weight per day) (n=74) or identical-appearing placebo (n=75). OUTCOMES Dual primary outcomes were muscle function assessed using sit-to-stand test and bone mineral density. Muscle biopsies were performed at baseline and 2 months. Participants were seen at baseline and 2, 6, 12, and 24 months. RESULTS Mean baseline serum bicarbonate level was 24.0±2.2 (SD) mEq/L and mean baseline estimated glomerular filtration rate was 36.3±11.2mL/min/1.73m2. Baseline characteristics did not differ between groups. Mean serum bicarbonate levels in the intervention arm during follow-up were 26.4±2.2, 25.5±2.3, 25.6±2.6, and 24.4±2.8 mEq/L (at 2, 6, 12, and 24 months). These were significantly higher than in the placebo group (P<0.001). Compared to the placebo group, participants randomly assigned to sodium bicarbonate treatment had no significant differences in sit-to-stand time (5 repetitions: P=0.1; and 10 repetitions P=0.07) or bone mineral density (P=0.3). Sodium bicarbonate treatment caused a decrease in serum potassium levels that was of borderline statistical significance (P=0.05). There were no significant differences in estimated glomerular filtration rates, blood pressure, weight, serious adverse events, or levels of muscle gene expression between the randomly assigned groups. LIMITATIONS Initial mean serum bicarbonate level was in the normal range. CONCLUSIONS Sodium bicarbonate therapy in patients with CKD stages 3 and 4 significantly increases serum bicarbonate and decreases potassium levels. No differences were found in muscle function or bone mineral density between the randomly assigned groups. Larger trials are required to evaluate effects on kidney function. FUNDING National Institutes of Health grant. TRIAL REGISTRATION Registered at ClinicalTrials.gov with study number NCT01452412.

中文翻译：

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碳酸氢钠在CKD阶段3和4中的作用：一项随机，安慰剂对照的多中心临床试验。

理由和目标与慢性肾脏病（CKD）相关的代谢性酸中毒可能会导致肌肉功能障碍和骨骼疾病。我们旨在测试用碳酸氢钠治疗是否可以改善肌肉和骨骼的结局。研究设计多中心，随机，安慰剂对照的临床试验。地点与参与者2011年7月至2016年4月之间，在俄亥俄州克利夫兰和纽约州布朗克斯的3个中心共有149例CKD 3和4期患者。干预碳酸氢钠（0.4 mEq / kg每天理想体重）（n = 74）或外观相同的安慰剂（n = 75）。结局双主要结局是通过坐立测验和骨矿物质密度评估肌肉功能。在基线和2个月时进行肌肉活检。在基线和第2、6、12和24个月时观察到参与者。结果平均基线碳酸氢盐水平为24.0±2.2（SD）mEq / L，平均基线估计肾小球滤过率为36.3±11.2mL / min / 1.73m2。各组之间的基线特征没有差异。随访期间，干预组的平均血清碳酸氢盐水平为26.4±2.2、25.5±2.3、25.6±2.6和24.4±2.8 mEq / L（在2、6、12和24个月时）。这些显着高于安慰剂组（P <0.001）。与安慰剂组相比，随机分配碳酸氢钠治疗的参与者的站立时间（5次重复：P = 0.1； 10次重复P = 0.07）或骨矿物质密度（P = 0.3）没有显着差异。碳酸氢钠治疗导致血清钾水平降低，这在统计学上具有临界意义（P = 0.05）。在随机分配的组之间，估计的肾小球滤过率，血压，体重，严重不良事件或肌肉基因表达水平无显着差异。局限性最初的平均血清碳酸氢盐水平在正常范围内。结论CKD 3和4期患者的碳酸氢钠治疗可显着增加血清碳酸氢盐并降低钾水平。在随机分配的组之间，肌肉功能或骨矿物质密度没有发现差异。需要更大的试验来评估对肾功能的影响。资助国立卫生研究院拨款。试验注册在ClinicalTrials.gov上注册，研究编号NCT01452412。或随机分配的组之间的肌肉基因表达水平。局限性最初的平均血清碳酸氢盐水平在正常范围内。结论CKD 3和4期患者的碳酸氢钠治疗可显着增加血清碳酸氢盐并降低钾水平。在随机分配的组之间，肌肉功能或骨矿物质密度没有发现差异。需要更大的试验来评估对肾功能的影响。资助国立卫生研究院拨款。试验注册在ClinicalTrials.gov上注册，研究编号NCT01452412。或随机分配的组之间的肌肉基因表达水平。局限性最初的平均血清碳酸氢盐水平在正常范围内。结论CKD 3和4期患者的碳酸氢钠治疗可显着增加血清碳酸氢盐并降低钾水平。在随机分配的组之间，肌肉功能或骨矿物质密度没有发现差异。需要更大的试验来评估对肾功能的影响。资助国立卫生研究院拨款。试验注册在ClinicalTrials.gov上注册，研究编号NCT01452412。在随机分配的组之间，肌肉功能或骨矿物质密度没有发现差异。需要更大的试验来评估对肾功能的影响。资助国立卫生研究院拨款。试验注册在ClinicalTrials.gov上注册，研究编号NCT01452412。在随机分配的组之间，肌肉功能或骨矿物质密度没有发现差异。需要更大的试验来评估对肾功能的影响。资助国立卫生研究院拨款。试验注册在ClinicalTrials.gov上注册，研究编号NCT01452412。