α-酮酸对慢性肾脏病患者的附加作用: 一项随机对照试验的系统评价和meta分析

doi:10.5246/jcps.2017.01.006

摘要/Abstract

摘要：

α-酮酸广泛应用于慢性肾脏病中, 但其有效性始终存在争议。本研究便旨在评价其有效性。首先我们检索PubMed, EMBASE, Cochrane Library、CENTRAL、CNKI和万方数据库, 检索时限均从建库至2016-5-31。纳入α-酮酸联合低蛋白饮食与低蛋白饮食对照的RCT, 由2位研究者独立筛选文献、提取资料并进行文献质量评价和纳入研究的偏倚风险评估, 采用Rev Man 5.3软件进行Meta分析和敏感性分析。据统计, 共纳入21篇RCT, 1448例研究对象, 其中单用低蛋白饮食治疗者722例, α-酮酸联合低蛋白饮食干预的患者726例。与低蛋白饮食组相比, α-酮酸联合低蛋白饮食能降低血清肌酐(95% CI, 0.46–0.96; P<0.00001), 总胆固醇(95% CI , 0.24–0.77; P = 0.02), 总甘油三酯(95% CI, 0.28–0.83; P = 0.02), 低密度脂蛋白(95% CI, 0.12–0.54; P = 0.31)并且增加高密度脂蛋白(95% CI, –1.73–0.07; P<0.00001); 此外, 还能降低血P^3– (95% CI, 0.90–1.26; P<0.00001) 以及血甲状旁腺激素水平(95% CI, 0.70–1.21; P = 0.007)。没有高血钙等其他药物不良反应或毒性事件被报道。但荟萃分析存在较大的异质性。低质量的证据表明α-酮酸可能具有附加的改善肾脏功能、调节脂质代谢和钙磷代谢的作用。但鉴于研究较大的异质性与处方α-酮酸的成本和患者依从性问题, α-酮酸在CKD管理中的地位仍需要大规模、高质量的随机对照研究进行证实。

关键词: α-酮酸, 慢性肾脏病, 系统评价, Meta分析, RCT

Abstract:

α-Ketoacids (KAs) are widely used in chronic kidney disease (CKD), but their efficacy is not clear. Therefore, we conducted a systematic review of the benefits of KAs. Two reviewers independently searched MEDLINE, EMBASE, the Cochrane library (http://www.cochrane.org), CNKI, and Wan Fang databases from inception to May 31, 2016 for randomized controlled trials (RCTs) comparing KAs plus low protein diet (LPD) with LPD only on CKD patients. Statistical analyses were performed using both a random effects model and a fixed effects model with Rev Man 5.3, followed by sensitivity analysis. We identified 21 randomized controlled trials that enrolled a total of 1448 patients. 726 had received LPD plus KAs and 722 had received only LPD. Compared with simply using of LPD, combining with KAs could decrease serum creatinine (95% CI, 0.46–0.96; P<0.00001), serum cholesterol (95% CI, 0.24–0.77; P = 0.02), serum LDL cholesterol (95% CI, 0.12–0.54; P = 0.31), and serum triglyceride (95% CI, 0.28–0.83; P = 0.02) while increasing serum HDL cholesterol (95% CI, -1.73–0.07; P<0.00001). Likewise, a decrease in P^3–(95% CI, 0.90–1.26; P<0.00001) and PTH (95% CI, 0.70–1.21; P = 0.007) were observed. No hypercalcemia and other ARD or toxicity was reported, which indicated the safety of KAs. Nevertheless, the studies were pooled with considerable heterogeneity. In patients with CKD, there was low-quality evidence suggesting that KAs may perform an additive effect on the improvement of renal function, lipid profile, as well as the correction of calcium-phosphate metabolism disorders. On account of the considerable heterogeneity of the meta-analysis and the costly price and adherence of KAs administration, KAs’ roles in the management of mild or moderate CKD patients may need more RCTs of large scale and high quality to confirm.

Key words: α-Ketoacids, Chronic kidney disease, Systematic review, Meta-analysis, RCTs

中图分类号:

R954

Supporting:

韩茹, 安雅晶, 赵荣生. α-酮酸对慢性肾脏病患者的附加作用: 一项随机对照试验的系统评价和meta分析[J]. 中国药学(英文版), 2017, 26(1): 63-75.

Ru Han, Yajing An, Rongsheng Zhao. Additive effect of α-ketoacids in chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(1): 63-75.

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