Department of Endocrinology and Metabolism, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Luzhou Key Laboratory of Cardiovascular and Metabolic Diseases, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.
Adv Nutr. 2021 Jul 30;12(4):1286-1304. doi: 10.1093/advances/nmab010.
Elevated circulating trimethylamine N-oxide (TMAO) concentrations have been observed in patients with chronic kidney disease (CKD). We aimed to systematically estimate and quantify the association between TMAO concentrations and kidney function. The PubMed, EMBASE, Cochrane Library, Scopus, and Web of Science databases were systematically searched from 1995 to 1 June, 2020, for clinical studies on circulating TMAO concentrations and kidney function indicators. We used R software to conduct meta-analyses of the extracted data. A cumulative meta-analysis was applied to test whether health status affected the pooled effect value. Meta-regression and subgroup analyses were performed to identify possible sources of heterogeneity. Ultimately, we included a total of 32 eligible clinical studies involving 42,062 participants. In meta-analyses of continuous-outcome variables, advanced CKD was associated with a 67.9 μmol/L (95% CI: 52.7, 83.2; P < 0.01) increase in TMAO concentration, and subjects with high concentrations of TMAO had a 12.9 mL/(min·1.73 m2) (95% CI: -16.6, -9.14; P < 0.01) decrease in glomerular filtration rate (GFR). In meta-analyses of the correlations, TMAO was strongly inversely correlated with GFR [Fisher's z-transformed correlation coefficient (ZCOR): -0.45; 95% CI: -0.58, -0.32; P < 0.01] and positively associated with the urine albumin-to-creatinine ratio (UACR; ZCOR: 0.26; 95% CI: 0.08, 0.43; P < 0.01), serum creatinine (sCr; ZCOR: 0.43; 95% CI: 0.28, 0.58; P < 0.01), urine albumin excretion rate (UAER; ZCOR: 0.06; 95% CI: 0.04, 0.09; P < 0.01), blood urea (ZCOR: 0.50; 95% CI: 0.29, 0.72; P < 0.01), blood uric acid (ZCOR: 0.32; 95% CI: 0.25, 0.38; P < 0.01), and serum cystatin C (CysC; ZCOR: 0.47, 95% CI: 0.44, 0.51; P < 0.01). This is the first systematic review and meta-analysis to reveal a negative association between circulating TMAO concentrations and kidney function.
循环三甲基胺 N-氧化物（TMAO）浓度升高已在慢性肾脏病（CKD）患者中观察到。我们旨在系统地评估和量化 TMAO 浓度与肾功能之间的关联。从 1995 年到 2020 年 6 月 1 日，我们系统地检索了 PubMed、EMBASE、Cochrane 图书馆、Scopus 和 Web of Science 数据库，以获取关于循环 TMAO 浓度和肾功能指标的临床研究。我们使用 R 软件对提取的数据进行荟萃分析。累积荟萃分析用于检验健康状况是否影响汇总效应值。进行了荟萃回归和亚组分析，以确定可能的异质性来源。最终，我们纳入了总共 32 项符合条件的临床研究，涉及 42062 名参与者。在连续结局变量的荟萃分析中，晚期 CKD 与 TMAO 浓度升高 67.9 μmol/L（95%CI：52.7，83.2；P<0.01）相关，而 TMAO 浓度较高的患者肾小球滤过率（GFR）降低 12.9 mL/（min·1.73 m2）（95%CI：-16.6，-9.14；P<0.01）。在相关性的荟萃分析中，TMAO 与 GFR 呈强烈负相关[Fisher 转换相关系数（ZCOR）：-0.45；95%CI：-0.58，-0.32；P<0.01]，与尿白蛋白与肌酐比值（UACR；ZCOR：0.26；95%CI：0.08，0.43；P<0.01）呈正相关，与血清肌酐（sCr；ZCOR：0.43；95%CI：0.28，0.58；P<0.01）、尿白蛋白排泄率（UAER；ZCOR：0.06；95%CI：0.04，0.09；P<0.01）、血尿素氮（ZCOR：0.50；95%CI：0.29，0.72；P<0.01）、血尿酸（ZCOR：0.32；95%CI：0.25，0.38；P<0.01）和血清胱抑素 C（CysC；ZCOR：0.47，95%CI：0.44，0.51；P<0.01）呈正相关。这是第一项系统评价和荟萃分析，揭示了循环 TMAO 浓度与肾功能之间的负相关关系。
