Department of Nephrology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
Sci Rep. 2017 Oct 23;7(1):13781. doi: 10.1038/s41598-017-13739-9.
Trimethylamine-N-Oxide (TMAO) is a microbiome-related metabolite that is cleared by the kidney and linked to renal function. We explored the relationship between TMAO and all-cause mortality, and determined whether this association was modified by renal function. A prospective study was performed among PREVEND participants to examine associations of plasma TMAO with all-cause mortality. After median follow-up of 8.3 years in 5,469 participants, 322 subjects died. TMAO was positively associated with age, body mass index, type 2 diabetes mellitus and inversely with estimated glomerular filtration rate (eGFRcreatcysC)(all P < 0.001). Subjects in the highest versus lowest TMAO quartile had a crude 1.86-fold higher mortality risk (P < 0.001). After adjustment for several risk factors, TMAO remained associated with all-cause mortality [HR:1.36 (95% CI, 0.97-1.91),P = 0.016]. This association was lost after further adjustment for urinary albumin excretion and eGFR [HR:1.15 (95% CI, 0.81-1.64),P = 0.22]. The association of TMAO with mortality was modified by eGFR in crude and age- and sex-adjusted analyses (interaction P = 0.002). When participants were stratified by renal function (eGFR < vs. ≥90 mL/min/1.73 m), TMAO was associated with all-cause mortality only in subjects with eGFR <90 mL/min/1.73 m [adjusted HR:1.18 (95% CI, 1.02-1.36),P = 0.023]. In conclusion, TMAO is associated with all-cause mortality, particularly in subjects with eGFR <90 mL/min/1.73 m.
三甲胺 N-氧化物（TMAO）是一种与微生物组相关的代谢物，可通过肾脏清除，与肾功能有关。我们探讨了 TMAO 与全因死亡率之间的关系，并确定这种关联是否受肾功能的影响。在 PREVEND 参与者中进行了一项前瞻性研究，以研究血浆 TMAO 与全因死亡率之间的关系。在 5469 名参与者中位随访 8.3 年后，有 322 名受试者死亡。TMAO 与年龄、体重指数、2 型糖尿病呈正相关，与估计肾小球滤过率（eGFRcreatcysC）呈负相关（均 P<0.001）。TMAO 最高四分位数与最低四分位数相比，死亡率风险增加 1.86 倍（P<0.001）。在调整了几个危险因素后，TMAO 与全因死亡率仍然相关[风险比（HR）：1.36（95%置信区间，0.97-1.91），P=0.016]。在进一步调整尿白蛋白排泄和 eGFR 后，这种相关性消失[HR：1.15（95%置信区间，0.81-1.64），P=0.22]。在 crude 和 age- 和 sex-adjusted 分析中，TMAO 与死亡率的相关性受 eGFR 调节（交互作用 P=0.002）。当根据肾功能（eGFR <与≥90 mL/min/1.73 m）对参与者进行分层时，只有 eGFR <90 mL/min/1.73 m 的受试者中 TMAO 与全因死亡率相关[调整后的 HR：1.18（95%置信区间，1.02-1.36），P=0.023]。总之，TMAO 与全因死亡率相关，特别是在 eGFR <90 mL/min/1.73 m 的受试者中。
