Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Department of Internal Medicine, Kaohsiung Municipal Cijin Hospital, Kaohsiung 805, Taiwan.
J Clin Endocrinol Metab. 2024 Jul 12;109(8):2097-2105. doi: 10.1210/clinem/dgae009.
Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear.
To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D.
Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated.
Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 μM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality.
Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D.
2 型糖尿病（T2D）是慢性肾脏病和终末期肾病（ESKD）的主要病因。三甲基胺 N-氧化物（TMAO）对 T2D 患者肾脏结局的影响尚不清楚。
检测空腹血清 TMAO 水平与 T2D 患者不良肾脏结局的相关性。
2016 年 10 月至 2020 年 6 月期间，招募 T2D 患者并每 3 个月监测一次，直至 2021 年 12 月。采用液相色谱-质谱法检测血清 TMAO 水平。主要肾脏结局为血清肌酐水平翻倍或进展为需要透析的 ESKD；次要肾脏结局为 2 年内估算肾小球滤过率快速下降 30%。还评估了全因死亡率。
在纳入的 440 例 T2D 患者中，血清 TMAO 三分位最高（≥0.88μM）的患者年龄较大，糖尿病病程较长，血尿素氮升高，估算肾小球滤过率较低。中位随访 4 年后，26 例（5.9%）患者血清肌酐水平翻倍或进展为 ESKD。经倾向评分加权后，血清 TMAO 三分位最高的患者血清肌酐水平翻倍或进展为 ESKD 的风险增加 6.45 倍，肾功能快速下降的风险增加 5.86 倍，与三分位最低的患者相比。此外，血清 TMAO 的逐步升高与全因死亡率相关。
循环 TMAO 水平升高的 T2D 患者发生血清肌酐翻倍、进展为 ESKD 和死亡的风险更高。TMAO 可能是 T2D 患者肾功能进展和死亡的潜在生物标志物。
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