Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Vth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Center Mannheim, University of Heidelberg, Mannheim, Germany.
Am J Clin Nutr. 2021 Oct 4;114(4):1505-1517. doi: 10.1093/ajcn/nqab185.
It is unknown whether meat intake is beneficial for long-term patient and graft survival in kidney transplant recipients (KTR).
We first investigated the association of the previously described meat intake biomarkers 1-methylhistidine and 3-methylhistidine with intake of white and red meat as estimated from a validated food frequency questionnaire (FFQ). Second, we investigated the association of the meat intake biomarkers with long-term outcomes in KTR.
We measured 24-h urinary excretion of 1-methylhistidine and 3-methylhistidine by validated assays in a cohort of 678 clinically stable KTR. Cross-sectional associations were assessed by linear regression. We used Cox regression analyses to prospectively study associations of log2-transformed biomarkers with mortality and graft failure.
Urinary 1-methylhistidine and 3-methylhistidine excretion values were median: 282; interquartile range (IQR): 132-598 µmol/24 h and median: 231; IQR: 175-306 µmol/24 h, respectively. Urinary 1-methylhistidine was associated with white meat intake [standardized β (st β): 0.20; 95% CI: 0.12, 0.28; P < 0.001], whereas urinary 3-methylhistidine was associated with red meat intake (st β: 0.30; 95% CI: 0.23, 0.38; P < 0.001). During median follow-up for 5.4 (IQR: 4.9-6.1) y, 145 (21%) died and 83 (12%) developed graft failure. Urinary 3-methylhistidine was inversely associated with mortality independently of potential confounders (HR per doubling: 0.55; 95% CI: 0.42, 0.72; P < 0.001). Both urinary 1-methylhistidine and urinary 3-methylhistidine were inversely associated with graft failure independent of potential confounders (HR per doubling: 0.84; 95% CI: 0.73, 0.96; P = 0.01; and 0.59; 95% CI: 0.41, 0.85; P = 0.004, respectively).
High urinary 3-methylhistidine, reflecting higher red meat intake, is independently associated with lower risk of mortality. High urinary concentrations of both 1- and 3-methylhistidine, of which the former reflects higher white meat intake, are independently associated with lower risk of graft failure in KTR. Future intervention studies are warranted to study the effect of high meat intake on mortality and graft failure in KTR, using these biomarkers.
目前尚不清楚摄入肉类是否有益于长期接受肾移植的患者和移植物的存活。
我们首先研究了先前描述的肉摄入量生物标志物 1-甲基组氨酸和 3-甲基组氨酸与从经过验证的食物频率问卷(FFQ)估计的白肉和红肉摄入量之间的关联。其次,我们研究了肉类摄入量生物标志物与肾移植受者长期结局的关系。
我们通过经过验证的检测方法测量了 678 名临床稳定的肾移植受者的 24 小时尿 1-甲基组氨酸和 3-甲基组氨酸的排泄量。通过线性回归评估横断面关联。我们使用 Cox 回归分析前瞻性研究了 log2 转换的生物标志物与死亡率和移植物衰竭的关系。
尿 1-甲基组氨酸和 3-甲基组氨酸的排泄值中位数分别为:282;四分位距(IQR):132-598 μmol/24 h 和中位数:231;IQR:175-306 μmol/24 h。尿 1-甲基组氨酸与白肉摄入量有关[标准化β(st β):0.20;95%置信区间(CI):0.12,0.28;P <0.001],而尿 3-甲基组氨酸与红肉类摄入量有关(st β:0.30;95%CI:0.23,0.38;P <0.001)。在中位随访 5.4(IQR:4.9-6.1)y 期间,有 145 人(21%)死亡,83 人(12%)发生移植物衰竭。尿 3-甲基组氨酸与死亡率独立于潜在混杂因素呈负相关(每翻倍 HR:0.55;95%CI:0.42,0.72;P <0.001)。尿 1-甲基组氨酸和尿 3-甲基组氨酸均与移植物衰竭独立相关,独立于潜在混杂因素(每翻倍 HR:0.84;95%CI:0.73,0.96;P = 0.01;和 0.59;95%CI:0.41,0.85;P = 0.004,分别)。
高尿 3-甲基组氨酸,反映较高的红肉类摄入量,与较低的死亡率风险独立相关。较高的 1-甲基组氨酸和 3-甲基组氨酸尿浓度均与肾移植受者的移植物衰竭风险较低独立相关,其中前者反映了较高的白肉摄入量。未来的干预研究需要使用这些生物标志物来研究高肉类摄入量对肾移植受者死亡率和移植物衰竭的影响。