尿 3-羟基异戊酰肉碱排泄、蛋白质能量营养不良与肾移植受者全因死亡率的关系：来自 TransplantLines 队列研究的结果。

Urinary 3-hydroxyisovaleryl carnitine excretion, protein energy malnutrition and risk of all-cause mortality in kidney transplant recipients: Results from the TransplantLines cohort studies.

机构信息

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, 9713 GZ, Groningen, the Netherlands.

Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

出版信息

Clin Nutr. 2021 Apr;40(4):2109-2120. doi: 10.1016/j.clnu.2020.09.035. Epub 2020 Oct 1.

DOI:10.1016/j.clnu.2020.09.035

PMID:33071013

Abstract

BACKGROUND

Leucine is an essential amino acid and a potent stimulator of muscle protein synthesis. Since muscle wasting is a major risk factor for mortality in kidney transplant recipients (KTR), dietary leucine intake might be linked to long-term mortality. Urinary 3-hydroxyisovaleryl carnitine (3-HIC) excretion, a functional marker of marginal biotin deficiency, may also serve as a marker for dietary leucine intake.

OBJECTIVE

In this study we aimed to investigate the cross-sectional determinants of urinary 3-HIC excretion and to prospectively investigate the association of urinary 3-HIC excretion with all-cause mortality in KTR.

DESIGN

Urinary 3-HIC excretion and plasma biotin were measured in a longitudinal cohort of 694 stable KTR. Cross-sectional and prospective analyses were performed using ordinary least squares linear regression analyses and Cox regression analyses, respectively.

RESULTS

In KTR (57% male, 53 ± 13 years, estimated glomerular filtration rate 45 ± 19 mL/min/1.73 m), urinary 3-HIC excretion (0.80 [0.57-1.16] μmol/24 h) was significantly associated with plasma biotin (std. β = -0.17; P < 0.001). Subsequent adjustment for potential covariates revealed urinary creatinine excretion (std. β = 0.24; P < 0.001) and urinary urea excretion (std. β = 0.53; P < 0.001) as the primary determinant of urinary 3-HIC excretion. Whereas plasma biotin explained only 1% of the variance in urinary 3-HIC excretion, urinary urea excretion explained >45%. During median follow-up for 5.4 [4.8-6.1] years, 150 (22%) patients died. Log-transformed urinary 3-HIC excretion was inversely associated with all-cause mortality (HR: 0.52 [0.43-0.63]; P < 0.001). This association was independent of potential confounders.

CONCLUSIONS

Urinary 3-HIC excretion more strongly serves as a marker of leucine intake than of biotin status. A higher urinary 3-HIC excretion is associated with a lower risk of all-cause mortality. Future studies are warranted to explore the underlying mechanism.

TRIAL REGISTRATION ID

NCT02811835. TRIAL REGISTRATION URL: https://clinicaltrials.gov/ct2/show/NCT02811835.

摘要

背景

亮氨酸是一种必需氨基酸，也是肌肉蛋白质合成的有效刺激物。由于肌肉消耗是肾移植受者（KTR）死亡的主要危险因素，因此膳食亮氨酸的摄入量可能与长期死亡率有关。尿 3-羟基异戊酰肉碱（3-HIC）排泄，边缘生物素缺乏的功能性标志物，也可以作为膳食亮氨酸摄入量的标志物。

目的

本研究旨在探讨尿 3-HIC 排泄的横断面决定因素，并前瞻性研究尿 3-HIC 排泄与 KTR 全因死亡率的关系。

设计

在一个 694 例稳定 KTR 的纵向队列中测量尿 3-HIC 排泄和血浆生物素。使用普通最小二乘线性回归分析和 Cox 回归分析分别进行横断面和前瞻性分析。

结果

在 KTR（57%男性，53±13 岁，估计肾小球滤过率 45±19 mL/min/1.73 m）中，尿 3-HIC 排泄（0.80[0.57-1.16]μmol/24 h）与血浆生物素显著相关（标准β=-0.17；P<0.001）。随后调整潜在的混杂因素后发现，尿肌酐排泄（标准β=0.24；P<0.001）和尿尿素排泄（标准β=0.53；P<0.001）是尿 3-HIC 排泄的主要决定因素。虽然血浆生物素仅解释了尿 3-HIC 排泄的 1%的变异，但尿尿素排泄解释了超过 45%的变异。在中位随访 5.4[4.8-6.1]年后，150（22%）名患者死亡。经对数转换的尿 3-HIC 排泄与全因死亡率呈负相关（HR：0.52[0.43-0.63]；P<0.001）。这种关联独立于潜在的混杂因素。