Abstract：
BACKGROUND: Rapid kidney function decline (RKFD) is a main clinical feature of early chronic kidney disease (CKD) in type 2 diabetes (T2D). Environmental and genetic factors influencing RKFD remain inadequately elucidated.
OBJECTIVE: This study aimed to examine the associations of metals with RKFD among T2D and to further investigate the effect of metal mixtures on RKFD with the modifying effect of genetic susceptibility.
METHODS: This study included 2209 people with T2D (1942 had genotyping data) free of CKD at baseline from the Dongfeng Tongji cohort. We used inductively coupled plasma-mass spectrometry (ICP-MS) to measure 23 metals in baseline plasma. Using elastic net (ENET), multivariate logistic regression, and Bayesian kernel machine regression (BKMR) model, we examined independent associations of multiple metals with RKFD. We calculated the environmental risk score (ERS) to assess the effects of metal mixtures on RKFD and the genetic risk score (GRS) to assess genetic susceptibility. RKFD was defined as estimated glomerular filtration rate (eGFR) loss >3 ml/min/1.73 m2/year.
RESULTS: During a median of 9.8 years follow-up, 262 participants developed RKFD. Aluminum, vanadium, zinc, selenium, rubidium, tin, barium, and tungsten were screened from ENET. In multivariate logistic models, vanadium, selenium, and tungsten were negatively associated with RKFD, while zinc, tin, and rubidium were positively associated. The BKMR showed a nonlinear association of vanadium and rubidium with RKFD and interactions between metals (barium‑vanadium, barium‑rubidium). The ERS was positive associated with RKFD (per SD increase in ERS, OR = 1.94, 95 % CI: 1.66, 2.27). No significant interaction between ERS and GRS was observed on RKFD, however, participants in the highest ERS and GRS group had the highest RKFD risk.
CONCLUSIONS: Vanadium and rubidium were associated with RKFD in T2D. Metal mixtures was associated with an increased risk of RKFD in T2D, particularly in those at high genetic risk.
OBJECTIVE: This study aimed to examine the associations of metals with RKFD among T2D and to further investigate the effect of metal mixtures on RKFD with the modifying effect of genetic susceptibility.
METHODS: This study included 2209 people with T2D (1942 had genotyping data) free of CKD at baseline from the Dongfeng Tongji cohort. We used inductively coupled plasma-mass spectrometry (ICP-MS) to measure 23 metals in baseline plasma. Using elastic net (ENET), multivariate logistic regression, and Bayesian kernel machine regression (BKMR) model, we examined independent associations of multiple metals with RKFD. We calculated the environmental risk score (ERS) to assess the effects of metal mixtures on RKFD and the genetic risk score (GRS) to assess genetic susceptibility. RKFD was defined as estimated glomerular filtration rate (eGFR) loss >3 ml/min/1.73 m2/year.
RESULTS: During a median of 9.8 years follow-up, 262 participants developed RKFD. Aluminum, vanadium, zinc, selenium, rubidium, tin, barium, and tungsten were screened from ENET. In multivariate logistic models, vanadium, selenium, and tungsten were negatively associated with RKFD, while zinc, tin, and rubidium were positively associated. The BKMR showed a nonlinear association of vanadium and rubidium with RKFD and interactions between metals (barium‑vanadium, barium‑rubidium). The ERS was positive associated with RKFD (per SD increase in ERS, OR = 1.94, 95 % CI: 1.66, 2.27). No significant interaction between ERS and GRS was observed on RKFD, however, participants in the highest ERS and GRS group had the highest RKFD risk.
CONCLUSIONS: Vanadium and rubidium were associated with RKFD in T2D. Metal mixtures was associated with an increased risk of RKFD in T2D, particularly in those at high genetic risk.
摘要：
背景：快速肾功能下降（RKFD）是2型糖尿病（T2D）早期慢性肾脏病（CKD）的主要临床特征。影响RKFD的环境和遗传因素仍未得到充分阐明。
目的：本研究旨在研究T2D中金属与RKFD的关系，并进一步研究金属混合物对RKFD的影响以及遗传易感性的改变作用。
方法：本研究纳入了从东风同济队列中基线无CKD的2209名T2D患者（1942年有基因分型数据）。我们使用电感耦合等离子体质谱法(ICP-MS)测量基线等离子体中的23种金属。使用弹性网(ENET)，多元逻辑回归，和贝叶斯核机回归(BKMR)模型，我们检查了多种金属与RKFD的独立关联。我们计算了环境风险评分（ERS）以评估金属混合物对RKFD的影响，并计算了遗传风险评分（GRS）以评估遗传易感性。RKFD定义为估计的肾小球滤过率(eGFR)损失>3ml/min/1.73m2/年。
结果：在中位9.8年的随访中，262名参与者开发了RKFD。铝，钒，锌，硒,铷,锡，钡,从ENET中筛选出钨。在多变量逻辑模型中，钒，硒,钨与RKFD呈负相关，而锌，锡，与铷呈正相关。BKMR显示出钒和铷与RKFD的非线性关联以及金属之间的相互作用（钡-钒，钡-铷）。ERS与RKFD呈正相关(ERS的每SD增加，OR=1.94，95%CI：1.66，2.27）。在RKFD上没有观察到ERS和GRS之间的显著相互作用，然而,ERS和GRS组的参与者RKFD风险最高.
结论：钒和铷与T2D的RKFD相关。金属混合物与T2D中RKFD的风险增加有关，特别是那些遗传风险高的人。
目的：本研究旨在研究T2D中金属与RKFD的关系，并进一步研究金属混合物对RKFD的影响以及遗传易感性的改变作用。
方法：本研究纳入了从东风同济队列中基线无CKD的2209名T2D患者（1942年有基因分型数据）。我们使用电感耦合等离子体质谱法(ICP-MS)测量基线等离子体中的23种金属。使用弹性网(ENET)，多元逻辑回归，和贝叶斯核机回归(BKMR)模型，我们检查了多种金属与RKFD的独立关联。我们计算了环境风险评分（ERS）以评估金属混合物对RKFD的影响，并计算了遗传风险评分（GRS）以评估遗传易感性。RKFD定义为估计的肾小球滤过率(eGFR)损失>3ml/min/1.73m2/年。
结果：在中位9.8年的随访中，262名参与者开发了RKFD。铝，钒，锌，硒,铷,锡，钡,从ENET中筛选出钨。在多变量逻辑模型中，钒，硒,钨与RKFD呈负相关，而锌，锡，与铷呈正相关。BKMR显示出钒和铷与RKFD的非线性关联以及金属之间的相互作用（钡-钒，钡-铷）。ERS与RKFD呈正相关(ERS的每SD增加，OR=1.94，95%CI：1.66，2.27）。在RKFD上没有观察到ERS和GRS之间的显著相互作用，然而,ERS和GRS组的参与者RKFD风险最高.
结论：钒和铷与T2D的RKFD相关。金属混合物与T2D中RKFD的风险增加有关，特别是那些遗传风险高的人。
