Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, Korea.
Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University, Seoul, Korea.
Endocrinol Metab (Seoul). 2021 Dec;36(6):1298-1306. doi: 10.3803/EnM.2021.1226. Epub 2021 Nov 26.
Mitochondrial dysfunction is strongly associated with several kidney diseases. However, no studies have evaluated the potential renal hazards of serum mitochondria-inhibiting substance (MIS) and aryl hydrocarbon receptor ligand (AhRL) levels.
We used serum level of MIS and AhRL and clinical renal outcomes from 1,511 participants of a prospective community-based cohort in Ansung. MIS was evaluated based on intracellular adenosine triphosphate (MIS-ATP) or reactive oxygen species (MIS-ROS) generation measured using cell-based assays.
During a mean 6.9-year follow-up, 84 participants (5.6%) developed a rapid decline in kidney function. In the lowest quartile group of MIS-ATP, patients were older and had metabolically deleterious parameters. In multivariate logistic regression analysis, higher MIS-ATP was associated with decreased odds for rapid decline: the odds ratio (OR) of 1% increase was 0.977 (95% confidence interval [CI], 0.957 to 0.998; P=0.031), while higher MIS-ROS was marginally associated with increased odds for rapid decline (OR, 1.014; 95% CI, 0.999 to 1.028; P=0.055). However, serum AhRL was not associated with the rapid decline in kidney function. In subgroup analysis, the renal hazard of MIS was particularly evident in people with hypertension and low baseline kidney function.
Serum MIS was independently associated with a rapid decline in kidney function, while serum AhRL was not. The clinical implication of renal hazard on serum MIS requires further evaluation in future studies.
线粒体功能障碍与多种肾脏疾病密切相关。然而，目前尚无研究评估血清线粒体抑制物质（MIS）和芳烃受体配体（AhRL）水平对肾脏的潜在危害。
我们使用了前瞻性社区队列研究中 1511 名参与者的血清 MIS 和 AhRL 水平及临床肾脏结局数据。通过细胞测定法检测细胞内三磷酸腺苷（MIS-ATP）或活性氧（MIS-ROS）的产生来评估 MIS。
在平均 6.9 年的随访期间，84 名参与者（5.6%）的肾功能迅速下降。在 MIS-ATP 最低四分位组中，患者年龄较大且存在代谢有害参数。在多变量逻辑回归分析中，较高的 MIS-ATP 与快速下降的几率降低相关：1%的增加比值比（OR）为 0.977（95%置信区间 [CI]，0.957 至 0.998；P=0.031），而较高的 MIS-ROS 与快速下降的几率增加呈边缘相关（OR，1.014；95%CI，0.999 至 1.028；P=0.055）。然而，血清 AhRL 与肾功能的快速下降无关。在亚组分析中，MIS 的肾脏危害在高血压和基线肾功能较低的人群中尤为明显。
血清 MIS 与肾功能的快速下降独立相关，而血清 AhRL 则没有。在未来的研究中，需要进一步评估血清 MIS 的肾脏危害的临床意义。
