Yang Jiaqi, Bernard Lauren, Chen Jingsha, Sullivan Valerie K, Yu Bing, Rhee Eugene P, Welling Paul A, Rebholz Casey M
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.
Clin J Am Soc Nephrol. 2025 Sep 18. doi: 10.2215/CJN.0000000864.
There is a need for objective biomarkers of dietary potassium. The mechanisms through which dietary potassium influences kidney health are incompletely understood.
Atherosclerosis Risk in Communities study participants at visit 3 (1993-1995) with dietary and proteomics data were randomly divided into discovery (N=6,814) and replication (N=3,380) sets. We examined associations between dietary potassium and 4,955 aptamers using multivariable linear regression, adjusting for sociodemographic factors, health behaviors, and estimated glomerular filtration rate, with a false discovery rate of 0.05. Then, we tested the prospective associations between potassium-related proteins and incident chronic kidney disease (CKD).
Dietary potassium was significantly associated with 147 proteins in discovery, of which 85 (33 positive, 52 negative) replicated. Of 85 replicated proteins, 30 were selected by elastic net and improved prediction of high dietary potassium individually and collectively. Over a median follow-up of 21 years, 1,698 CKD cases developed. A score derived from 30 elastic net-selected dietary potassium-related proteins was associated with 7% lower risk of CKD (95% CI, 0.88-0.98, P=0.01). Of 85 potassium-related proteins from replication, 10 were associated with incident CKD. Specifically, pigment epithelium-derived factor and follistatin-related protein 3 were inversely associated with potassium and linked to 57% and 55% higher risk of CKD, respectively. Positively associated with potassium, TOM1-like protein 1 and serine/threonine-protein kinase pim-1 were associated with 28% and 26% lower risk of CKD, respectively. A score of 6 proteins mediated the association between potassium and CKD risk was associated with 13% lower risk of CKD (95% CI, 0.83-0.92, P=8.09×10-7).
Proteins associated with dietary potassium and incident CKD represented biological pathways including iron metabolism, mitochondrial function, fibrosis, and immune-inflammatory responses, which help explain the impact of potassium intake on CKD.
需要膳食钾的客观生物标志物。膳食钾影响肾脏健康的机制尚未完全了解。
社区动脉粥样硬化风险研究中第3次访视（1993 - 1995年）时具有膳食和蛋白质组学数据的参与者被随机分为发现组（N = 6814）和复制组（N = 3380）。我们使用多变量线性回归研究膳食钾与4955种适体之间的关联，并对社会人口统计学因素、健康行为和估计的肾小球滤过率进行调整，错误发现率为0.05。然后，我们测试了钾相关蛋白与新发慢性肾脏病（CKD）之间的前瞻性关联。
在发现组中，膳食钾与147种蛋白质显著相关，其中85种（33种为正相关，52种为负相关）得到复制。在85种复制的蛋白质中，30种通过弹性网络选择，分别单独和共同改善了对高膳食钾的预测。在中位随访21年期间，发生了1698例CKD病例。由30种弹性网络选择的膳食钾相关蛋白得出的评分与CKD风险降低7%相关（95%CI，0.88 - 0.98，P = 0.01）。在复制组的85种钾相关蛋白中，10种与新发CKD相关。具体而言，色素上皮衍生因子和卵泡抑素相关蛋白3与钾呈负相关，分别与CKD风险升高57%和55%相关。与钾呈正相关的TOM1样蛋白1和丝氨酸/苏氨酸蛋白激酶pim - 1分别与CKD风险降低28%和26%相关。由6种介导钾与CKD风险关联的蛋白质得出的评分与CKD风险降低13%相关（95%CI，0.83 - .92，P = 8.09×10 - 7）。
与膳食钾和新发CKD相关的蛋白质代表了包括铁代谢、线粒体功能、纤维化和免疫炎症反应在内的生物学途径，这有助于解释钾摄入对CKD的影响。
