Frequency of adding salt is a stronger predictor of chronic kidney disease in individuals with genetic risk.

Q2 Computer Science
Manu Shivakumar, Yanggyun Kim, Sang-Hyuk Jung, Jakob Woerner, Dokyoon Kim
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引用次数: 0

Abstract

The incidence of chronic kidney disease (CKD) is increasing worldwide, but there is no specific treatment available. Therefore, understanding and controlling the risk factors for CKD are essential for preventing disease occurrence. Salt intake raises blood pressure by increasing fluid volume and contributes to the deterioration of kidney function by enhancing the renin-angiotensin system and sympathetic tone. Thus, a low-salt diet is important to reduce blood pressure and prevent kidney diseases. With recent advancements in genetic research, our understanding of the etiology and genetic background of CKD has deepened, enabling the identification of populations with a high genetic predisposition to CKD. It is thought that the impact of lifestyle or environmental factors on disease occurrence or prevention may vary based on genetic factors. This study aims to investigate whether frequency of adding salt has different effects depending on genetic risk for CKD. CKD polygenic risk scores (PRS) were generated using CKDGen Consortium GWAS (N= 765,348) summary statics. Then we applied the CKD PRS to UK Biobank subjects. A total of 331,318 European individuals aged 40-69 without CKD were enrolled in the study between 2006-2010. The average age at enrollment of the participants in this study was 56.69, and 46% were male. Over an average follow-up period of 8 years, 12,279 CKD cases were identified. The group that developed CKD had a higher percentage of individuals who added salt (46.37% vs. 43.04%) and higher CKD high-risk PRS values compared to the group that did not develop CKD (23.53% vs. 19.86%). We classified the individuals into four groups based on PRS: low (0-19%), intermediate (20-79%), high (80-94%), very high (≥ 95%). Incidence of CKD increased incrementally according to CKD PRS even after adjusting for age, sex, race, Townsend deprivation index, body mass index, estimated glomerular filtration rate, smoking, alcohol, physical activity, diabetes mellitus, dyslipidemia, hypertension, coronary artery diseases, cerebrovascular diseases at baseline. Compared to the "never/rarely" frequency of adding salt group, "always" frequency of adding salt group had an increasing incidence of CKD proportionate to the degree of frequency of adding salt. However, the significant association of "always" group on incident CKD disappeared in the low PRS group. This study validated the signal from PRSs for CKD across a large cohort and confirmed that frequency of adding salt contributes to the occurrence of CKD. Additionally, it confirmed that the effect of frequency of "always" adding salt on CKD incidence is greater in those with more than intermediate CKD-PRS. This study suggests that increased salt intake is particularly concerning for individuals with genetic risk factors for CKD, underscoring the clinical importance of reducing salt intake for these individuals.

在有遗传风险的个体中,加盐频率是慢性肾脏疾病的一个更强的预测因子。
慢性肾脏疾病(CKD)的发病率在全球范围内呈上升趋势,但目前尚无专门的治疗方法。因此,了解和控制CKD的危险因素对预防疾病的发生至关重要。盐的摄入通过增加体液量而升高血压,并通过增强肾素-血管紧张素系统和交感神经张力而导致肾功能恶化。因此,低盐饮食对降低血压和预防肾脏疾病很重要。随着最近遗传学研究的进展,我们对CKD的病因学和遗传背景的理解已经加深,从而能够识别出CKD高遗传易感性人群。人们认为,生活方式或环境因素对疾病发生或预防的影响可能因遗传因素而异。本研究旨在探讨食盐添加频率是否对CKD遗传风险有不同的影响。使用CKDGen Consortium GWAS (N= 765,348)汇总统计生成CKD多基因风险评分(PRS)。然后我们将CKD PRS应用于UK Biobank受试者。2006-2010年间,共有331,318名年龄在40-69岁之间、无CKD的欧洲人参加了这项研究。本研究参与者入组时的平均年龄为56.69岁,其中46%为男性。在平均8年的随访期间,确定了12,279例CKD病例。与未发生CKD的组相比,发生CKD的组添加盐的个体比例更高(46.37%对43.04%),CKD高危PRS值也更高(23.53%对19.86%)。我们根据PRS将个体分为4组:低(0-19%)、中(20-79%)、高(80-94%)、极高(≥95%)。即使在调整了年龄、性别、种族、Townsend剥夺指数、体重指数、肾小球滤过率、吸烟、饮酒、体力活动、糖尿病、血脂异常、高血压、冠状动脉疾病、脑血管疾病等基线因素后,根据CKD PRS, CKD的发病率仍呈递增趋势。与“从不/很少”加盐频率组相比,“经常”加盐频率组CKD发病率与加盐频率成正比。然而,低PRS组“总是”组与CKD事件的显著相关性消失。本研究在一个大型队列中验证了PRSs对CKD的信号,并证实了添加盐的频率有助于CKD的发生。此外,它证实了“总是”加盐频率对CKD发病率的影响在中度以上的CKD- prs患者中更大。这项研究表明,增加盐摄入量对具有CKD遗传风险因素的个体尤其重要,强调了减少这些个体盐摄入量的临床重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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CiteScore
4.50
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