区分早年生活和成年体型对慢性肾脏病风险的影响：一项孟德尔随机化研究

Separating the Effects of Early-Life and Adult Body Size on Chronic Kidney Disease Risk: A Mendelian Randomization Study.

作者信息

Li Xunliang, Zhao Wenman, Pan Haifeng, Wang Deguang

机构信息

Department of Nephrology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.

出版信息

J Obes Metab Syndr. 2025 Jan 30;34(1):65-74. doi: 10.7570/jomes24018. Epub 2025 Jan 13.

DOI:10.7570/jomes24018

PMID:39800332

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11799605/

Abstract

BACKGROUND

Whether there is a causal relationship between childhood obesity and increased risk of chronic kidney disease (CKD) remains controversial. This study sought to explore how body size in childhood and adulthood independently affects CKD risk in later life using a Mendelian randomization (MR) approach.

METHODS

Univariate and multivariate MR was used to estimate total and independent effects of body size exposures. Genetic associations with early-life and adult body size were obtained from a genome-wide association study of 453,169 participants in the U.K. Biobank, and genetic associations with CKD were obtained from the CKDGen and FinnGen consortia.

RESULTS

A larger genetically predicted early-life body size was associated with an increased risk of CKD (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.14 to 1.41; =1.70E-05) and increased blood urea nitrogen (BUN) levels (β=0.010; 95% CI, 0.005 to 0.021; =0.001). However, the association between the impact of early-life body size on CKD (OR, 1.12; 95% CI, 0.95 to 1.31; =0.173) and BUN level (β=0.001; 95% CI, -0.010 to 0.012; =0.853) did not remain statistically significant after adjustment for adult body size. Larger genetically predicted adult body size was associated with an increased risk of CKD (OR, 1.37; 95% CI, 1.21 to 1.54; =4.60E-07), decreased estimated glomerular filtration rate (β=-0.011; 95% CI, -0.017 to -0.006; =5.79E-05), and increased BUN level (β=0.010; 95% CI, 0.002 to 0.019; =0.018).

CONCLUSION

Our research indicates that the significant correlation between early-life body size and CKD risk is likely due to maintaining a large body size into adulthood.

摘要

背景

儿童肥胖与慢性肾脏病（CKD）风险增加之间是否存在因果关系仍存在争议。本研究旨在采用孟德尔随机化（MR）方法探讨儿童期和成年期的体型如何独立影响晚年的CKD风险。

方法

采用单变量和多变量MR来估计体型暴露的总体和独立效应。与儿童期和成年期体型的基因关联来自英国生物银行中453169名参与者的全基因组关联研究，与CKD的基因关联来自CKDGen和FinnGen联盟。

结果

遗传预测的儿童期体型较大与CKD风险增加相关（比值比[OR]，1.27；95%置信区间[CI]，1.14至1.41；P = 1.70E - 05），且血尿素氮（BUN）水平升高（β = 0.010；95% CI，0.005至0.021；P = 0.001）。然而，在调整成年期体型后，儿童期体型对CKD的影响（OR，1.12；95% CI，0.95至1.31；P = 0.173）和BUN水平（β = 0.001；95% CI，-0.010至0.012；P = 0.853）之间的关联不再具有统计学意义。遗传预测的成年期体型较大与CKD风险增加相关（OR，1.37；95% CI，1.21至1.54；P = 4.60E - 07），估计肾小球滤过率降低（β = -0.011；95% CI，-0.017至-0.006；P = 5.79E - 05），且BUN水平升高（β = 0.010；95% CI，0.002至0.019；P = 0.018）。