Jiang Zhaoyu, Chen Lin, Liu Aihui, Qi Jiaping, Wang Jing, Li Yixuan, Jiang Huan, Zhang Ju, Huang Shan, Mao Chengliang, Ying Zhenhua
Zhejiang Province People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, China.
Department of Rheumatology and Immunology of Zhejiang Provincial People's Hospital, Center for General Practice Medicine, Hangzhou, China.
Front Med (Lausanne). 2024 May 16;11:1360026. doi: 10.3389/fmed.2024.1360026. eCollection 2024.
The extra-articular lesions of rheumatoid arthritis (RA) are reported to involve multiple organs and systems throughout the body, including the heart, kidneys, liver, and lungs. This study assessed the potential causal relationship between RA and the risk of chronic kidney diseases (CKDs) using the Mendelian randomization (MR) analysis.
Independent genetic instruments related to RA and CKD or CKD subtypes at the genome-wide significant level were chosen from the publicly shared summary-level data of genome-wide association studies (GWAS). Then, we obtained some single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs), which are associated with RA in individuals of European origin, and had genome-wide statistical significance (p5 × 10). The inverse-variance weighted (IVW) method was the main analysis method in MR analysis. The other methods, such as weighted median, MR-Egger, simple mode, and weighted mode were used as supplementary sensitivity analyses. Furthermore, the levels of pleiotropy and heterogeneity were assessed using Cochran's Q test and leave-one-out analysis. Furthermore, the relevant datasets were obtained from the Open GWAS database.
Using the IVW method, the main method in MR analysis, the results showed that genetically determined RA was associated with higher risks of CKD [odds ratio (OR): 1.22, 95% confidence interval (CI) 1.13-1.31; < 0.001], glomerulonephritis (OR: 1.23, 95% CI 1.15-1.31; < 0.000), amyloidosis (OR = 1.43, 95% CI 1.10-1.88, < 0.001), and renal failure (OR = 1.18, 95% CI 1.00-1.38, < 0.001). Then, using multiple MR methods, it was confirmed that the associations persisted in sensitivity analyses, and no pleiotropy was detected.
The findings revealed a causal relationship between RA and CKD, including glomerulonephritis, amyloidosis, and renal failure. Therefore, RA patients should pay more attention to monitoring their kidney function, thus providing the opportunity for earlier intervention and lower the risk of progression to CKDs.
据报道，类风湿关节炎（RA）的关节外病变累及全身多个器官和系统，包括心脏、肾脏、肝脏和肺部。本研究采用孟德尔随机化（MR）分析评估RA与慢性肾脏病（CKD）风险之间的潜在因果关系。
从公开共享的全基因组关联研究（GWAS）汇总水平数据中选择在全基因组显著水平上与RA和CKD或CKD亚型相关的独立遗传工具。然后，我们获得了一些单核苷酸多态性（SNP）作为工具变量（IV），这些SNP在欧洲血统个体中与RA相关，且具有全基因组统计学意义（p<5×10⁻⁸）。逆方差加权（IVW）方法是MR分析中的主要分析方法。其他方法，如加权中位数、MR-Egger、简单模式和加权模式，用作补充敏感性分析。此外，使用 Cochr an's Q检验和留一法分析评估多效性和异质性水平。此外，相关数据集来自开放GWAS数据库。
使用MR分析的主要方法IVW方法，结果显示，遗传决定的RA与CKD风险较高相关[比值比（OR）：1.22，95%置信区间（CI）1.13-1.31；P<0.001]、肾小球肾炎（OR：1.23，95%CI 1.15-1.31；P<0.0001）、淀粉样变性（OR=1.43，95%CI 1.10-1.88，P<0.001）和肾衰竭（OR= 1.18，95%CI 1.00-1.38，P<0.001）。然后，使用多种MR方法，证实这些关联在敏感性分析中持续存在，且未检测到多效性。
研究结果揭示了RA与CKD之间的因果关系，包括肾小球肾炎、淀粉样变性和肾衰竭。因此，RA患者应更加注意监测其肾功能，从而为早期干预提供机会并降低进展为CKD的风险。
