The Second Affiliated Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China.
Sir Run Run Shaw Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China.
Nutrients. 2024 Jun 21;16(13):1978. doi: 10.3390/nu16131978.
With rapid increases in incidence, diverse subtypes, and complicated etiologies, kidney disease remains a global public health problem. Iron, as an essential trace element, has pleiotropic effects on renal function and the progression of kidney diseases. A two-sample Mendelian randomization (MR) analysis was implemented to determine the potential causal effects between systemic iron status on different kidney diseases. Systemic iron status was represented by four iron-related biomarkers: serum iron, ferritin, transferrin saturation (TfSat), and total iron binding capacity (TIBC). For systemic iron status, 163,511, 246,139, 131,471, and 135,430 individuals were included in the genome-wide association study (GWAS) of serum iron, ferritin, TfSat, and TIBC, respectively. For kidney diseases, 653,143 individuals (15,658 cases and 637,485 controls), 657,076 individuals (8160 cases and 648,916 controls), and 659,320 individuals (10,404 cases and 648,916 controls) were included for immunoglobulin A nephropathy (IgAN), acute kidney disease (AKD), and chronic kidney disease (CKD), respectively. Our MR results showed that increased serum iron [odds ratio (OR): 1.10; 95% confidence interval (95% CI): 1.04, 1.16; < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; < 0.0042) were associated with elevated IgAN risk. However, no significant associations were found between systemic iron status and AKD or CKD. In our MR study, the genetic evidence supports elevated systemic iron status as a causal effect on IgAN, which suggests a potential protective effect of iron chelation on IgAN patients.
随着发病率的快速增长、亚型的多样化和病因的复杂化，肾脏疾病仍然是一个全球性的公共卫生问题。铁作为一种必需的微量元素，对肾功能和肾脏疾病的进展有多种影响。本研究采用双样本 Mendelian 随机化（MR）分析来确定系统性铁状态与不同肾脏疾病之间的潜在因果关系。系统性铁状态由四个铁相关生物标志物来表示：血清铁、铁蛋白、转铁蛋白饱和度（TfSat）和总铁结合能力（TIBC）。对于系统性铁状态，分别有 163511、246139、131471 和 135430 人纳入了血清铁、铁蛋白、TfSat 和 TIBC 的全基因组关联研究（GWAS）。对于肾脏疾病，分别有 653143 人（15658 例病例和 637485 例对照）、657076 人（8160 例病例和 648916 例对照）和 659320 人（10404 例病例和 648916 例对照）纳入了免疫球蛋白 A 肾病（IgAN）、急性肾损伤（AKD）和慢性肾脏病（CKD）的研究。本 MR 研究结果表明，血清铁升高[比值比（OR）：1.10；95%置信区间（95%CI）：1.04，1.16；<0.0042]、铁蛋白（OR：1.30；95%CI：1.14，1.48；<0.0042）和 TfSat（OR：1.07；95%CI：1.04，1.11；<0.0042）与升高的 IgAN 风险相关，而 TIBC 降低（OR：0.92；95%CI：0.88，0.97；<0.0042）与升高的 IgAN 风险相关。然而，系统性铁状态与 AKD 或 CKD 之间没有显著关联。在本 MR 研究中，遗传证据支持升高的系统性铁状态对 IgAN 有因果关系，这表明铁螯合可能对 IgAN 患者有潜在的保护作用。
