随着发病率的迅速增加,不同的亚型,和复杂的病因,肾脏疾病仍然是一个全球性的公共卫生问题。熨斗,作为一种必需的微量元素,对肾功能和肾脏疾病的进展具有多效性作用。实施双样本孟德尔随机化(MR)分析以确定全身铁状态对不同肾脏疾病之间的潜在因果关系。全身铁状态由四种与铁相关的生物标志物代表:血清铁,铁蛋白,转铁蛋白饱和度(TfSat),和总铁结合能力(TIBC)。对于全身铁状态,163,511,246,139,131,471和135,430个人被纳入血清铁的全基因组关联研究(GWAS),铁蛋白,TfSat,和TIBC,分别。对于肾脏疾病,653,143人(15,658例病例和637,485例对照),657,076人(8160例病例和648,916例对照),并纳入659,320例(10,404例和648,916例对照)的免疫球蛋白A肾病(IgAN),急性肾病(AKD),和慢性肾病(CKD),分别。我们的MR结果显示血清铁增加[优势比(OR):1.10;95%置信区间(95%CI):1.04,1.16;p<0.0042],铁蛋白(OR:1.30;95%CI:1.14,1.48;p<0.0042),和TfSat(OR:1.07;95%CI:1.04,1.11;p<0.0042)]和降低的TIBC(OR:0.92;95%CI:0.88,0.97;p<0.0042)与IgAN风险升高相关。然而,未发现全身铁状态与AKD或CKD之间存在显著关联.在我们的MR研究中,遗传证据支持全身铁状态升高是IgAN的因果效应,这表明铁螯合对IgAN患者具有潜在的保护作用。
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; p < 0.0042], ferritin (OR: 1.30; 95% CI: 1.14, 1.48; p < 0.0042), and TfSat (OR: 1.07; 95% CI: 1.04, 1.11; p < 0.0042)] and decreased TIBC (OR: 0.92; 95% CI: 0.88, 0.97; p < 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.