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Mendelian Randomization Analysis of Systemic Iron Status and Risk of Different Types of Kidney Disease

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Journal Nutrients
Date 2024 Jul 13
PMID 38999730
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Abstract

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.

References
1.
Chen J, Li X, Ge C, Min J, Wang F . The multifaceted role of ferroptosis in liver disease. Cell Death Differ. 2022; 29(3):467-480. PMC: 8901678. DOI: 10.1038/s41418-022-00941-0. View

2.
Romagnani P, Remuzzi G, Glassock R, Levin A, Jager K, Tonelli M . Chronic kidney disease. Nat Rev Dis Primers. 2017; 3:17088. DOI: 10.1038/nrdp.2017.88. View

3.
Schatzkin A, Abnet C, Cross A, Gunter M, Pfeiffer R, Gail M . Mendelian randomization: how it can--and cannot--help confirm causal relations between nutrition and cancer. Cancer Prev Res (Phila). 2009; 2(2):104-13. PMC: 3052774. DOI: 10.1158/1940-6207.CAPR-08-0070. View

4.
Kassebaum N . The Global Burden of Anemia. Hematol Oncol Clin North Am. 2016; 30(2):247-308. DOI: 10.1016/j.hoc.2015.11.002. View

5.
van Swelm R, Wetzels J, Swinkels D . The multifaceted role of iron in renal health and disease. Nat Rev Nephrol. 2019; 16(2):77-98. DOI: 10.1038/s41581-019-0197-5. View