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Genetically predicted vitamin D and risk of chronic kidney disease progression: a Mendelian randomization study

Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Chronic kidney disease (CKD) is a global health burden, with vitamin D deficiency being a prevalent and modifiable risk factor. Vitamin D is involved in calcium-phosphate homeostasis, immune regulation, and anti-inflammatory pathways. However, its causal role in CKD progression remains uncertain. Methods: This study employed Mendelian randomization (MR) using genome-wide association study data to assess the causal effects of genetically predicted 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] levels on CKD progression in a KNOW-CKD (Korean Cohort Study for Outcome in Patients With Chronic Kidney Disease) cohort. CKD progression was defined as the estimated glomerular filtration rate (eGFR) slope, calculated using a linear mixed model to represent the rate of kidney function decline. Six MR methods were applied to ensure robust causal inference. Results: Genetic variants associated with higher 25(OH)D levels were linked to a significantly slower decline in eGFR, suggesting a protective effect on kidney function. Inverse variance weighted (IVW) analysis showed a negative association between genetically predicted 25(OH)D levels and eGFR slope (β = -0.246, SE = 0.093, p = 8.54E-03). A similar association was observed for 1,25(OH)2D using the radial IVW method (β = -0.256, SE = 0.057, p = 8.84E-06), with consistent findings from IVW and weighted median methods (p = 5.50E-04 and p = 1.13E-02, respectively). Sensitivity analyses using MR-Egger and MR-PRESSO showed no evidence of directional pleiotropy. Conclusion: This study provides evidence for a protective role of vitamin D in CKD progression, emphasizing the importance of maintaining adequate vitamin D levels. These findings highlight the potential for vitamin D-targeted therapeutic strategies in CKD management.
DOI: 10.23876/j.krcp.25.054
Authors: Juyeon Lee, Sangjun Lee, Sungji Moon, Yaeni Kim, Soo Wan Kim, Yeong Hoon Kim, Miyeon Han, Kook-Hwan Oh, Sue K. Park
Institutions: Seoul National University, Inje University Busan Paik Hospital, The Catholic University of Korea Seoul St. Mary's Hospital, Catholic University of Korea, Chonnam National University, National Medical Center, Seoul National University Hospital
Language: English
Field: Medicine
Open Access status: diamond
Funders: Korea Disease Control and Prevention Agency, National Research Foundation, Seoul National University, National Research Foundation of Korea, Seoul National University Hospital, Ministry of Science and ICT, South Korea, National Institutes of Health
Awards: G1046728144, G1741354496, G1822664431, G2578835210, G2958720900, G3222318771, G3454011106, G361955624, G3868902281, G4117616695, G4162607002, G4595649667, G5052606370, G5427811063, G5535594931, G571060924, G6224830658, G6284148230, G6630984261, G6739851886, G6897681724, G7448779488, G745724443, G8746780184, G8832687460
OpenAlex ID: W4416729476
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