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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Renal Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1348854
This article is part of the Research Topic Emerging Talents in Renal Endocrinology: 2023 View all 10 articles

Cause effects of serum calcium, phosphate, and 25-hydroxyvitamin D on kidney function: A Genetic Correlation, Pleiotropic Analysis, and Mendelian Randomization study

Provisionally accepted
Yanjun Liang Yanjun Liang 1Shuang Liang Shuang Liang 1Dayang Xie Dayang Xie 1Xinru Guo Xinru Guo 1Chen Yang Chen Yang 2Tuo Xiao Tuo Xiao 1Kaiting Zhuang Kaiting Zhuang 1Yongxing Xu Yongxing Xu 1Yong Wang Yong Wang 1Bin Wang Bin Wang 1zhou zhang zhou zhang 1Xiangmei Chen Xiangmei Chen 1Yizhi Chen Yizhi Chen 1GUANGYAN CAI GUANGYAN CAI 1*
  • 1 People's Liberation Army General Hospital, Beijing, China
  • 2 Nankai University, Tianjin, China

The final, formatted version of the article will be published soon.

    Background: Existing studies investigating the impact of serum calcium (Ca), phosphate (P), 25 hydroxyvitamin D (25[OH]D), and parathyroid hormone (PTH) levels on kidney function have produced inconsistent results. Further research is needed to establish the direct causal relationship between these factors and kidney function.The study used Genome-wide association study datasets for exposure and outcome, mainly derived from the UK Biobank and CKDGen Consortium, with sample sizes ranging from 3,310 to 480,699 individuals of European ancestry. Heritability and genetic correlations among these phenotypes were assessed using linkage disequilibrium score regression (LDSC) and phenotypes with a heritability z-score < 4 were excluded from further analyses. Pleiotropic analyses were performed to identify potential horizontal pleiotropic variants at gene and LD-independent locus levels. Mendelian randomization (MR) analysis, using instrumental variables (IVs) based on two distinct selection criteria, was conducted to investigate the potential causal relationships between serum Ca, P, 25(OH)D, PTH, and kidney function.Results: PTH was excluded from further analysis due to a heritability z-score < 4. Genetic correlations were observed between serum Ca and urine albumin-to-creatinine ratio (UACR) (rg 0.202, P-value 5.0E-04), serum 25(OH)D and estimated glomerular filtration rate using serum creatinine (eGFRcrea) (rg -0.094; P-value 1.4E-05), as well as serum 25(OH)D and blood urea nitrogen (BUN) (rg 0.127; Pvalue 1.7E-06). In Univariable MR analysis using IVs based on two different selection criteria, it consistently demonstrated that genetically predicted serum Ca consistently showed an increase in UACR (beta 0.11, P-value 2.0E-03; beta 0.13, P-value 2.0E-04). Similarly, serum P was associated with a decrease in eGFRcrea (beta -0.01, P-value 2.0E-04; beta -0.005, P-value 2.0E-03) and an increase in BUN (beta 0.02, P-value 3.0E-03; beta 0.02, P-value 7.5E-07). The influence of serum P on kidney function was further supported in Multivariable MR analysis. However, genetically predicted 25(OH)D did not have a significant impact on kidney function.Conclusions: Elevated serum Ca or P levels could both impair kidney function, while 25(OH)D has no impact on renal function.

    Keywords: Calcium, Phosphate, 25-hydroxyvitamin D, Parathyroid Hormone, Kidney function, Mendelian randomization, genetic correlation, pleiotropic analysis

    Received: 03 Dec 2023; Accepted: 03 Sep 2024.

    Copyright: © 2024 Liang, Liang, Xie, Guo, Yang, Xiao, Zhuang, Xu, Wang, Wang, zhang, Chen, Chen and CAI. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: GUANGYAN CAI, People's Liberation Army General Hospital, Beijing, China

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