{"title":"Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study.","authors":"Shisheng Han, Guangliang Xie, Yi Wang","doi":"10.1007/s10157-024-02623-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.</p><p><strong>Methods: </strong>The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies. Weighted generalized multivariate linear regression was employed to estimate the association between estradiol and eGFR and ACR, and a restricted cubic spline analysis was utilized to investigate potential nonlinear relationships.</p><p><strong>Results: </strong>A total of 8932 participants were included. Serum estradiol concentration was positively associated with eGFR after adjusting for potential covariates (β, 0.76; 95% CI 0.24 to 1.27) and with ACR (β, 5.99; 95% CI 1.62 to 10.36). A nonlinear positive association was found between estradiol and eGFR, while an inverse \"V\"-shaped relationship was seen with ACR. Sensitivity analyses confirmed the stability of the relationship between estradiol and eGFR but indicated a less robust association with ACR. Stratified analysis showed that the association between estradiol and eGFR was particularly significant in populations with CKD and hypertension. All forward MR analyses demonstrated a positive causal relationship between estradiol and eGFR, but no causality was found between estradiol and ACR. No reverse causal association was observed.</p><p><strong>Conclusions: </strong>Serum estradiol concentration was causally associated with eGFR. Further longitudinal research is needed to validate these findings.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10157-024-02623-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Previous studies have suggested a potential role of estrogen in the pathophysiology of chronic kidney disease (CKD); however, the association and causality between estrogen and kidney function remain unclear.
Methods: The cross-sectional correlation between serum estradiol concentration and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR) was analyzed using data from the National Health and Nutrition Examination Survey 2013-2016. Causality was tested using mutual bidirectional Mendelian randomization (MR) approaches based on six large-scale GWAS studies. Weighted generalized multivariate linear regression was employed to estimate the association between estradiol and eGFR and ACR, and a restricted cubic spline analysis was utilized to investigate potential nonlinear relationships.
Results: A total of 8932 participants were included. Serum estradiol concentration was positively associated with eGFR after adjusting for potential covariates (β, 0.76; 95% CI 0.24 to 1.27) and with ACR (β, 5.99; 95% CI 1.62 to 10.36). A nonlinear positive association was found between estradiol and eGFR, while an inverse "V"-shaped relationship was seen with ACR. Sensitivity analyses confirmed the stability of the relationship between estradiol and eGFR but indicated a less robust association with ACR. Stratified analysis showed that the association between estradiol and eGFR was particularly significant in populations with CKD and hypertension. All forward MR analyses demonstrated a positive causal relationship between estradiol and eGFR, but no causality was found between estradiol and ACR. No reverse causal association was observed.
Conclusions: Serum estradiol concentration was causally associated with eGFR. Further longitudinal research is needed to validate these findings.
期刊介绍:
Clinical and Experimental Nephrology is a peer-reviewed monthly journal, officially published by the Japanese Society of Nephrology (JSN) to provide an international forum for the discussion of research and issues relating to the study of nephrology. Out of respect for the founders of the JSN, the title of this journal uses the term “nephrology,” a word created and brought into use with the establishment of the JSN (Japanese Journal of Nephrology, Vol. 2, No. 1, 1960). The journal publishes articles on all aspects of nephrology, including basic, experimental, and clinical research, so as to share the latest research findings and ideas not only with members of the JSN, but with all researchers who wish to contribute to a better understanding of recent advances in nephrology. The journal is unique in that it introduces to an international readership original reports from Japan and also the clinical standards discussed and agreed by JSN.