Jing Liu1, Hui Zhang1, Zheng Dong1, Jingru Zhou2, Yanyun Ma2, Yuan Li1, Qiaoxia Qian2, Ziyu Yuan3, Juan Zhang3, Yajun Yang1,3, Xiaofeng Wang1,3, Xingdong Chen1,3, Hejian Zou4,5, Li Jin1,3, Jiucun Wang6,7,8. 1. State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005, Songhu Road, Shanghai, China. 2. Ministry of Education (MOE) Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China. 3. Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China. 4. Division of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China. 5. Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China. 6. State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, 2005, Songhu Road, Shanghai, China. jcwang@fudan.edu.cn. 7. Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu Province, China. jcwang@fudan.edu.cn. 8. Institute of Rheumatology, Immunology and Allergy, Fudan University, Shanghai, China. jcwang@fudan.edu.cn.
Abstract
PURPOSE: High levels of serum uric acid can predict the progression of stage I and II chronic kidney disease (CKD), but whether serum urate is an independent risk factor or has causal impact on serum creatinine (SCr) and renal function remains unclear. METHODS: Mendelian randomization was used to determine whether serum uric acid had a causal effect on renal function, represented by estimated glomerular filtration rate (eGFR), with potential confounding factors, in 3734 subjects from the Taizhou Longitudinal Study. In the two-stage least squares method of Mendelian randomization, serum uric acid level was selected as the exposure, genetic risk score of uric acid transporters was selected as the instrumental variable, and SCr and eGFR were selected as the outcomes. RESULTS: The result of the analysis showed that increased serum uric acid was not a causal effect on renal function, but it was a causal effect on reducing estimated glomerular filtration rate in both the female population and the subjects who were under 65 years old. We also found that increased serum uric acid levels led to impaired renal function only in the subjects with normal eGFR values. In addition, the serum uric acid was a risk factor for renal function in the subjects with relatively high levels of fasting glucose or who were currently smokers. CONCLUSIONS: Although serum urate is not an independent risk factor for renal dysfunction, it has a causal effect on renal dysfunction in either female or individuals of under 65, or normal eGFR, or high level of fasting glucose, or current smokers.
PURPOSE: High levels of serum uric acid can predict the progression of stage I and II chronic kidney disease (CKD), but whether serum urate is an independent risk factor or has causal impact on serum creatinine (SCr) and renal function remains unclear. METHODS: Mendelian randomization was used to determine whether serum uric acid had a causal effect on renal function, represented by estimated glomerular filtration rate (eGFR), with potential confounding factors, in 3734 subjects from the Taizhou Longitudinal Study. In the two-stage least squares method of Mendelian randomization, serum uric acid level was selected as the exposure, genetic risk score of uric acid transporters was selected as the instrumental variable, and SCr and eGFR were selected as the outcomes. RESULTS: The result of the analysis showed that increased serum uric acid was not a causal effect on renal function, but it was a causal effect on reducing estimated glomerular filtration rate in both the female population and the subjects who were under 65 years old. We also found that increased serum uric acid levels led to impaired renal function only in the subjects with normal eGFR values. In addition, the serum uric acid was a risk factor for renal function in the subjects with relatively high levels of fasting glucose or who were currently smokers. CONCLUSIONS: Although serum urate is not an independent risk factor for renal dysfunction, it has a causal effect on renal dysfunction in either female or individuals of under 65, or normal eGFR, or high level of fasting glucose, or current smokers.
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