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Published in: International Urology and Nephrology 11/2017

01-11-2017 | Nephrology - Original Paper

Mendelian randomization analysis indicates serum urate has a causal effect on renal function in Chinese women

Authors: Jing Liu, Hui Zhang, Zheng Dong, Jingru Zhou, Yanyun Ma, Yuan Li, Qiaoxia Qian, Ziyu Yuan, Juan Zhang, Yajun Yang, Xiaofeng Wang, Xingdong Chen, Hejian Zou, Li Jin, Jiucun Wang

Published in: International Urology and Nephrology | Issue 11/2017

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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.
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Literature
1.
go back to reference Pasalic D, Marinkovic N, Feher-Turkovic L (2012) Uric acid as one of the important factors in multifactorial disorders–facts and controversies. Biochemia medica 22:63–75CrossRefPubMedPubMedCentral Pasalic D, Marinkovic N, Feher-Turkovic L (2012) Uric acid as one of the important factors in multifactorial disorders–facts and controversies. Biochemia medica 22:63–75CrossRefPubMedPubMedCentral
8.
13.
go back to reference Kang DH et al (2002) A role for uric acid in the progression of renal disease. J Am Soc Nephrol 13:2888–2897CrossRefPubMed Kang DH et al (2002) A role for uric acid in the progression of renal disease. J Am Soc Nephrol 13:2888–2897CrossRefPubMed
19.
go back to reference McKeigue PM et al (2010) Bayesian methods for instrumental variable analysis with genetic instruments (‘Mendelian randomization’): example with urate transporter SLC2A9 as an instrumental variable for effect of urate levels on metabolic syndrome. Int J Epidemiol 39:907–918. doi:10.1093/ije/dyp397 CrossRefPubMedPubMedCentral McKeigue PM et al (2010) Bayesian methods for instrumental variable analysis with genetic instruments (‘Mendelian randomization’): example with urate transporter SLC2A9 as an instrumental variable for effect of urate levels on metabolic syndrome. Int J Epidemiol 39:907–918. doi:10.​1093/​ije/​dyp397 CrossRefPubMedPubMedCentral
25.
go back to reference Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27:1133–1163. doi:10.1002/sim.3034 CrossRefPubMed Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27:1133–1163. doi:10.​1002/​sim.​3034 CrossRefPubMed
28.
go back to reference Hausman JA (1978) Specification tests in econometrics. Econometrica 46(6):1251–1271CrossRef Hausman JA (1978) Specification tests in econometrics. Econometrica 46(6):1251–1271CrossRef
29.
go back to reference Eleftheriadis T et al (2017) Uric acid increases cellular and humoral alloimmunity in primary human peripheral blood mononuclear cells. Nephrology. doi:10.1111/nep.13069 PubMed Eleftheriadis T et al (2017) Uric acid increases cellular and humoral alloimmunity in primary human peripheral blood mononuclear cells. Nephrology. doi:10.​1111/​nep.​13069 PubMed
33.
go back to reference Tremblay AM, Dufour CR, Ghahremani M, Reudelhuber TL, Giguere V (2010) Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway. Mol Endocrinol 24:22–32 (10.1210/me.2009-0254) CrossRefPubMedPubMedCentral Tremblay AM, Dufour CR, Ghahremani M, Reudelhuber TL, Giguere V (2010) Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway. Mol Endocrinol 24:22–32 (10.1210/me.2009-0254) CrossRefPubMedPubMedCentral
35.
go back to reference Nacak H et al (2015) Uric acid is not associated with decline in renal function or time to renal replacement therapy initiation in a referred cohort of patients with Stage III, IV and V chronic kidney disease. Nephrol Dial Transplant 30:2039–2045. doi:10.1093/ndt/gfv225 CrossRefPubMedPubMedCentral Nacak H et al (2015) Uric acid is not associated with decline in renal function or time to renal replacement therapy initiation in a referred cohort of patients with Stage III, IV and V chronic kidney disease. Nephrol Dial Transplant 30:2039–2045. doi:10.​1093/​ndt/​gfv225 CrossRefPubMedPubMedCentral
36.
go back to reference Mudaliar S, Polidori D, Zambrowicz B, Henry RR (2015) Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport: from bench to bedside. Diabetes Care 38:2344–2353. doi:10.2337/dc15-0642 CrossRefPubMed Mudaliar S, Polidori D, Zambrowicz B, Henry RR (2015) Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport: from bench to bedside. Diabetes Care 38:2344–2353. doi:10.​2337/​dc15-0642 CrossRefPubMed
38.
go back to reference Briganti EM et al (2002) Smoking is associated with renal impairment and proteinuria in the normal population: the AusDiab kidney study. Australian Diabetes, Obesity and Lifestyle Study. Am J Kidney Dis 40:704–712CrossRefPubMed Briganti EM et al (2002) Smoking is associated with renal impairment and proteinuria in the normal population: the AusDiab kidney study. Australian Diabetes, Obesity and Lifestyle Study. Am J Kidney Dis 40:704–712CrossRefPubMed
Metadata
Title
Mendelian randomization analysis indicates serum urate has a causal effect on renal function in Chinese women
Authors
Jing Liu
Hui Zhang
Zheng Dong
Jingru Zhou
Yanyun Ma
Yuan Li
Qiaoxia Qian
Ziyu Yuan
Juan Zhang
Yajun Yang
Xiaofeng Wang
Xingdong Chen
Hejian Zou
Li Jin
Jiucun Wang
Publication date
01-11-2017
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 11/2017
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-017-1686-8

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