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

Abstract

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. 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. 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 65years 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. 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.