Ethnic disparities in bidirectional causal effects between serum uric acid concentrations and kidney function: Trans-ethnic Mendelian randomization study

Abstract

Introduction: Researchers have investigated the causal effect between serum uric acid (SUA) concentrations and kidney function for decades, but studies produced inconsistent results. This study aimed to clarify the bidirectional causal effects between SUA concentrations and kidney function and to explore the potential ethnic disparities by conducting a trans-ethnic Mendelian randomization study in European, African, and Asian ancestries. Materials and methods: The summary-level data for this study were obtained from the Global Urate Genetics Consortium, CKDGen Consortium, UK Biobank, and Japan Biobank for different outcomes and exposures, respectively. The traits of kidney function were estimated glomerular filtration rate from serum creatinine (eGFRcr), estimated glomerular filtration rate from cystatin C (eGFRcys), and blood urea nitrogen (BUN). Using the multiplicative random-effects inverse variance weighting mode, our primary analysis produced robust results despite heterogeneity. Additionally, we performed the Mendelian randomization pleiotropy residual sum and outlier test to eliminate the horizontal pleiotropy and obtain accurate results. Results: Our findings revealed that elevated SUA concentrations had causal effects on declined eGFRcys, BUN, and a diagnosis of chronic kidney disease in European ancestries and eGFRcr in Asian ancestries. Additionally, the causal effects of declined eGFRcr and elevated BUN concentrations on elevated SUA concentrations were observed in both European and Asian ancestries. However, no bidirectional causal effect was found between SUA concentrations and eGFRcr among African ancestries. Conclusions: This trans-ethnic Mendelian randomization study confirmed the bidirectional causal effects between SUA concentrations and kidney function and highlighted the importance of considering ethnic disparities in clinical treatments.

Keywords

• Uric acid
• chronic kidney disease
• Mendelian randomization study