Abstract: TH-PO1080
Hyperuricemia Robustly Confirmed as a Causal Factor for Incident CKD: Mendelian Randomization Evidence from Large East Asian Cohorts in Taiwan, Japan, and South Korea
Session Information
- CKD: Epidemiology, Risk Factors, and Other Conditions
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Chen, Kuo-Yu, Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Kuo, Chin-Chi, Division of Nephrology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- Chao, Chia-Ter, Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan
- Chen, Hung-Lin, Big Data Center, China Medical University Hospital, Taichung, Taiwan
- Chiang, Hsiu-Yin, Big Data Center, China Medical University Hospital, Taichung, Taiwan
- Lee, Ganghyoung, Ajou University Department of Biological Sciences, Suwon-si, Gyeonggi-do, Korea (the Republic of)
- Johnson, Richard J., University of Colorado Anschutz Medical Campus Department of Medicine, Aurora, Colorado, United States
- Cho, Sungkweon, Ajou University School of Medicine Department of Nephrology, Suwon-si, Gyeonggi-do, Korea (the Republic of)
Background
The causal association between serum uric acid (SUA) levels and incident chronic kidney disease (CKD) has largely been deprioritized by the nephrology community, based on evidence primarily derived from European populations. However, contrary clinical evidence observed in East Asia motivated us to conduct Mendelian randomization research in the largest East Asian population, comprising three countries with a high burden of end-stage kidney disease.
Methods
Using the China Medical University Hospital (CMUH) iHi Platform, we established cohorts for clinical study, two-sample MR (CMUH-2SMR), and one-sample MR (CMUH-1SMR). Hyperuricemia was defined using sex-specific thresholds. We used 2SMR to identify instrumental variables (IVs) of SUA from Taiwan Biobank, BioBank Japan (BBJ), and National Biobank of Korean (KoGES), and assess the causality of SUA on CKD in the CMUH-2SMR Cohort (n=522,641). The primary MR method was the inverse-variance weighting (IVW) approach, supplemented by six sensitivity analyses. A non-linear MR analysis was also conducted in the CMUH-1SMR Cohort (n=36,633).
Results
In the clinical cohort, the median age and SUA level was 51.1-year-old and 5.6 mg/dL. The overall incidence rates of CKD in patients without and with hyperuricemia were 1.28 and 2.21 per 1000 person-months, respectively. Patients with hyperuricemia had a 34% higher risk of developing CKD compared to those without hyperuricemia over the entire follow-up time (adjusted hazard ratio[aHR]: 1.36; 95% CI: 1.29–1.39). A strong causal effect of genetically predicted SUA on incident CKD was observed (odds ratio [OR] from IVW: 1.42 (1.27-1.57) for each 1 SD increase), consistently supported by sensitivity MR methods. The MR analysis adopted IVs from BBJ and KoGES supported the robust causal effect of SUA on CKD, with ORs of 1.18 (95% CI 1.09-1.29) and 1.15 (95 % CI 1.06-1.25), respectively.
Conclusion
The convincingly identified causal relationship between SUA and incident CKD across Taiwan, Japan, and South Korea suggests a need to reevaluate the therapeutic role of hyperuricemia in CKD management, from prevention to progression control, at least within East Asia.