Is Uric Acid Excretion A Possible Cause of Chronic Kidney Disease? A Cross-Sectional Study of CHNS with Mendelian Randomization Verification

Introduction and Objective: To explore whether uric acid excretion (UAE) causes chronic kidney disease (CKD). Methods: A cross-sectional study was conducted using China health and nutrition survey (CHNS) dataset. The relationship between fractional excretion of uric acid (FEUA) and CKD was performed using univariate and multivariate logistic regression analysis. Two sets of TSMR analyses were performed for verification using UAE up/down regulation single-nucleotide polymorphisms (SNPs) retrieved by searching the available GWAS studies. Cochran’s Q test, MR-Egger intercept, MR-PRESSO, power calculation, and sample overlap analysis were performed. α=0.05, two sided. Results: Logistic regression analysis revealed that FEUA was significantly and independently associated with CKD after adjusting for confounding factors (OR: 1.723, CI: 1.523-1.949, P<0.001). In the first TSMR set, originally, OR of UAE elevation in CKD was higher than 1, but failed to achieve significance (OR = 1.008, 95% CI: 0.976-1.041, P= 0.629, power =0.344), aligning all SNPs to UAE elevation direction achieved significant causal effect (OR = 1.025, 95% CI: 1.002-1.049, P= 0.033). In the 2nd TSMR set, a significant protective relationship was found between UAE decrease and CKD (OR = 0.9538, 95% CI: 0.9210-0.9877, P= 0.008, Power=0.401). Pleiotropy (MR-Egger intercept, -0.0070, P= 0.7810), outliers (global test RSS=1.7621, P=0.9370), and heterogeneity (IVW Q= 1.2236, P= 0.9426) were not identified. Type 1 error rate with sample overlap was less than 0.05. Conclusion: This study demonstrated that FEUA is independently and positively associated with CKD and that UAE decrease plays a causal protective role against CKD, while UAE elevation causally promotes CKD, underscoring the importance of monitoring kidney damage in T2DM patients by early detection of fractional excretion of uric acid. Disclosure: L. Zhuo: None. L. Zhou: None. X. Han: None. Funding: This study was funded by the National Natural Science Foundation of China (Grant No.: 82170814) and National Major Science and Technology Project of China (Grant No.2024ZD0530204). This work is also funded by the 2024 National Key Clinical Specialty Discipline Construction Program of China (Department of Endocrinology, Peking University People's Hospital) with support from the central government budget. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.