Genetically Elevated Serum Uric Acid and Renal Function in an Apparently Healthy Population

Abstract

Background: The association between uric acid and kidney disease has been extensively investigated. Numerous studies have reported the association between circulating levels of uric acid and renal function. Objectives: To test, by the Mendelian randomization method, whether there is a causal association between circulating levels of uric acid and renal function. Methods: In 989 participants, estimated glomerular filtration rate (eGFR) was calculated, the circulating level of uric acid was tested, and the uric acid polymorphism (rs11722228) was genotyped. Results: After adjusting for age, gender, smoking history, alcohol intake, antihypertensive medication, body mass index, waist-to-hip ratio, and levels of urea nitrogen and creatinine, a significant allelic difference was found in uric acid levels for each genotype (p < 0.0001). Furthermore, the circulating levels of uric acid were negatively associated with eGFR after adjusting for cardiovascular risk factors and other potential confounders (p < 0.0001). Meanwhile, eGFR was significantly associated with the genotypes of rs11722228 (β = -0.07; p = 0.02). Conclu-sions: Evidence from the Mendelian randomization approach implied a causal relationship between uric acid and renal function in an apparently healthy population.

Hyperuricemia in Kidney Disease: A Major Risk Factor for Cardiovascular Events, Vascular Calcification, and Renal Damage

“…In contrast, Mendelian randomization studies based on using genetic scores from gene polymorphisms affecting serum urate levels in the general population have failed to show a relationship of serum urate with CKD, while the association with gout is strong [31,80,81], with one exception [82]. While these studies have often been interpreted to show that serum urate does not have a causal role in CKD, there are other potential explanations.…”

Uric acid and risk of pre-eclampsia: results from a large case–control study and meta-analysis of prospective studies

“…Nevertheless, there is evidence to favour evaluating a causal effect of uric acid in pre-eclampsia. Knowledge of the genetics of uric acid metabolism 38 , 39 would support a Mendelian randomisation study in pregnant women. This has been done for the association between uric acid and other outcomes 40 – 42 and could help determine whether uric acid is a causative factor in pre-eclampsia.…”

Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011–2020

“…Model 3 additionally considered eGFR (estimated glomerular filtration rate), obesity (body mass index [BMI] ≥25 for Asian or BMI ≥30 for other ethnicities, nonobese), and other components of metabolic syndrome. eGFR, calculated using the Modification of Diet in Renal Disease equations, eGFR = 175 × (serum creatinine) −1.154 × (age) −0.203 × 0.742 [if female] × 1.212 [if Black]), 20 has a known negative correlation with SUA levels, necessitating adjustment 21,22 . We further explored the interaction between metabolic syndrome components and ethnicity by adding an interaction term in regression models.…”

“…Model 1 includes 20 has a known negative correlation with SUA levels, necessitating adjustment. 21,22 We further explored the interaction between metabolic syndrome components and ethnicity by adding an interaction term in regression models. Post hoc analyses, using adjusted Wald tests, were performed to assess ethnic differences in multiplicative interactions.…”