Sex Difference in the Associations among Hyperuricemia with New-Onset Chronic Kidney Disease in a Large Taiwanese Population Follow-Up Study

Abstract

The global prevalence and incidence of chronic kidney disease (CKD) continue to increase. Whether hyperuricemia is an independent risk factor for renal progression and whether there are sex differences in the relationships between serum uric acid (UA) and a decline in renal function are unclear. Therefore, in this longitudinal study, we aimed to explore these relationships in a large cohort of around 27,000 Taiwanese participants in the Taiwan Biobank (TWB), and also to identify serum UA cutoff levels in men and women to predict new-onset CKD. A total of 26,942 participants with a median 4 years of complete follow-up data were enrolled from the TWB. We excluded those with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) at baseline (n = 297), and the remaining 26,645 participants (males: 9356; females: 17,289) were analyzed. The participants who developed CKD during follow-up were defined as having incident new-onset CKD, and those with a serum UA level >7 mg/dL in males and >6 mg/dL in females were classified as having hyperuricemia. After multivariable analysis, hyperuricemia (odds ratio [OR], 2.541; 95% confidence interval [CI], 1.970–3.276; p < 0.001) was significantly associated with new-onset CKD. Furthermore, in the male participants (n = 9356), hyperuricemia (OR, 1.989; 95% CI, 1.440–2.747; p < 0.001), and quartile 4 of UA (vs. quartile 1; OR, 2.279; 95% CI, 1.464–3.547; p < 0.001) were significantly associated with new-onset CKD, while in the female participants (n = 17,289), hyperuricemia (OR, 3.813; 95% CI, 2.500–5.815; p < 0.001), quartile 3 of UA (vs. quartile 1; OR, 3.741; 95% CI, 1.250–11.915; p = 0.018), and quartile 4 of UA (vs. quartile 1; OR, 12.114; 95% CI, 14.278–34.305; p < 0.001) were significantly associated with new-onset CKD. There were significant interactions between hyperuricemia and sex (p = 0.024), and quartiles of serum UA and sex (p = 0.010) on new-onset CKD. Hyperuricemia was associated with new-onset CKD in the enrolled participants, and the interactions between hyperuricemia and sex were statistically significant. Hyperuricemia was more strongly associated with new-onset CKD in the women than in the men.

Insufficient compensatory pancreatic β-cells function might be closely associated with hyperuricemia in U.S. adults: evidence from the National Health and Nutrition Examination Survey

“…Metabolic changes during the menopause may lead to increased SUA levels in women [ 37 ], and epidemiological studies have also shown a positive association between SUA and insulin resistance in older women, but not in men [ 38 ]. Consistent with this gender difference, many studies have found that serum uric acid levels are more strongly associated with disease in women, including chronic kidney disease [ 39 ] and coronary heart disease [ 37 ]. More research is needed into the sex-specific role of β -cells function in HUA.…”

Association between dietary patterns and chronic kidney disease combined with hyperuricemia

“…Previous studies indicated that elevated serum UA was an independent predictor for the development of CKD. 31 The underlying mechanism between UA and CKD risk are as follows: (1) UA induces hypertension by affecting endothelial function and reducing nitric oxide production; 32 (2) hyperuricemia triggers the activation of the renin-angiotensin-aldosterone system, leading to renal vasoconstriction and reduced renal plasma flow; 33 (3) UA may increase oxidative stress, leading to mitochondrial dysfunction, over-secretion of proinflammatory cytokines, and proliferation of vascular smooth muscle cells; 6 and (4) UA crystals can cause tubular damage through inflammation mediated by direct physical mechanisms. 6 Diet has also been implicated in the risk of CKD 25,34 and hyperuricemia.…”

Serum uric acid is associated with chronic kidney disease in elderly Chinese patients with diabetes

“…A separate significant finding worth noting was that the association between hyperuricemia and the new onset of CKD in males was relatively stronger than that in females, with the adjusted HR of hyperuricemia for CKD being 1.925 (1.724–2.150) and 1.676 (1.530–1.848) for males and females, respectively. Previous studies have investigated sex differences in the correlations between hyperuricemia and incident CKD but obtained mixed results [ 13 , 42 , 43 ]. Estrogen is the most commonly considered reason for this sex difference, as it can cause the excretion of urate through urine [ 44 ] and inhibit the generation of uric acid by xanthine oxidase [ 45 ].…”