Gender-specific association between uric acid level and chronic kidney disease in the elderly health checkup population in China

Yang, Yanlang; Zhou, Wei; Wang, Yuwei; Zhou, Ru

doi:10.1080/0886022x.2019.1591994

Cited by 29 publications

(22 citation statements)

References 35 publications

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“…compared to female patients in all of the biospecimens we tested. This is consistent with several past studies, where it has been shown that men have higher levels of UA than women in blood and saliva (Andreadou et al, 2009;Kivity et al, 2013;Riis et al, 2018;Yang et al, 2019). The reason for this difference is not clear, but possible explanations include alcohol consumption, which is higher in men, and the influence of estrogens to lower UA (Jung et al, 2018;Yang et al, 2019).…”

Section: Discussionsupporting

confidence: 92%

“…There was no significant difference in plasma UA levels between genders in control subjects, although levels were significantly higher in male compared to female patients in pre-HD and HD subjects ( Figure 1A) consistent with previous studies (Andreadou et al, 2009;Kivity et al, 2013;Riis et al, 2018;Yang et al, 2019). Gender ratios across the three groups of subjects were not significantly different.…”

Section: Plasma Ua In Hd Patientssupporting

confidence: 90%

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Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

et al. 2020

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Oxidative stress has long been implicated in the pathophysiology and progression of Huntington's disease (HD). Uric acid (UA) is a naturally occurring antioxidant that is present in the brain and periphery. Growing evidence has implicated UA as a molecular biomarker for several neurodegenerative diseases, most notably Parkinson's disease (PD). In this study, we investigated UA levels in clinical samples from HD patients and normal controls (NCs) and assessed potential relationships between UA levels and disease and clinical data. UA levels were measured in plasma (n = 107) and saliva (n = 178) samples from premanifest (pre-HD) and manifest HD patients and control subjects. Gender effects of UA levels were observed in both biofluids, with male patients showing higher UA levels compared to female patients. Comparisons of UA levels across diagnostic groups, separated by gender, revealed that both plasma and salivary UA levels were significantly lower in female pre-HD and manifest HD patients compared to NCs. Salivary levels of UA were also significantly lower in male manifest HD patients versus controls, but not in plasma. Correlations of peripheral UA levels to clinical data also showed differences according to gender. In male HD patients, both plasma and salivary UA levels were significantly negatively correlated with total functional capacity (TFC), while positive correlations were observed with total motor score (TMS). Female HD patients showed a significant positive correlation between plasma UA levels and TMS, while salivary UA levels from female patients were significantly correlated to disease burden. Finally, in a separate cohort, we show that UA levels are decreased in postmortem prefrontal cortical samples (n = 20) from HD subjects compared to matched controls. These findings suggest that decreased levels of UA in the brains of HD patients can be reflected in peripheral fluids, with salivary measures of UA particularly offering significant promise as a potentially relevant, non-invasive biomarker of disease symptoms and burden. Our findings further highlight the impact of sexual dimorphism in HD pathophysiology.

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Section: Discussionsupporting

confidence: 92%

Section: Plasma Ua In Hd Patientssupporting

confidence: 90%

Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

et al. 2020

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“…HN is a common secondary kidney disease, associated with renal dysfunction, tubules destruction, and poor prognosis 33 . In this study, we found that hyperuricemic rats developed renal dysfunction, as indicated in elevated serum creatinine, BUN and serum uric acid, and serious glomerulosclerosis and tubular lesions ( Fig.…”

Section: Delayed Administration Of 3-ma Protects Against Renal Dysfunmentioning

confidence: 99%

Delayed treatment with an autophagy inhibitor 3-MA alleviates the progression of hyperuricemic nephropathy

Shi

Tao

et al. 2020

Cell Death Dis

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Autophagy is a cell self-renewal process that relies on the degradation of the cytoplasmic proteins or organelles of lysosomes and is associated with development of numerous diseases. However, the therapeutic effect of autophagy inhibition on hyperuricemic nephropathy (HN) and the underlying mechanisms are still unknown. Here, we investigated the effect of delayed treatment with 3-methyladenine (3-MA), a specific autophagy inhibitor, on the development of HN in a rat model. Administration of 3-MA at 21 days following after uric acid injury protected kidney from hyperuricemic-related injuries, as demonstrated by improving renal dysfunction and architecture damage, blocking Beclin-1 and LC3II/I and decreasing the number of autophagic vacuoles. Late treatment with 3-MA was also effective in attenuating renal fibrosis as evidenced by reducing ECM protein deposition, blocking epithelial-tomesenchymal transition (EMT) and decreasing the number of renal epithelial cells arrested at the G2/M phase of cell cycle. Injury to the kidney resulted in increased expression of TGFβ receptor I, and phosphorylation of Smad3, 3-MA significantly abrogated all these responses. Moreover, inhibition of autophagy suppressed mitochondrial fission, downregulated the expression of Dynamin-related protein 1 (Drp-1), Cofilin and F-actin, and alleviated cell apoptosis. Finally, 3-MA effectively blocked STAT3 and NF-κB phosphorylation and suppressed infiltration of macrophages and lymphocytes as well as release of multiple profibrogenic cytokines/chemokines in the injured kidney. Taken together, these findings indicate that hyperuricemia-induced autophagy is critically involved in the activation of renal fibroblasts, EMT, mitochondrial fission and apoptosis of tubular epithelial cells and development of renal fibrosis. Thus, this study provides evidence for autophagy inhibitors as the treatment of HN patients.

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“…22 Recently, sex differences in associations between uric acid and all-cause mortality or CKD have reported. 23 24 Therefore, in the present study, we evaluated the association between SUA levels and end-stage renal disease (ESRD) development and death in the general adult population in Korea by sex-specific analysis.…”

Section: Introductionmentioning

confidence: 99%

Association between Serum Uric Acid Level and ESRD or Death in a Korean Population

Kim

Son

et al. 2020

J Korean Med Sci

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Background: Serum uric acid (SUA) is recognized as a risk factor for chronic kidney disease (CKD) and mortality. However, there is controversy as to whether a high or low level of SUA is related to the risk of CKD progression or death, and whether it differs between males and females. Methods: We included 143,762 adults who underwent voluntary health screening between 1995 and 2009 in Korea. For each sex, we divided participants into sex-specific quintiles according to SUA levels and compared end-stage renal disease (ESRD) incidence and mortality between the groups with low and high SUA levels and those with middle SUA levels. Sex-specific Cox proportional hazard analyses were performed for ESRD and all-cause mortality. Results: Among the 143,762 participants, 0.2% (n = 272) developed ESRD. The hazard ratio (HR) of ESRD was higher in the highest (adjusted HR, 2.13; 95% confidence interval [CI], 1.18-3.84) and lowest (adjusted HR, 1.90; 95% CI, 1.02-3.51) SUA quintiles than in the middle SUA quintile in males and the highest SUA quintile in females (adjusted HR, 2.31; 95% CI, 1.10-4.84). Four-point three percent (n = 6,215) of participants died during a mean follow-up period of 157 months. The hazard ratio (HR) of all-cause mortality was higher in the highest SUA quintile than in the middle SUA quintile in males (adjusted HR, 1.15; 95% CI, 1.03-1.28) and females (adjusted HR, 1.17; 95% CI, 1.01-1.35). Conclusion: Elevated levels of SUA are associated with increased risk for ESRD and all-cause mortality in both sexes. Low levels of SUA might be related to ESRD and death only in males, showing U-shaped associations. Our findings suggest sex-specific associations between SUA levels and ESRD development and mortality.

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Gender-specific association between uric acid level and chronic kidney disease in the elderly health checkup population in China

Cited by 29 publications

References 35 publications

Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

Uric Acid as a Potential Peripheral Biomarker for Disease Features in Huntington’s Patients

Delayed treatment with an autophagy inhibitor 3-MA alleviates the progression of hyperuricemic nephropathy

Association between Serum Uric Acid Level and ESRD or Death in a Korean Population

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