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      Hyperuricemia and its related histopathological features on renal biopsy

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          Abstract

          Background

          Hyperuricemia (HUA) is very common in chronic kidney disease (CKD). HUA is associated with an increased risk of cardiovascular events and accelerates the progression of CKD. Our study aimed to explore the relationship between baseline serum uric acid levels and renal histopathological features.

          Methods

          One thousand seventy patients receiving renal biopsy in our center were involved in our study. The baseline characteristics at the time of the kidney biopsy were collected from Renal Treatment System (RTS) database, including age, gender, serum uric acid (UA), glomerular filtration rate (eGFR), serum creatinine (Cr), urea, albumin (Alb), 24 h urine protein quantitation (24 h-u-pro) and blood pressure (BP). Pathological morphological changes were evaluated by two pathologists independently. Statistical analysis was done using SPSS 21.0.

          Results

          Among 1070 patients, 429 had IgA nephropathy (IgAN), 641 had non-IgAN. The incidence of HUA was 38.8% ( n = 415), 43.8% ( n = 188), and 43.2% ( n = 277) in all patients, patients with IgAN and non-IgAN patients, respectively. Serum uric acid was correlated with eGFR ( r = − 0.418, p < 0.001), Cr ( r = 0.391, p < 0.001), urea ( r = 0.410, p < 0.001), 24-u-pro ( r = 0.077, p = 0.022), systolic blood pressure (SBP) ( r = 0.175, p < 0.001) and diastolic blood pressure (DBP) ( r = 0.109, p = 0.001). Multivariate logistic regression analysis showed that after adjustment for Cr, age and blood pressure, HUA was a risk factor for segmental glomerulosclerosis (OR = 1.800, 95% CI:1.309–2.477) and tubular atrophy/interstitial fibrosis (OR = 1.802, 95% CI:1.005–3.232). HUA increased the area under curve (AUC) in diagnosis of segmental glomerulosclerosis.

          Conclusions

          Hyperuricemia is prevalent in CKD. The serum uric acid level correlates not only with clinical renal injury indexes, but also with renal pathology. Hyperuricemia is an independent risk factor for segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis.

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          Most cited references23

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          Prevalence of Hyperuricemia and Gout in Mainland China from 2000 to 2014: A Systematic Review and Meta-Analysis

          We systematically identified the prevalence of hyperuricemia and gout in mainland China and provided informative data that can be used to create appropriate local public health policies. Relevant articles from 2000 to 2014 were identified by searching 5 electronic databases: PubMed, Google Scholar, Chinese Wanfang, CNKI, and Chongqing VIP. All of the calculations were performed using the Stata 11.0 and SPSS 20.0 software. The eligible articles (n = 36; 3 in English and 33 in Chinese) included 44 studies (38 regarding hyperuricemia and 6 regarding gout). The pooled prevalence of hyperuricemia and gout was 13.3% (95% CI: 11.9%, 14.6%) and 1.1% (95% CI: 0.7%, 1.5%), respectively. Although publication bias was observed, the results did not change after a trim and fill test, indicating that that impact of this bias was likely insignificant. The prevalence of hyperuricemia and gout was high in mainland China. The subgroup analysis suggested that the geographical region, whether the residents dwell in urban or rural and coastal or inland areas, the economic level, and sex may be associated with prevalence.
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            Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system.

            Plasma uric acid has been associated with hypertension in a variety of disorders, and has been shown to be predictive of hypertension. The mechanistic role of uric acid in the development of hypertension is not known however. We tested the hypothesis that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation and oxidative stress by stimulating the vascular renin-angiotensin system (RAS). Rat VSMC were exposed to 0-300 micromol uric acid for 48 h. Uric acid (200 and 300 micromol) stimulated the proliferation of VSMC as measured by thymidine uptake. This effect was prevented by 10(-6) mol losartan or by 10(-6) mol captopril. Incubation of VSMC with uric acid for 48 h also increased angiotensinogen messenger RNA expression and intracellular concentrations of angiotensin II. These responses were also inhibited by losartan and captopril. Increased expression of angiotensinogen mRNA was also inhibited by co-incubation with PD 98059, a mitogen-activated protein (MAP) kinase inhibitor. Uric acid stimulated the production of hydrogen peroxide and 8-isoprostane in VSMC. These increases in oxidative stress indicators were significantly reduced by co-incubating the cells with captopril or losartan. Uric acid also decreased nitrite and nitrate concentrations in the culture medium, an effect that was prevented by losartan and captopril. These results demonstrate that uric acid stimulates proliferation, angiotensin II production, and oxidative stress in VSMC through tissue RAS. This suggests that uric acid causes cardiovascular disorders by stimulating the vascular RAS, and this stimulation may be mediated by the MAP kinase pathway.
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              Elevated uric acid increases the risk for kidney disease.

              Recent epidemiologic studies suggest that uric acid predicts the development of new-onset kidney disease, but it is unclear whether uric acid is an independent risk factor. In this study, data from 21,475 healthy volunteers who were followed prospectively for a median of 7 yr were analyzed to examine the association between uric acid level and incident kidney disease (estimated GFR [eGFR] or =9.0 mg/dl) was associated with a tripled risk (odds ratio 3.12; 95% confidence interval 2.29 to 4.25). These increases in risk remained significant even after adjustment for baseline eGFR, gender, age, antihypertensive drugs, and components of the metabolic syndrome (waist circumference, HDL cholesterol, blood glucose, triglycerides, and BP). In a fully adjusted spline model, the risk for incident kidney disease increased roughly linearly with uric acid level to a level of approximately 6 to 7 mg/dl in women and 7 to 8 mg/dl in men; above these levels, the associated risk increased rapidly. In conclusion, elevated levels of uric acid independently increase the risk for new-onset kidney disease.
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                Author and article information

                Contributors
                fsl0311@163.com
                zhangping415@126.com
                awang@georgeinstitute.org.au
                xwang@georgeinstitute.org.au
                scwangli62@163.com
                guisenli@163.com
                hongdaqing11@126.com
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                18 March 2019
                18 March 2019
                2019
                : 20
                : 95
                Affiliations
                [1 ]ISNI 0000 0004 0369 4060, GRID grid.54549.39, Renal Department and Nephrology Institute, Sichuan Provincial People’s Hospital, School of Medicine, , University of Electronic Science and Technology of China, ; Chengdu, 610072 China
                [2 ]ISNI 0000 0004 4902 0432, GRID grid.1005.4, The George Institute for Global Health, , University of NSW, ; Missenden Road, PO Box M201, Sydney, NSW 2050 Australia
                [3 ]Department of Renal Medicine, Northern Beaches Hospital, Sydney, NSW 2086 Australia
                [4 ]ISNI 0000 0004 1798 4472, GRID grid.449525.b, North Sichuan Medical College, ; Nanchong, 637000 China
                Article
                1275
                10.1186/s12882-019-1275-4
                6423852
                30885171
                b4a95274-822a-4726-80d5-f7bafefe554b
                © The Author(s). 2019

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 4 May 2018
                : 3 March 2019
                Funding
                Funded by: Health and Family Planning Commission of Sichuan Province Research Project
                Award ID: 17PJ062
                Funded by: Youth Science and Technology Creative Research Groups of Sichuan Province
                Award ID: 2015TD0013
                Funded by: Sichuan Science and Technology Department support project
                Award ID: 2015SZ0245
                Funded by: National Heart Foundation post-doctoral fellowship
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2019

                Nephrology
                hyperuricemia,histopathological features,chronic kidney disease
                Nephrology
                hyperuricemia, histopathological features, chronic kidney disease

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