A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function

Kanbay, Mehmet; Huddam, Bülent; Azak, Alper; Solak, Yalçın; Kadioglu, Gulay Kocak; Kırbaş, İsmail; Duranay, Murat; Covic, Adrian; Johnson, Richard J.

doi:10.2215/cjn.11451210

Cited by 230 publications

(186 citation statements)

References 44 publications

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“…However, our findings are in keeping with previous studies showing a relationship between serum uric acid level and progression of renal disease in patients with type 1 diabetes mellitus, 22 in normotensive blood donors, 23 and a recent study showing an improvement in renal function after administration of rasburicase in elderly patients with hyperuricemia. 24 Small interventional trials have also shown improvement in renal function after allopurinol treatment in patients with both normal renal function 25 and CKD. 26 This supports our findings and suggests uric acid reduction may prevent decline in renal function, however larger studies with longer follow-up are required.…”

Section: Discussionmentioning

confidence: 99%

Serum Uric Acid Level, Longitudinal Blood Pressure, Renal Function, and Long-Term Mortality in Treated Hypertensive Patients

et al. 2013

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There are a plethora of epidemiological studies linking uric acid with incident hypertension [1][2][3][4] and with cardiovascular events. 5 Some studies have shown a sex difference in cardiovascular events with the adverse cardiovascular association of uric acid seen only in women. [6][7][8] There is convincing evidence from animal studies that elevated uric acid has a detrimental effect on blood pressure (BP) and renal function. Administration of uric acid causes a rise in arterial BP in rat models 9 and sustained elevation of uric acid results in salt-sensitive hypertension and irreversible renal damage characterized by both arteriolar and glomerular damage. 10 Furthermore, the xanthine oxidase inhibitor allopurinol lowers BP in adolescents with hypertension and hyperuricemia 11 and both allopurinol and the uricosuric drug probenecid lower BP in obese adolescents with prehypertension. 12 A recent meta-analysis found that allopurinol lowers BP by 3/2 mm Hg in adults, 13 although this has never been tested in a specifically designed prospective study. Despite these results, there is still debate about a causal role for uric acid and the potential cardiovascular benefits of allopurinol may reflect either uric acid reduction or other mechanisms, such as superoxide anion reduction. 14 The association of uric acid with BP and kidney function suggests that uric acid levels may have implications in the clinical management of hypertension. The aim of this study is to determine whether baseline uric acid level, in patients attending a hypertension clinic, is associated with longitudinal BP level, renal function, and long-term cause-specific mortality in a sex-specific manner. Methods Study Setting and Study PopulationWe performed an analysis of longitudinal BP control, change in renal function, and long-term cause-specific mortality using data from the Glasgow Blood Pressure Clinic (GBPC).Abstract-Uric acid may have a role in the development of hypertension and renal dysfunction. We explored the relationship among longitudinal blood pressure, renal function, and cardiovascular outcomes in a large cohort of patients with treated hypertension. We used data from the Glasgow Blood Pressure Clinic database. Patients with a baseline measure of serum uric acid and longitudinal measures of blood pressure and renal function were included. Mortality data were obtained from the General Register Office for Scotland. Generalized estimating equations were used to explore the relationship among quartiles of serum uric acid, blood pressure, and estimated glomerular filtration rate. Cox proportional hazard models were developed to assess mortality relationships. In total, 6984 patients were included. Serum uric acid level did not influence the longitudinal changes in systolic or diastolic blood pressure but was related to change in glomerular filtration rate. In comparison with patients in the first quartile of serum uric acid, the relative decrease in glomerular filtration rate in the fourth was 10.7 (95% confidence interval, 7.9-13.6 ...

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Section: Discussionmentioning

confidence: 99%

Serum Uric Acid Level, Longitudinal Blood Pressure, Renal Function, and Long-Term Mortality in Treated Hypertensive Patients

et al. 2013

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“…Other clinical studies have also demonstrated that lowering uric acid benefited inflammation, endothelial function, blood pressure and insulin resistance (25)(26)(27). These studies demonstrated that uric acid induced an inflammatory response and inflammatory cell infiltration in numerous ways.…”

Section: Discussionmentioning

confidence: 84%

“…However, SUA levels were associated with greater severity of lobular inflammation and NASH. Others studies demonstrated that uric acid induced inflammation and inflammatory cell infiltration in a variety of ways (25)(26)(27). Repeated inflammation leads to liver fibrosis suggesting that hyperuricemia was indirectly involved in liver fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease

Huang

Zhang

et al. 2016

Biomedical Reports

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Abstract. Hyperuricemia is significantly associated with and independently predicts the risk for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to examine the association of serum uric acid (SUA) levels with liver histology in patients with biopsy-proven NAFLD. Data were collected from 158 adults aged >18 years, and diagnosed with biopsy-proven NAFLD. The differences in liver histology were assessed between hyperuricemic and normal SUA groups with NAFLD to determine the possible risk factors. The SUA level was closely associated with the degree of steatosis (correlation coefficient 0.177, P= 0.027). A higher proportion of patients with hyperuricemia showed increased severity of lobular inflammation (lobular inflammation score ≥2) compared with patients exhibiting normal SUA (75 vs. 52.7%; χ 2 =8.548, P=0.003). Hyperuricemic groups had higher non-alcoholic steatosis (≥5) compared to the normal SUA groups with NAFLD (48.8 vs. 31.1%; χ 2 =5.131, P=0.024). Hyperuricemia was independently associated with advanced lobular inflammation (odds ratio, 2.79; 95% confidence interval, 1.250-6.257; P= 0.012) using a logistic regression model controlling for ferritin, serum alanine aminotransferase and aspartate aminotransferase. In conclusion, hyperuricemia is associated with histologically severe NAFLD. Hyperuricemia was independently associated with greater odds of advanced lobular inflammation of NAFLD. IntroductionNon-alcoholic fatty liver disease (NAFLD) is a state of intrahepatic fat accumulation, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is the most common liver disease in Western countries, affecting 20-30% of the general population (1). NAFLD is also an emerging public health concern in developing countries (2,3). Among more affluent regions of China, the community prevalence of NAFLD is 15% (2). With the increasing obesity pandemic, the prevalence of NAFLD is likely to increase in the future (2). Serum uric acid (SUA) levels are closely associated with insulin resistance, diabetes mellitus type 2 and metabolic syndrome (4,5). Hyperuricemia was significantly associated with NAFLD, and the prevalence of NAFLD increases with SUA increase (6-8). Elevation in SUA levels independently predicts an increase in the risk for the incident of NAFLD and suggests that high SUA levels may have a causal role in the development of NAFLD (9). Certain in vitro and in vivo studies in hepatocytes and liver tissue of mice suggest that uric acid stimulated fat synthesis and induced inflammatory cell infiltration in the liver (10,11). Therefore, it is plausible that uric acid may reflect increased disease severity in NAFLD. However, there is one previous study regarding the association between UA serum levels and histological severity of NAFLD patients (12). The majority of studies have been conducted in Western populations. Notably, the prevalence of obesity in China is significantly lower compared to Western countries (13,14), and certain features of metabolic ...

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“…At low levels, Allopurinol competitively inhibits xanthine oxidase by acting as a substrate, however, at increased levels, it acts as a non-competitive inhibitor [68]. The accidental discovery of the role of xanthine oxidase in the production of superoxide, paved the way for more research in this area for development of several other potent xanthine oxidase inhibitors of different classes and the exploration of potential anti-oxidant effect of Allopurinol [69][70][71][72][73][74][75][76][77][78][79][80][81][82][83][84][85][86]. Apart from its established use in gout and tumor lysis syndrome, the pleiotropic effects of Allopurinol is being explored in a number of conditions [67].…”

Section: The Therapeutic Potential Of Allopurinolmentioning

confidence: 99%

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

Singh¹,

Farrington²

2015

J Diabetes Metab

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Vascular calcification contributes significantly to the vascular damage burden in type 2 diabetes. Chronic hyperglycaemia is the driver of initiation and progression of vascular damage in these subjects. Enhanced oxidative stress is widespread in these subjects due to complex metabolic, cytokine, inflammatory and ageing factors, on the background of chronic hyperglycaemia. All these factors together contribute to an increased risk of vascular damage leading to atherosclerosis and vascular calcification. The xanthine oxidase system is a major contributor to the development of enhanced oxidative stress through generation of excessive free radicals. Current standard therapy is focused on controlling hyperglycaemia and screening/treatment of known co-morbidities. However, these therapies do not target oxidative stress. Allopurinol, a potent xanthine oxidase inhibitor has demonstrated beneficial effects on several parameters of vascular health such as reduction in oxidative stress, proteinuria, reversal of vascular damage, regression of ventricular hypertrophy and arresting the rate of progression of chronic kidney disease. A randomised clinical trial of Allopurinol for amelioration of oxidative stress, endothelial cell dysfunction and vascular calcification in subjects with type 2 DM may be helpful to explore its potential in this area.

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A Randomized Study of Allopurinol on Endothelial Function and Estimated Glomular Filtration Rate in Asymptomatic Hyperuricemic Subjects with Normal Renal Function

Cited by 230 publications

References 44 publications

Serum Uric Acid Level, Longitudinal Blood Pressure, Renal Function, and Long-Term Mortality in Treated Hypertensive Patients

Serum Uric Acid Level, Longitudinal Blood Pressure, Renal Function, and Long-Term Mortality in Treated Hypertensive Patients

Association of the serum uric acid level with liver histology in biopsy-proven non-alcoholic fatty liver disease

Vascular Calcification in Type 2 Diabetes: A Role for Allopurinol?

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