High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes

Ficociello, Linda H.; Rosolowsky, Elizabeth; Niewczas, Monika A.; Maselli, Nicholas J.; Weinberg, Janice; Aschengrau, Ann; Eckfeldt, John H.; Stanton, Robert C.; Gałecki, Andrzej T.; Doria, Alessandro; Warram, James H.; Królewski, Andrzej S.

doi:10.2337/dc10-0227

Cited by 206 publications

(168 citation statements)

References 26 publications

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“…These results are in keeping with studies of rats, where hyperuricemia has been shown to induce renal arteriopathy and renal damage, 10,21 although our data cannot establish causality or confirm that this has occurred in our patients. 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.…”

Section: Discussionsupporting

confidence: 81%

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: Discussionsupporting

confidence: 81%

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

et al. 2013

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“…Another report provided evidence for a clear dose-response relationship between SUA levels and early glomerular filtration rate (GFR) loss in patients with T1DM. The progression and regression of urinary albumin excretion were not associated with UA levels [60] . These studies show that UA is an in- (especially exercise time until ST depression) when a high dose of 600 mg/d of allopurinol was administered to patients with chronic stable angina [76] .…”

Section: Nephropathymentioning

confidence: 94%

“…Through inhibition of XDH/XO activity, cytokine-induced neudependent risk factor for renal dysfunction, even after adjustments for confounding factors. Furthermore, even high-normal SUA levels accelerated renal dysfunction in T2DM patients [17,[59][60][61][62] . UA is lowered in diabetes mellitus (DM) due to hyperfiltration [50] , but decreased UA excretion during renal dysfunction raises SUA levels.…”

Section: Atherosclerosis and Xdh/xo In Monocytes/macrophagesmentioning

confidence: 99%

Linking uric acid metabolism to diabetic complications

Kushiyama

Tanaka

Hara

et al. 2014

WJD

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Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase (XDH/ XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid (UA) generation inhibitor in the 1950s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target for vascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Uric acid; Xanthine dehydrogenase/xanthine oxidase; Diabetes mellitus; Diabetic complications; Xanthine oxidase inhibitor; Metabolism Core tip: Uric acid (UA) is derived from essential metabolism, and UA metabolism is becoming a novel risk and interventional factor of lifestyle-related diseases in this obesity-prone era. The relationship between UA metabolism and diabetic complications is highlighted in this review and supposed molecular mechanisms are mentioned.Kushiyama A, Tanaka K, Hara S, Kawazu S. Linking uric acid metabolism to diabetic complications. World J Diabetes 2014; 5(6): 787-795 Available from:

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“…Similarly, in a retrospective study analyzing 223 patients with Ig A nephropathy, hyperuricemia was observed in association with an increased risk of progression of the chronic kidney disease [39] but was no longer statistically significant after adjustment for Confounding factors. Nevertheless, uric acid may have an independent role in the development of tubulo-interstitial lesions and contribute to inflammation in the renal parenchyma observed in these patients [40] as in other chronic glomerulopathies [41]. Thus, although hyperuricemia may be a consequence of a pre-existing kidney disease, these results show the involvement of uric acid in renal diseases.…”

Section: Discussionmentioning

confidence: 60%

Hyperuricemia in Patients with Chronic Renal Failure in the General Hospital of National Reference of N’Djamena (Chad)

Abderraman¹,

Hamat²,

Tondi³

et al. 2017

OJNeph

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Introduction: Hyperuricemia is defined as a level of serum uric acid greater than or equal to 70 mg/l (420 μmol/l) in men and 60 mg/l (360 μmol/l) in women. Several studies have shown that it is a risk factor or a factor of progression of chronic kidney disease. Recent experimental and epidemiological data correlate the association of hyperuricemia with chronic kidney disease (CKD), arterial hypertension and cardiovascular diseases, thus raising the question of the usefulness of therapeutics in the prevention of renal diseases. The objective of this study is to seek a link between chronic kidney disease and hyperuricemia. Materials and Methods: This is a descriptive and analytical study conducted at hemodialysis unit and cardiology service of General Hospital of National reference of N'Djamena (Chad) from 1 th January to 1 th October 2013 (10 months). We included all chronic kidney disease patients hospitalized in hemodialysis unit and cardiology service who presented associated hyperuricemia. Results: There were 712 CKD patients who were hospitalized. Among them, there were 108 patients who were included in the study and who had hyperuricemia as a prevalence of 15.20%. The average age of patients was 35.5 years and the sex ratio was 3/1. The age group between 40 to 60 years represented 54.6%. There were 41.7% of traders. Hypertensive patients accounted for 49.1%; association of diabetes and hypertension was noted in 12.90%. Renal insufficiency was moderate in 43.5% of patients. Hyperuricemia was present in more than 90% of patients. Profession, age, hematuria, proteinuria and hypertension were statistically positively related to 10hyperuricemia. Treatment consisted of prescribing allopurinol in 84% of patients. In more than 11% of patients the progression was unfavorable. Conclusion: The implication of hyperuricemia in chronic kidney disease has been proved in several recent studies. However, randomized studies at very long scales have to be carried out to conclude from its real impact on the prevention and treatment of chronic kidney disease.

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High-Normal Serum Uric Acid Increases Risk of Early Progressive Renal Function Loss in Type 1 Diabetes

Cited by 206 publications

References 26 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

Linking uric acid metabolism to diabetic complications

Hyperuricemia in Patients with Chronic Renal Failure in the General Hospital of National Reference of N’Djamena (Chad)

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