Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort

Iseki, Kunitoshi; Ikemiya, Yoshiharu; Inoue, Taku; Iseki, Chiho; Kinjo, Kozen; Takishita, Shuichi

doi:10.1053/j.ajkd.2004.06.006

Cited by 312 publications

(169 citation statements)

References 36 publications

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“…7 In our study, we noted a significant risk for incident kidney disease associated with higher uric acid levels in women and a trend in men; however, the interaction between gender and uric acid was NS, indicating that this result was statistically comparable in both men and women.…”

Section: Discussionmentioning

confidence: 44%

Uric Acid and Incident Kidney Disease in the Community

Weiner¹,

Tighiouart

Elsayed³

et al. 2008

Journal of the American Society of Nephrology

400

299

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Uric acid may mediate aspects of the relationship between hypertension and kidney disease via renal vasoconstriction and systemic hypertension. To investigate the relationship between uric acid and subsequent reduced kidney function, limited-access data of 13,338 participants with intact kidney function in two community-based cohorts, the Atherosclerosis Risks in Communities and the Cardiovascular Health Study, were pooled. Mean baseline serum uric acid was 5.9 Ϯ 1.5 mg/dl, mean baseline serum creatinine was 0.9 Ϯ 0.2 mg/dl, and mean baseline estimated GFR was 90.4 Ϯ 19.4 ml/min/1.73 m 2 . During 8.5 Ϯ 0.9 yr of follow-up, 712 (5.6%) had incident kidney disease defined by GFR decrease (Ն15 ml/min/1.73 m 2 with final GFR Ͻ60 ml/min/1.73 m 2 ), while 302 (2.3%) individuals had incident kidney disease defined by creatinine increase (Ն0.4 mg/dl with final serum creatinine Ͼ1.4 mg/dl in men and 1.2 mg/dl in women). In GFR-and creatinine-based logistic regression models, baseline uric acid level was associated with increased risk for incident kidney disease (odds ratio 1.07 [95% confidence interval 1.01 to 1.14] and 1.11 [95% confidence interval 1.02 to 1.21] per 1-mg/dl increase in uric acid, respectively), after adjustment for age, gender, race, diabetes, systolic BP, hypertension, cardiovascular disease, left ventricular hypertrophy, smoking, alcohol use, education, lipids, albumin, hematocrit, baseline kidney function and cohort; therefore, elevated serum uric acid level is a modest, independent risk factor for incident kidney disease in the general population.

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Section: Discussionmentioning

confidence: 44%

Uric Acid and Incident Kidney Disease in the Community

Weiner¹,

Tighiouart

Elsayed³

et al. 2008

Journal of the American Society of Nephrology

400

299

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“…We have hypothesized that the ratio of XO over XOR increases in accordance with renal dysfunction in oxidative condition such as plasma. In this context, the progress of CKD among subjects with hyperuricemia [26][27][28] might be explained by the profound elevation of XO/XOR ratio.…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Xanthine Oxidoreductase and Xanthine Oxidase Activities in Plasma and Kidney Dysfunction

Terawaki¹,

Murase²,

Nakajima³

et al. 2017

J Clin Exp Nephrol

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Background: Oxidative stress (OS) is thought to play a role in detrimental events among patients with chronic kidney disease (CKD). Although the mechanism of OS increases in CKD patients is unclear, it has been suggested that increased activity of xanthine oxidase (XO), the superoxideproducing form of xanthine oxidoreductase (XOR), plays a large role in enhancing OS. Therefore, we measured the activities of plasma XOR and XO among CKD patients.

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“…The observed effect of increased UA levels on OR for development of new-onset kidney disease is increasing rapidly with each hypertension group and is more pronounced in women, a finding that is supported by studies concerning the early detection of renal disease and its progression to ESRD. 15,35 Noteworthy, mild hyperuricemia was shown to be associated with renal damage in untreated primary hypertension. 36 All in all, we assume that the findings of the stratified spline analyses seem to be substantial from a public health viewpoint, because in the general adult population the prevalence of prehypertension and hypertension is approximately 60%, 37 and the prevalence of hyperuricemia (defined as UA Ͼ6.0 mg/dl in women and UA Ͼ7.0 mg/dl in men) is approximately 17%.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, hyperuricemia is associated with a greater incidence of ESRD. 15 Findings from experimental animal and cell biologic studies support the suggested nephrotoxicity of elevated UA levels: UA plays a role in platelet adhesiveness 16 ; hyperuricemia may be one of the key mechanisms for the activation of the renin-angiotensin and cyclooxygenase-2 systems in progressive renal disease, which could be mediated by its effect to upregulate angiotensin-1 receptors on vascular smooth muscle cells 17,18 ; oxonic acid induced-hyperuricemia induced systemic hypertension, glomerular hypertrophy/hypertension, afferent arteriolar sclerosis, and macrophage infiltration in the rat kidney 8 ; hyperuricemia induced arteriolopathy of preglomerular vessels, which impairs the autoregulatory response of afferent arterioles, resulting in glomerular hypertension, and lumen obliteration induced by vascular wall thickening produces severe renal hypoperfusion 19 ; direct entry of UA into both endothelial and vascular smooth muscle cells results in local inhibition of endothelial nitric oxide levels, stimulation of vascular smooth muscle cell proliferation, and stimulation of vasoactive and inflammatory mediators. 20 The aim of this study was to provide epidemiologic evidence for hyperuricemia as a potential independent risk factor for the development of new-onset kidney disease; therefore confounder models using mixed-effect models with increasing levels of UA were fitted.…”

mentioning

confidence: 99%

Elevated Uric Acid Increases the Risk for Kidney Disease

Obermayr¹,

Temml²,

Gutjahr³

et al. 2008

Journal of the American Society of Nephrology

550

362

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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] Ͻ60 ml/min per 1.73 m 2 ). After adjustment for baseline eGFR, a slightly elevated uric acid level (7.0 to 8.9 mg/dl) was associated with a nearly doubled risk for incident kidney disease (odds ratio 1.74; 95% confidence interval 1.45 to 2.09), and an elevated uric acid (Ն9.0 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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Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort

Cited by 312 publications

References 36 publications

Uric Acid and Incident Kidney Disease in the Community

Uric Acid and Incident Kidney Disease in the Community

The Relationship between Xanthine Oxidoreductase and Xanthine Oxidase Activities in Plasma and Kidney Dysfunction

Elevated Uric Acid Increases the Risk for Kidney Disease

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