Research Article
Association between uric acid and renal function in hypertensive patients: which role for systemic vascular involvement?

https://doi.org/10.1016/j.jash.2016.05.001Get rights and content

Highlights

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    Vascular changes could represent the link between serum uric acid (SUA) and renal damage.

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    Uricemia strongly correlated with estimated glomerular filtration rate, carotid intima-media thickness (cIMT), and aortic pulse wave velocity in overall study population.

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    The relationship between SUA and cIMT was similar in patients with or without chronic kidney disease.

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    The adjustment of SUA for cIMT attenuated the relationship between SUA and estimated glomerular filtration rate.

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    Vascular changes seem in part to mediate the association of SUA with renal damage.

Abstract

The role of systemic vascular involvement in mediating the association between serum uric acid (SUA) and renal function in hypertension has not been explored. Main purpose of our study was to investigate whether morphofunctional vascular changes, assessed as carotid intima-media thickness (cIMT) and aortic pulse wave velocity (aPWV), might mediate the association between SUA and renal damage. We enrolled 523 hypertensive subjects with or without chronic kidney disease and divided population into tertiles of SUA based on sex-specific cutoff values. cIMT and aPWV were higher in uppermost SUA-tertile patients when compared to those in the lowest ones (all P < .001). Uricemia strongly correlated with cIMT and aPWV at univariate analysis (P < .001) and with cIMT after adjustment for confounders (P < .001). Adjustment for cIMT attenuated the relationship between SUA and estimated glomerular filtration rate (P = .019). Systemic vascular changes seem partially to mediate the association between SUA and renal function in hypertensive patients, regardless of kidney function.

Introduction

The link between uricemia and hypertension is not completely clarified. A close association between increased serum uric acid (SUA) and high blood pressure (BP) has been demonstrated by several studies conducted in animal models as well as in humans, even if the causal connection remains to be fully elucidated.1, 2, 3, 4, 5 Furthermore, the relationship between kidney damage and SUA is controversial: hyperuricemia is associated with decreased renal function in hypertensive patients, although it is unclear whether the increased SUA is the cause or the expression of renal injury itself.3, 4, 5, 6, 7, 8

Despite all these uncertainties, several assumptions have been made about the mechanisms underlying these strong associations. Some evidences suggest that uric acid may play a causal role in the pathogenesis of endothelial dysfunction and atherosclerosis.9, 10 As matter of fact, several studies described a strong direct association between SUA and structural and functional changes of arterial vessels.11, 12, 13, 14 These alterations could somehow represent the pathophysiological bridge between SUA and kidney damage, being able to mediate at least in part this relationship.8, 9 On the other hand, it is well known that patients with chronic kidney disease (CKD) have a greater prevalence and extent of systemic vascular damage compared to subjects with normal renal function,13 and several investigations have also highlighted how vascular changes can play a role in causing kidney damage.14

Nevertheless, to the best of our knowledge, there are currently no studies that analyze the different role of systemic vascular changes, as assessed by ultrasonographic carotid intima-media thickness (cIMT) and aortic pulse wave velocity (aPWV) evaluation, in mediating the association between uricemia and kidney damage in subsets of hypertensive patients with different renal impairment.

Therefore, the purposes of our study are: (1) to investigate the relationship between SUA with both cIMT and aPWV in hypertensive subjects; (2) to assess the influence of renal function on these relationships; and (3) to study whether systemic vascular changes may mediate the association between SUA and renal function in this population.

Section snippets

Subjects

This cross-sectional study includes a total of 523 Italian hypertensive subjects. This population was selected from Caucasian hypertensive patients consecutively attending, as outpatients, our unit of Nephrology and Hypertension.

The exclusion criteria were as follows: age <30 years and >75 years; renovascular, malignant, endocrine hypertension, or hypertension associated with obstructive sleep apnea syndrome; treatment with xanthine oxidase inhibitors; severe obesity, defined as a body mass

Results

A total of 523 hypertensive patients were enrolled (mean age: 54 ± 16 years; males: 55.6%; smokers: 30.2%; CKD: 50.1%; diabetes: 26.2%). Table 1 summarizes demographic and clinical data of the overall population and of the two groups without or with CKD. SUA, aPWV, cIMT, and percentage of patients with plaques, as well as albuminuria, were significantly higher in subjects with CKD when compared to those with normal renal function, whereas eGFR was lower (all P < .001).

The percentages of

Discussion

A first important finding of our study was that, in hypertensive patients, uricemia strongly correlated with systemic vascular changes, noninvasively assessed as cIMT and aPWV, and these relationships remained significant after adjustment for multiple confounders, including age, eGFR, and albuminuria.

These results confirm the data of previous studies and add something to available evidence. A strong association between hyperuricemia and subclinical atherosclerosis was observed in generally

References (36)

  • P. Cirillo et al.

    Uric acid, the metabolic syndrome, and renal disease

    J Am Soc Nephrol

    (2006)
  • S. Sedaghat et al.

    Serum uric acid and chronic kidney disease: the role of hypertension

    PLoS One

    (2013)
  • D.B. Corry et al.

    Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system

    J Hypertens

    (2008)
  • C. Vlachopoulos et al.

    Association of serum uric acid level with aortic stiffness and arterial wave reflections in newly diagnosed, never-treated hypertension

    Am J Hypertens

    (2011)
  • G. Geraci et al.

    Relationship between carotid atherosclerosis and pulse pressure with renal hemodynamics in hypertensive patients

    Am J Hypertens

    (2016)
  • P.A. McKee et al.

    The natural history of congestive heart failure: the Framingham study

    N Engl J Med

    (1971)
  • G. Parati et al.

    Recommendations for the management of patients with obstructive sleep apnoea and hypertension

    Eur Respir J

    (2013)
  • G. Mancia et al.

    2013 ESH/ESC guidelines for the management of arterial hypertension. The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)

    J Hypertens

    (2013)

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    Conflict of interest: The authors declare no conflict of interest.

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