Gender-related differences in serum uric acid in treated hypertensive patients from central and east European countries

Redon, P.; Maloberti, Alessandro; Facchetti, Rita; Redón, Josep; Lurbe, Empar; Bombelli, Michele; Mancia, Giuseppe

doi:10.1097/hjh.0000000000001908

Cited by 47 publications

(37 citation statements)

References 38 publications

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“…HUA also increases the overall risk for hypertension for both sexes, but once again females with HUA are more likely to develop hypertension than HUA males compared to non-HUA controls [51,54,57]. Finally, females have a higher incidence of type 2 diabetes mellitus than males [52], yet HUA females are even more likely to develop diabetes than HUA males [54], further emphasizing that an increase in SUA can be more detrimental to females than males. However, since HUA is only one of several pathologies to affect people later in life, the role of UA in the biogenesis of the underlying pathology is difficult to tease out, demonstrating the critical need for additional studies.…”

Section: Urate As a Risk Factor In Diseasementioning

confidence: 94%

“…As kidney function declines, SUA levels tend to increase, and increases have been reported to be associated with all-cause and cardiovascular mortality in a dose-dependent manner. Thus, as UA levels increase, so does the risk of developing other conditions, including CKD, hypertension, and diabetes mellitus [50][51][52][53][54][55], especially in women [12,56]. Table 1 summarizes data that compares the comorbidities of individuals who have low SUA with individuals who have high SUA, stratified by sex.…”

Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

“…HUA increases the risk of developing CKD for both men and women and increases the likelihood of progression to ESRD in both sexes, yet this risk is much higher in HUA females than HUA males [50]. Similarly, the incidence of CKD increases two-fold to six-fold higher in HUA females than HUA males [51,52], demonstrating that once females have lost the benefit of low SUA, renal health is more likely to decline. Males and females with both HUA and CKD had a higher incidence of left ventricular hypertrophy and hypertension, however, this association was only significant in females [53].…”

Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

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Sex Differences in Urate Handling

Kuhns

Woodward

2020

IJMS

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Hyperuricemia, or elevated serum urate, causes urate kidney stones and gout and also increases the incidence of many other conditions including renal disease, cardiovascular disease, and metabolic syndrome. As we gain mechanistic insight into how urate contributes to human disease, a clear sex difference has emerged in the physiological regulation of urate homeostasis. This review summarizes our current understanding of urate as a disease risk factor and how being of the female sex appears protective. Further, we review the mechanisms of renal handling of urate and the significant contributions from powerful genome-wide association studies of serum urate. We also explore the role of sex in the regulation of specific renal urate transporters and the power of new animal models of hyperuricemia to inform on the role of sex and hyperuricemia in disease pathogenesis. Finally, we advocate the use of sex differences in urate handling as a potent tool in gaining a further understanding of physiological regulation of urate homeostasis and for presenting new avenues for treating the constellation of urate related pathologies.

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Section: Urate As a Risk Factor In Diseasementioning

confidence: 94%

Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

Section: Urate As a Risk Factor In Diseasementioning

confidence: 99%

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Sex Differences in Urate Handling

Kuhns

Woodward

2020

IJMS

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“…This inverse correlation is stronger in female subjects; male subjects only show a trend. In a recent study in treated hypertensive patients, 25% of which have hyperuricemia, rate of uncontrolled BP is higher in men with hyperucicermia versus normouricemia whereas it is similar in normouricemic and hyperuricemic women [ 46 ]. Gender difference has also been demonstrated in another recent study, in which urate is positively associated with pulse pressure (difference between SBP and DBP) only in women not in men [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease

et al. 2018

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BackgroundEpidemiological, laboratory and clinical studies have established an association between elevated urate and high blood pressure (BP). However, the inference of causality remains controversial. A naturally occurring antioxidant, urate may also be neuroprotective, and urate-elevating treatment with its precursor inosine is currently under clinical development as a potential disease-modifying strategy for Parkinson's disease (PD).MethodsOur study takes advantage of a recently completed phase II trial evaluating oral inosine in de novo non-disabling early PD with no major cardiovascular and nephrological conditions, and of three lines of genetically engineered mice: urate oxidase (UOx) global knockout (gKO), conditional KO (cKO), and transgenic (Tg) mice with markedly elevated, mildly elevated, and substantially reduced serum urate, respectively, to systematically investigate effects of urate-modifying manipulation on BP.FindingsAmong clinical trial participants, change in serum urate but not changes in systolic, diastolic and orthostatic BP differed by treatment group. There was no positive correlation between urate elevations and changes in systolic, diastolic and orthostatic BP ((p = .05 (in inverse direction), 0.30 and 0.63, respectively)). Between UOx gKO, cKO, or Tg mice and their respective wildtype littermates there were no significant differences in systolic or diastolic BP or in their responses to BP-regulating interventions.InterpretationOur complementary preclinical and human studies of urate modulation in animal models and in generally healthy early PD do not support a hypertensive effect of urate elevation or an association between urate and BP.FundU.S. Department of Defense, RJG Foundation, Michael J. Fox Foundation LEAPS program, National Institutes of Health, American Federation for Aging Research, Parkinson's Disease Foundation Advancing Parkinson's Therapies initiative.

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“…Hyperuricemia is a disease associated with lifestyle habits, and the increasing frequency of hyperuricemia and gout is most likely caused by westernized lifestyles and environments [ 1 ]. Hyperuricemia can be a risk factor not only for gouty arthritis and kidneys and ureteric stones, but also for cardiovascular and chronic kidney diseases [ 2 , 3 ]. Therefore, as an appropriate intervention, hyperuricemia should be tackled at an early stage [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Osthol Isolated from Cnidium monnieri Fruit on Urate Transporter 1

et al. 2018

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(1) Background: Crude drugs used in traditional Japanese Kampo medicine or folk medicine are major sources of new chemical entities for drug discovery. We screened the inhibitory potential of these crude drugs against urate transporter 1 (URAT1) to discover new drugs for hyperuricemia. (2) Methods: We prepared the MeOH extracts of 107 different crude drugs, and screened their inhibitory effects on URAT1 by measuring the uptake of uric acid by HEK293/PDZK1 cells transiently transfected with URAT1. (3) Results: We found that the extract of the dried mature fruit of Cnidium monnieri inhibited urate uptake via URAT1. We isolated and identified osthol as the active ingredient from this extract. Osthol noncompetitively inhibited URAT1 with an IC50 of 78.8 µM. We evaluated the effects of other coumarins and found that the prenyl group, which binds at the 8-position of coumarins, plays an important role in the inhibition of URAT1. (4) Conclusions: Cnidium monnieri fruit may be useful for the treatment of hyperuricemia or gout in traditional medicine, and its active ingredient, osthol, is expected to be a leading compound for the development of new drugs for hyperuricemia.

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Gender-related differences in serum uric acid in treated hypertensive patients from central and east European countries

Cited by 47 publications

References 38 publications

Sex Differences in Urate Handling

Sex Differences in Urate Handling

Dissociation between urate and blood pressure in mice and in people with early Parkinson's disease

Effects of Osthol Isolated from Cnidium monnieri Fruit on Urate Transporter 1

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