Physiology of Hyperuricemia and Urate-Lowering Treatments

Benn, Caroline; Dua, Pinky; Gurrell, Rachel; Loudon, Peter T.; Pike, Andrew; Storer, Richard; Vangjeli, Ciara

doi:10.3389/fmed.2018.00160

Cited by 226 publications

(196 citation statements)

References 277 publications

(294 reference statements)

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“…It has been reported that urate caused inflammatory, proliferative, and irreversible changes in glomeruli and the tubulointerstitium via various cascades, such as renal vasoconstriction, renin-angiotensin system activation, and endothelial dysfunction [30,31]. In addition, it was shown that elevated uric acid level inhibited insulin signaling and induced insulin resistance in vivo and in vitro [32], which could act together with glucose transporter in development of CKD [31]. On the other hand, it has been suggested that low to moderate alcohol consumption increased insulin sensitivity [33][34][35][36][37].…”

Section: Discussionmentioning

confidence: 99%

“…First, we did not obtain information about the types of alcohol beverages. Although it is known that beer drinking increases serum uric acid, regardless of their purine content [31], wine drinking has the possibility of not increasing serum uric acid [38]. Second, we used alcohol drinking habits and covariates at baseline as the representative of alcohol consumption.…”

Section: Discussionmentioning

confidence: 99%

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Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease

et al. 2019

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Background: Previous studies showed that higher serum uric acid levels increased the risk of chronic kidney disease (CKD), but moderate alcohol consumption decreased it. The comparative importance of serum uric acid levels and habitual alcohol consumption as risk factors for CKD remain undefined. We therefore evaluated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD. Methods: A prospective cohort study of 9,116 middle-aged nondiabetic Japanese men without CKD nor proteinuria who were not taking antihypertensive medications nor urate-lowering medications at entry. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m². We investigated the relationship of baseline serum uric acid level in combination with daily alcohol consumption to the incidence of CKD during an 11-year observation period. Daily alcohol consumption was classified into 4 groups: nondrinkers, light drinkers (0.1–23.0 g ethanol/day), moderate drinkers (23.1–46.0 g ethanol/day), and heavy drinkers (≥46.1 g ethanol/day). Cox proportional hazards models were used in multivariate analysis. Results: During the 79,361 person-years follow-up period, a total of 1,230 subjects developed CKD. In multivariate models, higher serum uric acid levels increased risk of CKD; and moderate daily alcohol consumption decreased the risk. Multiple-adjusted hazard ratios of CKD were 1.38 (95% CI 1.11–1.70), 1.58 (95% CI 1.28–1.95), 2.27 (95% CI 1.86–2.77), and 3.12 (95% CI 2.56–3.81) for quintile 2, quintile 3, quintile 4, and quintile 5 of serum uric acid levels, respectively, compared with quintile 1, and that for moderate drinkers was 0.55 (95% CI 0.46–0.66) compared with nondrinkers. In the joint analysis of alcohol consumption and serum uric acid, moderate drinkers with the lowest tertile of serum uric acid levels had the lowest risk of CKD, but nondrinkers with the highest tertile of serum uric acid levels had the highest risk of CKD. Conclusions: Serum uric acid level and daily alcohol consumption were independently associated with the risk of CKD. Nondrinkers with the highest serum uric acid level had the highest risk of CKD.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Habitual Alcohol Intake Modifies Relationship of Uric Acid to Incident Chronic Kidney Disease

et al. 2019

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“…HU is mainly associated with the following: (1) alcohol consumption; (2) a fructose rich diet; (3) excess consumption of seafood or meat; (4) diuretics; (5) some medications; and (6) angiotensin converting enzymes [8,9]. Gout is associated with precipitation of monosodium urate (MSU) crystals in joints and soft tissues [10,11]. Deposition of MSU crystals in the big toe, some joints and the ankle are associated with neutrophil infiltration, swelling and pain [12].…”

Section: Introductionmentioning

confidence: 99%

“…Deposition of MSU crystals in the big toe, some joints and the ankle are associated with neutrophil infiltration, swelling and pain [12]. The first line of gout treatment is allopurinol (ALP), a xanthine oxidase inhibitor stimulating the renal secretion and excretion of UA [11]. Other anti-inflammatory non-steroidal drugs known to inhibit cyclooxygenase activity (i.e.…”

Section: Introductionmentioning

confidence: 99%

Impact of Lesinurad and allopurinol on experimental Hyperuricemia in mice: biochemical, molecular and Immunohistochemical study

Alghamdi

Soliman

Nassan

2020

BMC Pharmacol Toxicol

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Background: Hyperuricemia is an abnormal increase in uric acid levels in the blood. It is the cause of gout that manifested by inflammatory arthritis and painful disable. Therefore, current study evaluated the potential ameliorative impact of Lesinurad and Allopurinol on the kidneys of hyperuricemic mice at the biochemical, molecular and cellular levels. Methods: Lesinurad and allopurinol alone or in combination were orally administered to hyperuricemic and control mice for seven consecutive days. Levels of uric acid and blood urea nitrogen, along with antioxidants and inflammatory cytokines (IL-1β and TNF-α) were measured in the serum. The mRNA expression of mouse urate anion transporter-1, glucose transporter 9, organic anion transporters, in renal tissues were examined using quantitative real time PCR. Simultaneously, the immunoreactivity of transforming growth factor-beta 1 was examined immunohistochemically. Results: Lesinurad and allopurinol administration resulted in significant decrease in serum levels of uric acid, blood urea nitrogen, xanthine oxidase activity, catalase, glutathione peroxidase and inflammatory cytokines (IL-1β and TNF-α) reported in hyperuricemic mice. Both partially reversed oxonate-induced alterations in renal mURAT-1, mGLUT-9, mOAT-1 and mOAT-3 expressions, as well as alterations in the immunoreactivity of TGF-β1, resulting in the increase of renal uric acid secretion and excretion. The combined administration of lesinurad and ALP restored all altered parameters in a synergistic manner, improving renal function in the hyperuricemic mouse model employed.Conclusion: This study confirmed synergistic ameliorative hypouricemic impact of both lesinurad and allopurinol in the treatment of hyperuricemia in mice at the biochemical, molecular and cellular levels.

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“…Примером такой приобретенной инфламмасомопатии является подагра. Сама гиперурикемия как предпосылка подагры может быть генетически обусловленной [6], однако аутовоспалительная подагрическая атака развивается как генетически нормальная реакция на гиперурикемию, не связанная с мутациями. В этом случае активация инфламмасомы связана с тем, что криопирин является внутриклеточным рецептором, который реагирует на различные патогены, в том числе кристаллические структуры (кристаллы мочевой кислоты, холестерина), оказавшиеся в кровотоке или интерстиции [5].…”

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