I142 Urate-lowering therapy: what is the optimum target serum urate level?

Rheumatology ◽  
2019 ◽  
Vol 58 (Supplement_3) ◽  
Author(s):  
Fernando Perez-Ruiz
2021 ◽  
Vol 12 ◽  
Author(s):  
Zijing Ran ◽  
Xiaomei Xue ◽  
Lin Han ◽  
Robert Terkeltaub ◽  
Tony R. Merriman ◽  
...  

ObjectiveTo clarify the relationship between serum urate (SU) decrease and visceral fat area (VFA) reduction in patients with gout.MethodsWe retrospectively analyzed 237 male gout patients who had two sets of body composition and metabolic measurements within 6 months. Subjects included had all been treated with urate-lowering therapy (ULT) (febuxostat 20–80 mg/day or benzbromarone 25–50 mg/day, validated by the medical record). All patients were from the specialty gout clinic of The Affiliated Hospital of Qingdao University. The multiple linear regression model evaluated the relationship between change in SU [ΔSU, (baseline SU) – (final visit SU)] and change in VFA [ΔVFA, (baseline VFA) – (final visit VFA)].ResultsULT resulted in a mean (standard deviation) decrease in SU level (464.22 ± 110.21 μmol/L at baseline, 360.93 ± 91.66 μmol/L at the final visit, p <0.001) accompanied by a decrease in median (interquartile range) VFA [97.30 (81.15–118.55) at baseline, 90.90 (75.85–110.05) at the final visit, p < 0.001]. By multiple regression model, ΔSU was identified to be a significant determinant variable of decrease in VFA (beta, 0.302; p = 0.001).ConclusionsThe decrease in SU level is positively associated with reduced VFA. This finding provides a rationale for clinical trials to affirm whether ULT promotes loss of visceral fat in patients with gout.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 282.1-282
Author(s):  
R. Flood ◽  
C. Kirby ◽  
Y. Alammari ◽  
D. Kane ◽  
R. Mullan

Background:Emerging evidence that the joints of asymptomatic hyperuricaemic individuals contain monosodium urate (MSU) deposits and that alternative presentations of foot pain occur in hyperuricaemia suggests that preclinical phases may occur prior to a first episodic gout attack. (1) This case–control study evaluates urate deposition in hyperuricaemic individuals not fulfilling the current gout classification criteria, as well as a potential therapeutic role for urate lowering therapy (ULT).Objectives:To investigate whether ULT reduces non-episodic foot pain in patients who fail to meet ACR/EULAR 2015 gout classification criteria.Methods:Following informed consent, hyperuricaemic individuals with persistent, non-episodic foot pain (n=53) not fulfilling ACR/EULAR 2015 gout classification criteria, were compared with asymptomatic hyperuricaemic controls (n=18). Ultrasound (US) of bilateral first metatarsophalangeal (MTP) joints and features of MSU deposition including double contour (DC) sign, tophus and juxta-articular erosion were recorded. Cases only were treated with febuxostat or allopurinol daily for 6 months. Serum urate, 24-hour and 7-day visual analogue score (VAS) 0–100 mm pain scales and the Manchester Foot Pain and Disability Index (MFPDI) were recorded before treatment and after 3 and 6 months. MTP Ultrasound was repeated after a minimum of 6 months on treatment.Results:53 hyperuricaemic individuals with persistent, non-episodic foot pain not meeting the ACR/EULAR 2015 gout classification criteria were recruited. At baseline MTP US DC sign, erosion and tophus occurred in 62.5%, 20.8% and 49% of cases, respectively. No US features of gout occurred in controls. No significant difference was seen in baseline serum urate between cases (481±14 mg/dL) versus controls (437±14; p=NS). Serum urate in cases fell at 3 months (325±25; p<0.01) and 6 months (248±19; p<0.01). For cases, baseline 24-hour pain VAS (46±3.9) reduced at 3 months (32±4.1; p<0.05) and 6 months (21±5.2; p<0.05) of ULT. The 7-day pain VAS (59±3.9) decreased at 3 months (35±4.5; p<0.05) and 6 months (30±5.3; P<0.05). MFPDI (17±1.4) decreased at 3 month (13±1.8; p=<0.05) and 6 months (11±2.2; p=<0.05). When cases were grouped according to the presence (N=33) or absence (N=18) of DC sign on baseline US, no differences were observed for baseline pain scores. Following ULT however, 24-hour pain VAS were significantly lower in DC positive patients at 3 months (22±4.48 DC positive vs 42±6.14 DC negative; p<0.05) and 6 months (12.±5.4 vs 33±8.4; p<0.05). The 7-day pain VAS were significantly lower in DC positive patients at 3 months (23±4.6 vs 47±6.6; p<0.05) and MFDPI were significantly lower in DC positive patients at 3 months (10±1.9 DC positive vs 19±2.9 DC negative; p<0.05).Conclusion:These findings indicate that persistent, non-episodic foot pain in hyperuricaemia is both associated with US features of MSU deposition and is responsive to ULT. Symptomatic hyperuricaemia occurring prior to episodic gout therefore represents an earlier or alternative disease presentation. Changes to the ACR/ EULAR classification criteria to include non-episodic foot pain in the presence of US features of gout may increase the sensitivity of disease classification at an early stage, leading to improved future treatment strategies and long-term outcomes.References:[1]Stewart S, Dalbeth N, Vandal AC, Rome K. Characteristics of the first metatarsophalangeal joint in gout and asymptomatic hyperuricaemia: A cross-sectional observational study. J Foot Ankle Res. 2015;8(1):1–8.Disclosure of Interests:None declared


1989 ◽  
Vol 28 (3) ◽  
pp. 193-195 ◽  
Author(s):  
E. Lickl ◽  
G. Alth ◽  
R. Ebermann ◽  
R.H.F. Beck ◽  
K. Tuma

Rheumatology ◽  
2019 ◽  
Vol 58 (12) ◽  
pp. 2177-2180 ◽  
Author(s):  
Gurkirpal Singh ◽  
Bharathi Lingala ◽  
Alka Mithal

Abstract Objectives Several recent observations have suggested that the prevalence of gout may be increasing worldwide, but there are no recent data from the USA. We analysed the prevalence of hyperuricaemia and gout in the US population from 2007–08 to 2015–16. Methods We studied adults ⩾20 years of age from the National Health and Nutrition Examination Survey from 2007–08 to 2015–16. Persons with gout were identified from the home interview question ‘Has a doctor or other health professional ever told you that you had gout?’ Hyperuricaemia was defined as a serum urate level >0.40 mmol/l (6.8 mg/dl) (supersaturation levels at physiological temperatures and pH). Results In 2015–16, the overall prevalence of gout among US adults was 3.9%, corresponding to a total affected population of 9.2 million. Hyperuricaemia (>0.40 mmol/l or 6.8 mg/dl) was seen in 14.6% of the US population (estimated 32.5 million individuals). No significant trends were identified in the age-adjusted prevalence of gout and hyperuricaemia. Statistical comparisons between 2007–08 and 2015–16 age-adjusted rates were not significant. Conclusion While the age-adjusted prevalence of gout and hyperuricaemia has remained unchanged in the most recent decade from 2007–08 to 2015–16, the estimated total number of persons with self-reported gout has increased from 8.3 million to 9.2 million. The age-adjusted prevalence of hyperuricaemia has declined slightly, but the total number of affected individuals is virtually identical (32.5 million in 2015–16 compared with 32.1 million in 2007–08).


2013 ◽  
Vol 28 (5) ◽  
pp. 788-790 ◽  
Author(s):  
Yang Lu ◽  
Takeo Nakanishi ◽  
Miki Fukazawa ◽  
Ikumi Tamai

2017 ◽  
Vol 383 ◽  
pp. 75-78 ◽  
Author(s):  
Hirotaka Iwaki ◽  
Rina Ando ◽  
Noriyuki Miyaue ◽  
Satoshi Tada ◽  
Tomoaki Tsujii ◽  
...  

2018 ◽  
Author(s):  
Jie Lu ◽  
Ming-Shu Sun ◽  
Xin-Jiang Wu ◽  
Xuan Yuan ◽  
Zhen Liu ◽  
...  

AbstractHyperuricemia (HU) is a cause of gout. Clinical studies show a link between HU and cardiovascular disease. However, the role of soluble serum urate on atherosclerosis development remains elusive. We aimed to use a new HU mouse model (Uricase/Uox knockout (KO)) to further investigate the relationship between HU and atherosclerosis. Mouse model of induced carotid atherosclerosis was established in the novel spontaneous HU Uox-KO mouse and their wild type littermates (C57BL/6J background). Mice were implanted with a perivascular collar placement around the right carotid artery in combination with a western-type diet. To investigate urate-lowering treatment (ULT) effects on intima, the mice were gavaged daily from the age of 6 weeks with allopurinol. Human umbilical vein endothelial cells (HUVECs) were co-incubated with soluble urate, with and without probenecid, to study the mechanism of urate-related atherosclerosis. The Uox-KO mice had significantly elevated serum urate levels combined with higher blood urea nitrogen and serum creatinine. Western blot analysis showed enhanced levels of atherosclerosis inflammatory response proteins. However, there were no other risk indicators for the pathogenesis of atherosclerosis, including increased fasting glucose, altered lipid and atherosclerosis characterized cardiovascular and histological manifestations. In contrast, collar placement Uox-KO mice showed severe neointimal changes in histology staining consistent with increases in intimal area and increases in proliferating cell nuclear antigen (PCNA) - and F4/80-positive cells. Allopurinol reduced neointimal areas induced by the perivascular collar in hyperuricemic mice accompanied by decreased expression of PCNA- and F4/80-positive cells (P< 0.05). ULT alleviated atherosclerosis inflammatory response factors and reactive oxygen species intensities in both collar placement Uox-KO mice and urate-stimulated HUVECs. In vitro results using HUVECs showed ROS was induced by urate and ROS induction was abrogated using antioxidants. These data demonstrate that urate per se does not trigger atherosclerosis intima lesions in mice. Urate worsens carotid neointimal lesions induced by the perivascular collar and urate-lowering therapy partially abrogates the effects. The current study warrants the further human based study on the possible benefits of urate-lowering therapy in atherosclerosis patients with HU.Summary statementWe generated a carotid collar placement atherosclerosis model in the novel spontaneous HU Uox-KO mouse and demonstrate that urate plays a contributing rather than a causal role in the carotid neointimal lesions, while urate-lowering treatment may bring additional benefits in this HU mouse model.


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