更新于：2024-11-01

HYPERURICEMIA CHRONIC

慢性高尿酸血症

更新于：2024-11-01

基本信息

别名

简介-

关联

项与慢性高尿酸血症相关的药物

Febuxostat

非布司他

靶点

作用机制

XO抑制剂

在研机构

原研机构

在研适应症

非在研适应症

最高研发阶段批准上市

首次获批国家/地区

欧盟 [+3]

首次获批日期2008-04-21

项与慢性高尿酸血症相关的临床试验

ChiCTR2000031864 / RecruitingN/AIIT

Study on the changes of hyperuricemia in medical examination population and its correlation with other physical examination indexes

开始日期2020-04-12

申办/合作机构

南方医院

CTR20132987 / Active, not recruiting

非布司他片用于治疗痛风患者高尿酸血症的有效性和安全性的多中心、随机、双盲、双模拟、平行对照临床研究

评价评价非布司他片用于治疗痛风患者高尿酸血症的有效性和安全性

开始日期2012-06-06

申办/合作机构

辰欣药业股份有限公司

100 项与慢性高尿酸血症相关的临床结果

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100 项与慢性高尿酸血症相关的转化医学

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0 项与慢性高尿酸血症相关的专利（医药）

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138

项与慢性高尿酸血症相关的文献（医药）

2024-01-01·Journal of Controlled Release

Biofunctional coacervate-based artificial protocells with membrane-like and cytoplasm-like structures for the treatment of persistent hyperuricemia

Article

作者: Zhang, Jiao ; Kong, Li ; Guo, Yuanyuan ; Wang, Mengmeng ; Lan, Hongbing ; Hu, Qian ; Tian, Yinmei ; Chen, Wei ; Li, Xiaonan ; Yu, Yulin ; Zhang, Zhiping

Coacervate droplets formed by liquid-liquid phase separation have attracted considerable attention due to their ability to enrich biomacromolecules while preserving their bioactivities. However, there are challenges to develop coacervate droplets as delivery vesicles for therapeutics resulting from the lack of physiological stability and inherent lack of membranes in coacervate droplets. Herein, polylysine-polynucleotide complex coacervate droplets with favorable physiological stability are formulated to efficiently and facilely concentrate small molecules, biomacromolecules and nanoparticles without organic solvents. To improve the biocompatibility, the PEGylated phospholipid membrane is further coated on the surface of the coacervate droplets to prepare coacervate-based artificial protocells (ArtPC) with membrane-like and cytoplasm-like structures. The ArtPC can confine the cyclic catalytic system of uricase and catalase inside to degrade uric acid and deplete the toxicity of H₂O₂. This biofunctional ArtPC effectively reduces blood uric acid levels and prevents renal injuries in mice with persistent hyperuricemia. The ArtPC-based therapy can bridge the disciplines of synthetic biology, pharmaceutics and therapeutics.

2023-08-01·Clinical rheumatology

Senescent CD4⁺CD28^null cells are increased in chronic hyperuricemia, show aberrant effector phenotypes, and are reversed after allopurinol therapy: a proof-of-concept pilot study.

Article

作者: Massó, Felipe ; Hopf-Estandía, Karen ; Del Rocío Martínez-Alvarado, María ; Ramos-Rosillo, Varna ; Páez, Araceli ; Silveira, Luis H ; Soto-Fajardo, Carina ; Espinosa-Bautista, Fernanda ; Amezcua-Guerra, Luis M ; Valdivieso-Ruiz, Melisa ; Coronel, Dania ; Pineda, Carlos ; Robledo, Sandra ; Patlán, Mariana ; Tavera-Alonso, Claudia

To characterize CD4⁺CD28^null cells in chronic hyperuricemia and investigate whether allopurinol could restore CD28 expression and the balance of T helper phenotypes. Asymptomatic individuals with chronic hyperuricemia and ultrasonographic findings evocative of urate deposition in the joints. Age- and gender-matched normouricemic individuals were also studied. Oral allopurinol at 150 mg/day for 4 weeks, followed by 300 mg/day through week 12. Color-flow cytometry on peripheral blood mononuclear cells (PBMC) with antibodies against CD4, CD28, T-bet (Th1), GATA-3 (Th2), and RORγt (Th17). Six patients (five men, median age of 53 years) and seven controls were studied. At baseline, hyperuricemic patients had more CD4⁺CD28^null/CD4⁺ cells than normouricemic subjects (36.8% vs. 6.1%; p = 0.001), with a predominance of T-bet⁺ cells (98.5% vs. 6.6%; p = 0.001) and few RORγt⁺ cells (0.7% vs. 89.4%; p = 0.014). In hyperuricemic patients, the number of CD4⁺ cells/10,000 PBMC was similar before and after allopurinol (3378 vs. 3954; p = 0.843). Conversely, CD4⁺CD28^null cells decreased from 36.8% (23.0-43.7) to 15.8% (4.7-28.1; p = 0.031). CD4⁺CD28^nullT-bet⁺ cells decreased from 98.5% (95.0-99.4) to 88.3% (75.2-98.9; p = 0.062), CD4⁺CD28^nullGATA-3⁺ cells increased from 0% (0-4.0) to 2.8% (0.1-15.6; p = 0.156), and CD4⁺CD28^nullRORγt⁺ cells increased from 0.7% (0.4-7.0) to 4.5% (1.3-28.1; p = 0.031). The CD4⁺CD28^null cell subset is abnormally expanded in chronic hyperuricemia, despite the absence of overt urate-related disease. Allopurinol may partially restore CD28 expression on CD4⁺ cells while enhancing the homeostatic balance of T helper phenotypes. ClinicalTrials.gov, number NCT04012294.

2023-02-01·American Journal of Kidney Diseases

Urate Transporter ABCG2 Function and Asymptomatic Hyperuricemia: A Retrospective Cohort Study of CKD Progression

Article

作者: Toyoda, Yu ; Ichida, Kimiyoshi ; Nakamura, Takahiro ; Yokoo, Takashi ; Nakano, Tomoko ; Nakayama, Akiyoshi ; Kawamura, Yusuke ; Sekine, Mai ; Kuriyama, Satoru ; Takada, Tappei ; Ohashi, Yuki ; Matsuo, Hirotaka

RATIONALE & OBJECTIVETreatment of asymptomatic hyperuricemia is not commonly implemented. However, it is unclear whether urate deposition that begins during asymptomatic hyperuricemia can induce nephropathy. Dysfunction of ATP-binding cassette subfamily G member 2 (ABCG2), a urate efflux transporter, leads to elevated serum uric acid concentration (SUA). We investigated the association between asymptomatic hyperuricemia and decreased estimated glomerular filtration rate (eGFR), and the impact of ABCG2 on this relationship.STUDY DESIGNRetrospective cohort study.SETTING & PARTICIPANTS1,885 Japanese adults undergoing routine health care follow-up between 2007 and 2017 who had eGFR ≥60 mL/min/1.73 m², of which 311 had asymptomatic hyperuricemia (SUA >7.0 mg/dL). Study participants were classified into 3 categories of estimated ABCG2 function (full, 75%, and ≤50% function).PREDICTORSBaseline SUA and estimated ABCG2 function.OUTCOMEChange in eGFR over time.ANALYTICAL APPROACHLinear mixed-effect models were used to analyze the relationship between asymptomatic hyperuricemia, ABCG2 function, and eGFR decline.RESULTSAsymptomatic hyperuricemia was negligibly associated with eGFR decline overall. However, among those with eGFR 60-89 mL/min/1.73 m² and ≤50% ABCG2 function, eGFR decline was associated with asymptomatic hyperuricemia (P = 0.03). ABCG2 was not associated with eGFR reductions when the SUA was <6.0 mg/dL. Among participants with SUA ≥6.0 mg/dL and eGFR 60-89 mL/min/1.73 m², ≤50% ABCG2 function was associated with approximately 1.2-fold faster eGFR decline compared with fully functional ABCG2 (P = 0.02). Among the participants with SUA ≥6.0 mg/dL and eGFR 60-89 mL/min/1.73 m², the adjusted eGFR slopes (given as mean ± standard error of the mean, in mL/min/1.73 m² per year) were -0.946 ± 0.049, -1.040 ± 0.046, and -1.148 ± 0.069 for full, 75%, and ≤50% ABCG2 function, respectively.LIMITATIONSLack of measurement of urinary urate and uremic toxins that are known to be transported by ABCG2, and no independent validation cohort.CONCLUSIONSAsymptomatic hyperuricemia was not associated with eGFR decline, except when in the presence of ≤50% ABCG2 function.PLAIN-LANGUAGE SUMMARYThe urate transporter ABCG2 is a protein that regulates serum urate concentrations; when dysfunctional, it can lead to elevated serum concentrations of this compound (ie, hyperuricemia). Although persistent hyperuricemia induces gout and kidney injury, the effects on organs during the asymptomatic phase have yet to be established. Therefore, to clarify the relationship between ABCG2, asymptomatic hyperuricemia, and kidney function, we conducted a retrospective cohort study of 1,885 healthy participants, including 311 participants with asymptomatic hyperuricemia. We found that the coexistence of asymptomatic hyperuricemia and severe ABCG2 dysfunction was associated with the age-dependent decline in kidney function. We concluded that asymptomatic hyperuricemia represents a risk factor for chronic kidney disease, at least in individuals with highly dysfunctional ABCG2. This new finding highlights the potential importance of ABCG2 in the pathogenesis of hyperuricemia-induced kidney injury.