RESUMO
Hyperuricemia, a prevalent metabolic disorder, poses a susceptibility to various complications. The conventional pharmacotherapeutic approaches for hyperuricemia often entail notable adverse effects, posing substantial clinical challenges. Hence, the imperative lies in the development of novel, safe and effective strategies for preventing and treating hyperuricemia. Here, we developed a probiotic Escherichia coli Nissle 1917 strain, designated as YES301, which contains a rationally designed xanthine importer XanQ, enabling efficient uptake of xanthine and hypoxanthine, consequently leading to reduced serum uric acid concentrations and amelioration of renal impairments in a murine model of hyperuricemia. Importantly, YES301 exhibited a therapeutic efficacy comparable to allopurinol, a conventional uric acid-lowering agent, and manifesting fewer adverse effects and enhanced biosafety. These findings highlight the promising potential of engineered probiotics in the management of hyperuricemia through reducing intestinal purine levels.
Assuntos
Escherichia coli , Hiperuricemia , Probióticos , Xantina , Hiperuricemia/tratamento farmacológico , Hiperuricemia/terapia , Hiperuricemia/metabolismo , Probióticos/administração & dosagem , Probióticos/uso terapêutico , Animais , Camundongos , Xantina/metabolismo , Escherichia coli/metabolismo , Escherichia coli/genética , Ácido Úrico/metabolismo , Ácido Úrico/sangue , Modelos Animais de Doenças , Masculino , Humanos , Camundongos Endogâmicos C57BL , Hipoxantina/metabolismo , Alopurinol/uso terapêuticoRESUMO
OBJECTIVES: Platelet-rich plasma treatment delays the need for total knee replacement in patients with knee osteoarthritis. However, its use and preparation remain controversial. The aim of this study was to investigate the relationship between anticoagulant use in the preparation of platelet-rich plasma and post-treatment pain in patients with knee osteoarthritis. Additionally, we explored the efficacy of platelet-rich plasma over medium- and long-term follow-up periods and identified other factors that may affect treatment outcomes. METHODS: In this retrospective study, 225 patients with knee osteoarthritis, who underwent knee platelet-rich plasma treatment from June 2021 to January 2022, were examined at three study centres. Patients were categorised, based on the type and amount of anticoagulant used during platelet-rich plasma preparation, into 4% sodium citrate (SC) 0.6 mL, 4% SC 1 mL, 4% SC 2 mL, heparin 0.1 mL, and heparin 0.2 mL groups. We analysed the patients' basic information, pain after treatment, and inflammatory markers (i.e., interleukin 6, tumour necrosis factor-α, and hypersensitive C-reactive protein) in the joint fluid via enzyme-linked immunosorbent assay and joint fluid crystallisation. Additionally, we assessed the patients' Western Ontario and McMaster University scores and minimal clinically significant differences after treatment. RESULTS: Patients in the 4% SC 0.6 mL and heparin 0.1 mL groups experienced less pain after platelet-rich plasma treatment than did patients in the high-dose anticoagulant group. The joint fluid of patients with pain in these groups had lower levels of inflammatory markers. Patients treated with SC had slightly better medium- and long-term therapeutic outcomes than did patients treated with heparin. Patients with poorly controlled hyperuricemia also experienced pain after platelet-rich plasma treatment. CONCLUSIONS: The results suggest that platelet-rich plasma prepared using high-dose anticoagulants or administered to patients with poorly controlled hyperuricaemia may lead to moderate-to-severe knee pain and joint effusion after joint puncture therapy. Platelet-rich plasma had a therapeutic effect on knee osteoarthritis; however, its efficacy gradually decreased over time. SC anticoagulant is more suitable for platelet-rich plasma preparation than is heparin. Further studies are needed to understand the safety and the various factors influencing platelet-rich plasma therapy.
Assuntos
Anticoagulantes , Hiperuricemia , Osteoartrite do Joelho , Plasma Rico em Plaquetas , Humanos , Estudos Retrospectivos , Masculino , Feminino , Osteoartrite do Joelho/terapia , Anticoagulantes/administração & dosagem , Idoso , Hiperuricemia/terapia , Hiperuricemia/complicações , Pessoa de Meia-Idade , Artralgia/etiologia , Artralgia/terapia , Artralgia/diagnóstico , Heparina/administração & dosagem , Citrato de Sódio/administração & dosagem , Injeções Intra-Articulares , Medição da DorRESUMO
Hyperuricaemia (HUA) is an abnormally high concentration of serum urate caused by either an excess of uric acid production or decreased excretion capacity in the body. Serum urate concentration forms sodium salts that deposit in the soft tissues of the joints, ultimately leading to gout. Additionally, HUA is strongly associated with several acute and chronic illnesses. In various clinical guidelines and practices, xanthine oxidase inhibitors, such as allopurinol and febuxostat, are commonly used as the initial medication for treating HUA. However, extended usage of urate-lowering drugs may have risks, including cardiovascular thrombotic events and hepatic impairment. Implementing a scientifically informed fitness diet in conjunction with appropriate exercise may decrease HUA. Unfortunately, there is currently a shortfall in exercise intervention trials for individuals suffering from HUA. Most of the previous evidence suggesting that exercise improves serum urate levels comes from intervention trials in other populations, and serum urate is only one of the outcomes observed. This opinion article analyses the causes of HUA, offers dietary and exercise guidance with the aim of furnishing a point of reference for individuals with HUA or fitness enthusiasts.
Assuntos
Terapia por Exercício , Exercício Físico , Gota , Hiperuricemia , Ácido Úrico , Humanos , Alopurinol/efeitos adversos , Alopurinol/uso terapêutico , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Febuxostat/efeitos adversos , Febuxostat/uso terapêutico , Gota/sangue , Gota/etiologia , Gota/terapia , Supressores da Gota/efeitos adversos , Supressores da Gota/uso terapêutico , Hiperuricemia/sangue , Hiperuricemia/complicações , Hiperuricemia/terapia , Ácido Úrico/sangue , Ácido Úrico/metabolismoRESUMO
Hyperuricemia (HUA) is a metabolic syndrome caused by abnormal purine metabolism. Although recent studies have noted a relationship between the gut microbiota and gout, whether the microbiota could ameliorate HUA-associated systemic purine metabolism remains unclear. In this study, we constructed a novel model of HUA in geese and investigated the mechanism by which Lactobacillus rhamnosus GG (LGG) could have beneficial effects on HUA. The administration of antibiotics and fecal microbiota transplantation (FMT) experiments were used in this HUA goose model. The effects of LGG and its metabolites on HUA were evaluated in vivo and in vitro. Heterogeneous expression and gene knockout of LGG revealed the mechanism of LGG. Multi-omics analysis revealed that the Lactobacillus genus is associated with changes in purine metabolism in HUA. This study showed that LGG and its metabolites could alleviate HUA through the gut-liver-kidney axis. Whole-genome analysis, heterogeneous expression, and gene knockout of LGG enzymes ABC-type multidrug transport system (ABCT), inosine-uridine nucleoside N-ribohydrolase (iunH), and xanthine permease (pbuX) demonstrated the function of nucleoside degradation in LGG. Multi-omics and a correlation analysis in HUA patients and this goose model revealed that a serum proline deficiency, as well as changes in Collinsella and Lactobacillus, may be associated with the occurrence of HUA. Our findings demonstrated the potential of a goose model of diet-induced HUA, and LGG and proline could be promising therapies for HUA.
Assuntos
Hiperuricemia , Lacticaseibacillus rhamnosus , Humanos , Hiperuricemia/terapia , Nucleosídeos , Lactobacillus , Prolina , PurinasRESUMO
Gout is a disease caused by the chronic deposition of monosodium urate crystals. Its clinical presentation as an acute, self-limiting arthritis and the belief that it is a banal, self-inflicted disease have led to its poor management. Despite advances in the knowledge of the disease and the simplicity of its management, no more than 30% of patients are well treated. In Spain, the prevalence of gout is 2.5% and its incidence is increasing. In the following article we will review the pathogenesis of gout and hyperuricaemia, highlighting the greater weight of genetics and renal function over diet. We will look at the consequences of crystal deposition. Gout, in addition to its joint presentation and renal involvement, has been shown to be an independent cardiovascular risk factor. Hypouricemic therapy is the most important treatment, as it is the one that dissolves the crystals and cures the disease. This requires the sustained achievement of uricemia levels below 6mg/dl. We will also review preventive and flares treatment, as well as the role of patient education in terms of both lifestyle and dietary habits and adherence to pharmacological treatment.
Assuntos
Gota , Hiperuricemia , Humanos , Gota/terapia , Gota/diagnóstico , Hiperuricemia/terapia , Hiperuricemia/diagnóstico , Hiperuricemia/etiologia , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Espanha , Educação de Pacientes como Assunto , Estilo de Vida , Supressores da Gota/uso terapêutico , Prevalência , Dieta , Fatores de Risco , Incidência , Adesão à Medicação , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/terapiaRESUMO
BACKGROUND: Although the correlation between hyperuricemia and cardiovascular disease (CVD) is well known, there have been limited data regarding the impact of hyperuricemia on long-term clinical outcomes in patients with peripheral arterial disease (PAD) after percutaneous transluminal angioplasty (PTA). METHODS: A total of 718 patients who underwent PTA for PAD were enrolled. The patients were divided into the hyperuricemia group (N = 168) and the normal group (N = 550). Hyperuricemia was defined as a uric acid level ≥ 7.0 mg/dL in men, and ≥ 6.5 mg/dL in women. The primary endpoint was major adverse cerebral and cardiovascular event (MACCE), including death, myocardial infarction (MI), any coronary revascularization, and stroke, up to 5 years. The secondary endpoint was major adverse limb event (MALE), including any repeated PTA, and target extremity surgery (TES). Inverse probability weighting (IPTW) analysis, derived from the logistic regression model, was performed to adjust potential confounders. RESULTS: After IPTW matching analysis, compared to the normal group, the hyperuricemia group was not associated with increased MACCE but was associated with an increased incidence of MI (2.6 % vs. 0.5 %, p = 0.001), and coronary revascularization (6.7 % vs. 3.9 %, p = 0.018). Also, the hyperuricemia group was associated with a higher incidence of MALE (45.3 % vs. 28.9 %, p < 0.001), including target extremity revascularization (TER; 25.1 % vs. 15.9 %, p < 0.001), non-TER (11.5 % vs. 5.6 %, p < 0.001), and TES (22.8 % vs. 16.2 %, p = 0.002). CONCLUSIONS: In the present study, hyperuricemia was associated with worse clinical outcomes in PAD patients following PTA during 5-year clinical follow-up. Further investigations should be made regarding the clinical benefit of controlling hyperuricemia on clinical outcomes.
Assuntos
Hiperuricemia , Doença Arterial Periférica , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/sangue , Hiperuricemia/terapia , Hiperuricemia/mortalidade , Masculino , Feminino , Idoso , Resultado do Tratamento , Doença Arterial Periférica/terapia , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/diagnóstico , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Estudos Retrospectivos , Biomarcadores/sangue , Ácido Úrico/sangue , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/terapia , Infarto do Miocárdio/diagnóstico , IncidênciaAssuntos
Doenças Cardiovasculares , Hiperuricemia , Humanos , Hiperuricemia/complicações , Hiperuricemia/diagnóstico , Hiperuricemia/terapia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Consenso , Fatores de Risco , Fatores de Risco de Doenças CardíacasRESUMO
Background: Hyperuricemia is associated with several risk factors for mortality and severe coronavirus disease 2019 (COVID-19) manifestations.Objective: The objective of this research was to examine whether hyperuricemia is a risk factor for mortality and other adverse outcomes in patients hospitalized for COVID-19.Design: This is a retrospective review of patients hospitalized for COVID-19 between March 15 and November 30, 2020, with available uric acid (UA) levels.Results: Among 1566 patients who were hospitalized during the study period, 222 patients had an available UA level. The mean age ± standard deviation (SD) was 56.5 ± 19.5 years. The mean ± SD for UA (mg/dL) among the total cohort was 5.65 ± 2.18, and 21.2% of the total study population had hyperuricemia (UA > 7 mg/dL) on admission. The mortality rate was 14.4%, and mortality was associated with higher UA levels on admission (6.9 ± 2.6 mg/dL vs. 5.5 ± 2 mg/dL in patients who survived, P < 0.05). Patients who needed intensive oxygen support (high-flow nasal cannula or mechanical ventilation) and those who required longer-than-average hospitalization (> 7 days) had more hyperuricemia (intensive oxygen support: 30% vs. 18%, P = 0.07; long hospitalization 29% vs. 16.2%, P < 0.05).Conclusion: Our findings show that high UA levels are associated with adverse outcomes in patients hospitalized for COVID-19. We suggest evaluating hyperuricemia as a marker that integrates and reflects both poor prognostic baseline characteristics and acute components such as inflammatory state, hypovolemic state, and renal failure.
Assuntos
COVID-19 , Hiperuricemia , Humanos , Hiperuricemia/complicações , Hiperuricemia/terapia , COVID-19/complicações , COVID-19/terapia , Prognóstico , Fatores de Risco , Hospitalização , Ácido ÚricoRESUMO
Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.
Assuntos
Hiperuricemia , Proteoglicanas , Reishi , Animais , Humanos , Camundongos , Adenosina/farmacologia , Adenosina Desaminase/metabolismo , Hiperuricemia/terapia , Rim/efeitos dos fármacos , Transportadores de Ânions Orgânicos/metabolismo , Reishi/química , Proteoglicanas/isolamento & purificação , Proteoglicanas/farmacologia , Proteoglicanas/uso terapêuticoRESUMO
In this study, we determined the purine contents in milk and soymilk, as protein-rich drinks, and in enteral nutritional supplements employed to ameliorate protein malnutrition in the elderly. Milk consumption is known to lower serum uric acid levels and to promote uric acid excretion. However, discrepant results have been reported regarding the effect of soymilk on serum uric acid levels. The purpose of this study was to quantify and compare the total purine contents and the contents of individual purines and pyrimidines by molecular type (nucleotides, nucleosides, and bases).
Assuntos
Gota , Hiperuricemia , Humanos , Idoso , Animais , Hiperuricemia/terapia , Ácido Úrico , Leite/química , Purinas/metabolismoRESUMO
Gout is the most common inflammatory arthritis in men with a rising incidence worldwide. It is a metabolic disease caused by hyperuricemia. Common causes of hyperuricemia, in addition to hereditary reduced renal excretion of urate, include purine over-nutrition, aging, comorbidities and associated medications, some of which increase serum urate levels. The first gout flare represents the signal for deposited urate crystals. If hyperuricemia remains untreated, crystal deposition proceeds and can cause recurrent gout flares, joint destruction and tophi. There is evidence that silent inflammation is ongoing even during asymptomatic stages. Gout patients often exhibit other metabolic, renal and cardiovascular co-morbidities and have higher (cardiovascular) mortality. Therefore, guidelines call for consequent urate lowering strategies to bring serum urate levels to a target at least below 360⯵mol/l. The following article summarizes the recent state of knowledge regarding the diagnosis and therapy of gout.
Assuntos
Gota , Hiperuricemia , Gota/diagnóstico , Gota/terapia , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/terapia , Masculino , Exacerbação dos Sintomas , Ácido ÚricoRESUMO
Hyperuricemia is often encountered as glomerular filtration rate decreased. It is associated with a more rapid decline of the renal function, but causality has not been demonstrated. Recent studies showed that treatment of hyperuricemia did not affect the progression in chronic kidney disease (CKD) patients. Thus, treatment with hypouricemic drugs of patients suffering of CKD and displaying asymptomatic hyperuricemia is not recommended. However, patients with CKD present often with acute flairs of gout, which might be difficult to treat. Therapeutic options are discussed in this article.
Une hyperuricémie apparaît précocement en cas de diminution de la filtration glomérulaire et de maladie rénale chronique. Elle est associée à un déclin plus rapide de la fonction rénale, mais un lien de causalité n'a pas été démontré. Plusieurs études récentes n'ont pas montré d'effet bénéfique d'un traitement hypo-uricémiant sur l'évolution de la fonction rénale. Ainsi, en cas d'hyper uricémie asymptomatique chez un patient souffrant de maladie rénale chronique, un traitement hypo-uricémiant n'est pas indiqué. Cependant, les patients souffrant de maladie rénale chronique font plus fréquemment des crises de goutte, et leur prise en charge est complexe car la maladie est à la fois plus résistante au traitement et les options thérapeutiques sont limitées. Celles-ci sont revues dans cet article.
Assuntos
Gota , Hiperuricemia , Insuficiência Renal Crônica , Gota/complicações , Gota/terapia , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/complicações , Hiperuricemia/terapia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Ácido Úrico/uso terapêuticoRESUMO
Urate oxidase is a promising biological medicine for hyperuricemia treatment, but immunogenicity obstructs the development of its clinical application. The recombinant porcine-human chimeric uricase mutant named dHU-wPU is a humanized chimeric uricase based on wild porcine uricase (wPU), which can effectively reduce the limitation of potential immunogenicity with a high homology (92.76%) to deduced human uricase (dHU). Unfortunately, the insoluble expression form of dHU-wPU in E. coli increases the difficulty of production. In this study, we described a more convenient method to efficiently obtain recombinant dHU-wPU protein from E. coli. Combination small ubiquitin-related modifier protein (SUMO) and maltose-binding protein (MBP) was employed to achieve the soluble expression of dHU-wPU. MBP-SUMO-dHU-wPU fusion protein was not only overexpressed in a soluble form, but also showed high purification and cleavage efficiency. Subsequently, we optimized the culture conditions of shake flasks and expanded the production of MBP-SUMO-dHU-wPU fusion protein in a 5 L bioreactor. Finally, about 15 mg of recombinant dHU-wPU was obtained from 1 L M9 fermentation culture by using two-step affinity chromatography, with a SDS-PAGE purity over 90%. In vitro activity analysis showed that dHU-wPU had better ability to catalyze uric acid than wPU.
Assuntos
Clonagem Molecular/métodos , Proteínas Ligantes de Maltose/genética , Proteínas Recombinantes de Fusão/genética , Proteína SUMO-1/genética , Urato Oxidase/genética , Animais , Reatores Biológicos , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Humanos , Hiperuricemia/genética , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Hiperuricemia/terapia , Proteínas Ligantes de Maltose/metabolismo , Mutação , Plasmídeos/química , Plasmídeos/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteína SUMO-1/metabolismo , Solubilidade , Suínos , Urato Oxidase/metabolismo , Ácido Úrico/metabolismoRESUMO
Background: Hyperuricemia (HUA) is a metabolic disease by purine metabolism disorders. It is a risk factor for many chronic diseases, including diabetes, hypertension, and heart disease. Studies have shown that exercise can effectively reduce serum uric acid (SUA), but the optimal exercise dose, intensity, and mode of exercise for improving HUA have not been verified in clinical studies. Therefore, this study aims to explore the effect of different exercise intensities in improving SUA of patients with HUA. Methods and Analysis: A randomized, single-blind, parallel controlled trial will be conducted in this study. 186 HUA patients who meet the inclusion criteria will be randomly divided into a 1:1:1 ratio (1): control group (2), low-intensity exercise group (brisk walking, 57-63% maximum heart rate, 150 min/week, 12 months), and (3) moderate-intensity exercise group (jogging, 64-76% maximum heart rate, 150 min/week, 12 months). The three groups of subjects will receive the same health education and prohibition of high-purine diet during the intervention period. The primary outcomes will be SUA concentration, SUA concentration change (mg/dL), SUA change rate (%), and the proportion of HUA patients. Secondary outcomes will include anthropometric parameters (body weight, waist circumference, hip circumference, BMI); physiological indicators (blood pressure, grip, vital capacity, maximum oxygen); biochemical indicators (blood lipid, blood sugar, liver enzyme, creatinine, and blood urea nitrogen). Each group of patients will go through an assessment at baseline, 3rd, 6th, and 12th months. Discussion: This study will evaluate the effect of 12-month low-intensity exercise and moderate-intensity exercise on HUA patients. We hypothesize that both low-intensity and moderate-intensity exercise would improve HUA as compared with no-exercise control, and that moderate-intensity exercise would be more effective than low-intensity exercise in improving HUA. These results can provide a basis for the current physical activity guidelines for HUA's healthy lifestyle management. Ethics and Dissemination: This study has been approved by the Ethical Review Committee of the Shanghai University of Sport (approval number: 102772020RT005). Informed consent will be obtained from all participants or their guardians. The authors intend to submit the study findings to peer-reviewed journals or academic conferences to be published. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier ChiCTR2100042643.
Assuntos
Hiperuricemia/terapia , China/epidemiologia , Exercício Físico , Feminino , Seguimentos , Humanos , Hiperuricemia/epidemiologia , Hiperuricemia/patologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-CegoRESUMO
BACKGROUND: Hyperuricemia is found to be associated with the development and progression of gout, chronic kidney disease, cardiovascular diseases and several others. However, consistent recommendation in the management of hyperuricemia among physicians in India is absent. This study was done to assess the knowledge, attitude, practice (KAP) and barriers in the management of hyperuricemia among physicians in India. METHODS: A cross-sectional study using a telephonically-administered questionnaire was distributed to 350 physicians treating hyperuricemia patients with co-morbidities like hypertension, diabetes mellitus, metabolic syndrome etc. The questionnaire included 25 questions on qualitative and quantitative aspects. Descriptive statistics were used for demographic characteristics. Inferential statistics (binary logistic regression) was used to identify the relationship between knowledge scores across different physician factors. RESULTS: A total of 350 responses were obtained with a response rate of 100%. Majority of the physicians (90%) were male and 10% were female with median age of 45.5 ± 12.2 years. Mean scores for knowledge and attitude were 7.4 ± 2.35 and 12.1 ± 1.6, respectively. 66.1% (230) of physicians had adequate knowledge score, while the remaining 33.9% (118) had inadequate score. Irrespective of comorbidity status, no change in the attitude of physicians towards management of hyperuricemia was found. CONCLUSION: This study demonstrated that the majority of physicians demonstrated adequate level of knowledge, positive/favourable attitude and reported optimal treatment practices for the management of hyperuricemia while exhibiting a few perceived barriers. Nevertheless, facilitating widespread physician awareness about the benefits of optimal management of hyperuricemia is warranted.
Assuntos
Hiperuricemia , Médicos , Adulto , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hiperuricemia/epidemiologia , Hiperuricemia/terapia , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.
Assuntos
Doenças Cardiovasculares/etiologia , Suscetibilidade a Doenças , Hiperuricemia/complicações , Hiperuricemia/metabolismo , Síndrome Metabólica/etiologia , Insuficiência Renal Crônica/etiologia , Animais , Biomarcadores , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/terapia , Gerenciamento Clínico , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/terapia , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Síndrome Metabólica/terapia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/terapia , Índice de Gravidade de DoençaRESUMO
Urate homeostasis in humans is a complex and highly heritable process that involves i.e., metabolic urate biosynthesis, renal urate reabsorption, as well as renal and extrarenal urate excretion. Importantly, disturbances in urate excretion are a common cause of hyperuricemia and gout. The majority of urate is eliminated by glomerular filtration in the kidney followed by an, as yet, not fully elucidated interplay of multiple transporters involved in the reabsorption or excretion of urate in the succeeding segments of the nephron. In this context, genome-wide association studies and subsequent functional analyses have identified the ATP-binding cassette (ABC) transporter ABCG2 as an important urate transporter and have highlighted the role of single nucleotide polymorphisms (SNPs) in the pathogenesis of reduced cellular urate efflux, hyperuricemia, and early-onset gout. Recent publications also suggest that ABCG2 is particularly involved in intestinal urate elimination and thus may represent an interesting new target for pharmacotherapeutic intervention in hyperuricemia and gout. In this review, we specifically address the involvement of ABCG2 in renal and extrarenal urate elimination. In addition, we will shed light on newly identified polymorphisms in ABCG2 associated with early-onset gout.
Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Suscetibilidade a Doenças , Gota/etiologia , Hiperuricemia/etiologia , Proteínas de Neoplasias/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Idade de Início , Alelos , Animais , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Genótipo , Gota/diagnóstico , Gota/metabolismo , Gota/terapia , Humanos , Hiperuricemia/diagnóstico , Hiperuricemia/metabolismo , Hiperuricemia/terapia , Proteínas de Neoplasias/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Gout is a metabolically-related joint disease, characterized by recurrent episodic arthritis. The recent epidemiological study suggests that the incidence of hyperuricemia and gout in many countries has risen especially in recent decades. A possible explanation may be a decreased physical activity level and changes in eating habits. The patients lifestyle is one of the key factors contributing to the development of hyperuricemia. For patients, an important part of therapy is non-pharmacological treatment through changes in lifestyle factors such as dietary measures, weight control, and adequate hydration and exercise. Lifestyle changes can lead to beneficial health changes in patients. The relationships between serum uric acid levels, hyperuricemia, obesity, and metabolic syndrome are well established. Higher serum uric acid concentration positively correlates with body mass index (BMI) and metabolic syndrome. The reduction of BMI may lead to improved hyperuricemia in patients. Other important changes include stopping alcohol consumption, reducing the intake of sweetened beverages, increasing the intake of dairy products, no eating organ meats, sea fish, sausages. Proper hydration is also an important part of the treatment.
Assuntos
Gota , Hiperuricemia , Animais , Laticínios , Dieta , Gota/epidemiologia , Gota/terapia , Humanos , Hiperuricemia/epidemiologia , Hiperuricemia/terapia , Fatores de Risco , Ácido ÚricoRESUMO
Hyperuricaemia (HU) caused by disorders of purine metabolism is a metabolic disease. A number of epidemiological reports have confirmed that HU is correlated with multiple disorders, such as chronic kidney diseases, cardiovascular disease and gout. Recent studies showed that the expression and functional changes of uric acid transporters, including URAT1, GLUT9 and ABCG2, were associated with HU. Moreover, a large number of genome-wide association studies have shown that these transporters' dysfunction leads to HU. In this review, we describe the recent progress of aetiology and related transporters of HU, and we also summarise the common co-morbidities possible mechanisms, as well as the potential pharmacological and non-pharmacological treatment methods for HU, aiming to provide new ideas for the treatment of HU.
Assuntos
Gota/terapia , Hiperuricemia/genética , Hiperuricemia/terapia , Doenças Cardiovasculares/sangue , Comorbidade , Estudo de Associação Genômica Ampla , Gota/sangue , Gota/patologia , Humanos , Hiperuricemia/metabolismo , Hiperuricemia/patologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/terapia , Ácido Úrico/sangueRESUMO
BACKGROUND: The Reporting Items for Practice Guidelines in Healthcare (RIGHT) checklist was used to assess the reporting quality of 2009-2019 clinical practice guidelines (CPGs) regarding gout and hyperuricemia, aimed to improve the reporting quality of future guidelines. METHODS: We searched PubMed, the Chinese Biomedical Literature database, the Wanfang Database, and the China National Knowledge Infrastructure from January 2009 to June 2019 for guidelines regarding gout and hyperuricemia. We also searched the websites of guideline development organizations (the Guidelines International Network, the National Institute for Health and Clinical Excellence, the American College of Rheumatology, and the European League Against Rheumatism (EULAR)). Furthermore, supplementary guidelines reported in included articles were systematically searched, as well as Google Scholar. RESULTS: Seventeen guidelines were included, of which one was in Chinese and 16 were in English. The mean reporting rate of the 35 items specified was 14.9 (42.5%); only five CPGs (29.4%) had a reporting rate >50%. Of the 35 items, three were very frequently reported. The reporting proportion of the seven domains (basic information, background, evidence, recommendations, review and quality assurance, funding and declaration and management of interests, and other information) were 64.7%, 36.8%, 50.6%, 42.9%, 8.82%, 33.8%, and 31.4%, respectively. CONCLUSION: The reporting quality of the present guidelines for gout and hyperuricemia is relatively poor. We suggest that the RIGHT reporting checklist should be used by CPG developers to ensure higher reporting quality of future guidelines.