高尿酸血症与肠道菌群的相关性

最新研究数据表明,我国人群中高尿酸血症患病率已高达13%,且有不断上升及年轻化趋势。尿酸是人体嘌呤代谢的终产物,嘌呤是核酸的氧化分解代谢产物。体内产生的嘌呤在肝脏中再次氧化为(2,6,8-三氧嘌呤),即尿酸,其中2/3尿酸经肾脏随尿液排出体外,1/3通过粪便和汗液排出。近年大量研究表明,肠道菌群的变化与高尿酸血症乃至痛风的发病密切相关,本文就高尿酸血症的发生与肠道菌群的相互关系,及目前研究进展进行综述,进一步探讨尿酸在肠道的代谢机制,旨在为降低血尿酸及治疗尿酸相关疾病提供新的思路。     

Hyperuricemia and gout in thyroid endocrine disorders.

OBJECTIVE: A significant correlation between thyroid function and purine nucleotide metabolism has been established in hypothyroidism. On the contrary, the relationship between hyperthyroidism and purine metabolism is more controversial. The present study evaluates the prevalence of hyperuricemia and gout in patients affected by primary hypothyroidism and hyperthyroidism. METHODS: We studied 28 patients with primary hypothyroidism and 18 patients with primary hyperthyroidism, all hospitalized because of endocrine dysfunction. All underwent a series of clinical, biochemical and instrumental evaluations; in particular, thyroid-stimulatin hormone (TSH), free thyroxine (fT4), blood urea, serum creatinine, creatinine clearance, serum and urinary uric acid levels were measured. RESULTS: In comparison to the prevalence reported in the general population, a significant increase of both hyperuricemia and gout was found in the hypothyroid patients, and of hyperuricemia in the hyperthyroid patients. In hyperthyroidism the hyperuricemia is due to the increased urate production, while in hypothyroidism the hyperuricemia is secondary to a decreased renal plasma flow and impaired glomerular filtration. CONCLUSIONS: Ourfindings confirm the data in the literature concerning the high prevalence of hyperuricemia and gout in hypothyroidism. It shows that hyperthyroidism can cause a significant increase in serum uric acid, as well, although lower than the hyperuricemia due to thyroid hormone deficiency.     

饮食干预对高尿酸血症和痛风患者的疗效分析

目的探讨营养宣教和饮食干预在高尿酸血症和痛风患者治疗中的作用。方法对45例高尿酸血症和痛风患者进行营养宣教,比较宣教前后患者对高嘌呤食物的知晓率;对患者分别进行低嘌呤饮食或药物治疗,并进行疗效观察与比较。结果通过营养宣教,患者对高嘌呤食物的知晓率显著提高（P〈0．01）;饮食干预或药物治疗均能够有效改善患者症状,并使其血尿酸值显著降低（P〈0．01）。结论对高尿酸血症和痛风患者进行饮食宣教和营养干预,能够有效降低患者血尿酸值,改善患者的临床症状。     

Endocrinopathies and uric acid metabolism

Evidence for the presence of uric acid abnormalities in acromegaly is equivocal, and the hyperuricemia seen post-adrenalectomy is related to the primary hypertensive state rather than to adrenal dysfunction.Hyperparathyroidism, hypoparathyroidism, hypothyroidism, and hyperthyroidism have all been documented to have alterations in uric acid metabolism. In these endocrinopathies, abnormalities of renal function appear to be the primary mechanistic factors in the pathogenesis of these changes in urate metabolism. However, nonrenal factors and parathyroid and thyroid hormones have not been fully evaluated as to their roles in altered purine metabolism.The relationship between carbohydrate intolerance and hyperuricemia or gout represents an extremely complex problem. It is clear that diabetic ketoacidosis is associated with increased serum uric acid concentrations concomitant with a decreased urinary urate excretion, and the mechanism for these derangements is well established. Despite the accumulated evidence favoring an increased incidence of carbohydrate intolerance in gouty patients, the actual incidence and the mechanism which relates carbohydrate and purine abnormalities remains elusive. Even though many factors such as race, obesity, age, and other parameters may effect both carbohydrate and uric acid metabolism, recent data point toward insulin deficiency and not insulin resistance as the cause for carbohydrate intolerance in gout.     

Clinical aspects of monosodium urate monohydrate crystal deposition disease (gout)

Gout is a clinical syndrome with a limited range of manifestations arising as a result of the deposition of crystals of monosodium urate, the final product of purine metabolism in humans. Hyperuricemia is a common chemical aberration that is most often mild and remains asymptomatic. Thus, hyperuricemia should be distinguished from gout, even though urate supersaturation is necessary for the expression of gout. Uric acid overproduction and diminished renal uric acid excretion are the major mechanisms resulting in hyperuricemia, and an understanding of the basis of hyperuricemia in individual gout patients is an important step in determining appropriate treatment and in identifying underlying disorders, offending drugs and toxins, and inherited enzyme defects, all of which can result in hyperuricemia and gout. A scheme is presented for the evaluation of patients with new-onset gout, along with a discussion of the relationships between gout/hyperuricemia and a variety of metabolic disorders that are unusually prevalent in gouty populations.     

中药四妙丸加味治疗痛风的临床观察

目的 探讨痛风及高尿酸血症患者的异同及四妙丸加味治疗痛风的机制.方法 观察30例缓解期痛风患者、32例高尿酸血症患者和31名健康对照者超敏C反应蛋白(hsCRP)、胰岛素抵抗、尿酸、胆固醇、甘油三酯的区别.痛风组服用中药四妙丸加味14 d后复查hsCRP、胰岛素抵抗和尿酸.结果 痛风组hsCRP显著高于高尿酸血症组及健康对照组(P＜0.01),服用中药治疗后痛风组hsCRP显著下降(P＜0.01),尿酸变化无统计学意义.结论 中药四妙丸加味可能是通过减轻炎症反应达到治疗目的 .     

Serum uric acid-lowering therapies: Where are we heading in management of hyperuricemia and the potential role of uricase

Although allopurinol has been available for approximately 50 years, hyperuricemia and its sequelae are not only prevalent, but the incidence and costs associated with this disorder continue to increase. However, several new therapies have been developed. Recombinant urate oxidase has been useful in the treatment of tumor lysis hyperuricemia, and pegylated urate oxidase shows promise in patients with hyperuricemia and gout. Febuxostat and Y-700 are new oral xanthine oxidase inhibitors that are in human clinical trials. Tailoring of antilipid therapy in selected hyperuricemic and hyperlipidemic patients with fenofibrate may be of benefit in lowering blood cholesterol and uric acid levels. Similarly, treatment of selected hyperuricemic patients who also are hypertensive with losartan or amlodipine may be beneficial in lowering blood pressure and hyperuricemia. Despite these advances, new treatments for hyperuricemia are needed.     

川东北地区原发性痛风的临床特点及发病危险因素分析

目的：探讨川东北地区原发性痛风的临床特点及发病危险因素。方法采用统一调查表,对583例原发性痛风患者及459例健康体检者进行临床调查及相关实验室指标检测,采用Logistic回归分析痛风的发病危险因素。结果①94．9％的患者首次发作时累及一个关节,其中累及第一跖趾关节者占68．6％。②痛风发作无诱因者占37．6％;有诱因者占62．4％,其中88．2％与饮食因素有关。③痛风并发痛风石者占12．2％,高血压者占35．7％,高脂血症者占66．9％。④并发痛风石者多发生于痛风后3～8年,其病程长于无痛风石患者,血尿酸（sUA）水平高于无痛风石患者（P均＜0．01）。⑤Logistic回归分析发现,高sUA、饮酒、BMI、高TG、高嘌呤饮食、高血压及吸烟均与痛风发病相关（P＜0．01或＜0．05）。结论原发性痛风发病受多因素影响,高sUA、饮酒、BMI、高TG、高嘌呤饮食、高血压及吸烟均可能增加其发病风险。     

Control of renal uric acid excretion and gout

PURPOSE OF REVIEW: Impaired renal uric acid excretion is the major mechanism of hyperuricemia in patients with primary gout. This review highlights recent advances in the knowledge of normal mechanisms of renal uric acid handling and derangement of these mechanisms in uric acid underexcretion. RECENT FINDINGS: The discovery of URAT1 has facilitated identification of other molecules potentially involved in uric acid transport in the renal tubules. Some of these molecules show gender differential expression in animal experiments. Sodium-dependent monocarboxylate cotransporters have been shown to transport lactate and butyrate, and may have roles in hyperuricemia associated with diabetic ketoacidosis and alcohol ingestion. Certain polymorphisms in SLC22A12 may be associated with the development of hyperuricemia or gout, although confirmation is needed. Mechanisms of hyperuricemia associated with uric acid underexcretion in patients with familial juvenile hyperuricemic nephropathy also remain to be clarified. Distal tubular salt wasting and compensatory upregulation of the resorption of sodium and uric acid in the proximal tubule may explain the hyperuricemia associated with this disorder. SUMMARY: Much progress has been made in understanding the mechanisms of renal uric acid handling. Elucidation of the mechanisms of hyperuricemia in patients with familial juvenile hyperuricemic nephropathy will shed light on the function of uromodulin, functional impairment of which eventually results in diminished uric acid excretion.     

无症状性高尿酸血症的诊断与治疗

尿酸是人体嘌呤代谢的产物.在正常情况下,人体每天尿酸的产生和排泄基本上保持动态平衡,凡是影响血尿酸生成和(或)排泄的因素均可以导致血尿酸水平增加.国际上将高尿酸血症(HUA)的诊断标准定义为男性血尿酸水平＞420 μmol/L(7 mg/dl),女性＞357 μmol/L(6 mg/dl),无痛风发作的HUA称为无症状...     

高尿酸血症/痛风流行病学特点及危险因素

高尿酸血症/痛风的患病率逐年攀升,呈现高流行、年轻化、男性高于女性、沿海高于内地的流行趋势.肥胖、高血压、高血脂、高血糖等与高尿酸血症/痛风的发生、发展密切相关.小剂量阿司匹林、袢利尿剂和噻嗪类利尿剂等药物亦可促进血清尿酸水平的升高.高尿酸血症是2型糖尿病、高血压、动脉粥样硬化、心血管事件、脑卒中和慢性肾脏病等疾病的独立危险因素,是痛风发作的最主要生化基础和最直接病因.对于高尿酸血症/痛风患者,应强调早期发现和早期治疗.     

心理应激与高尿酸血症患者血尿酸关系研究

目的探讨生活事件心理应激相关因素与高尿酸血症患者血尿酸水平之间的关系。方法采用生活事件量表对60例高尿酸血症患者精神刺激进行定性和定量研究分析,并通过实验室检测分析比较不同压力下高尿酸血症患者的一般资料及生化指标的差异,并进一步进行相关性分析和多元回归分析。结果将生活事件量表总分小于等于20分的患者纳入低压力组,总分大于20分的纳入高压力组。正性、负性生活事件出现频率最高的事件分别为突出的个人成就、晋级和提升等,以及工作学习中压力大、生活规律重大变动、对现职工作不满意等。高压力组的患者最近1年的痛风发作频率以及总胆固醇、三酰甘油、血肌酐、血尿酸、皮质醇水平显著高于低压力组(P<0.05)。生活事件总刺激量与总胆固醇、三酰甘油、血肌酐和血尿酸呈正相关,其中正性生活事件刺激量与总胆固醇和三酰甘油呈正相关,负性生活事件刺激量和尿酸呈正相关。以血尿酸为因变量的多元线性回归分析中,最近1年痛风发作频率和压力分组最终进入回归模型,该回归模型具有统计学意义F(2,54)=27.765(P<0.01),调整R^2=0.522。结论在生活事件中的家庭生活和工作上受到的刺激较大的高尿酸血症患者,精神心理压力与机体总胆固醇、三酰甘油、血尿酸水平升高有关,其中三酰甘油和总胆固醇的升高与正性生活事件有关,而血尿酸的升高则是与负性生活事件有一定关系。高尿酸血症的患者,其较高的压力水平和频发的痛风与血尿酸升高有关。     

原发性高尿酸血症患者发生痛风的前瞻性研究

目的 明确原发性高尿酸血症(HUA)患者发生痛风的危险因素.方法 对2004年山东沿海流行病学调查和本院健康体格检查高尿酸血症患者随访3年,主要观察指标为是否发生痛风,评估膳食因素对痛风发生的影响和患者血生化指标变化.结果 536例HUA患者,102例发生痛风,发生率为19%.年龄(OR=1.046,P＜0.05)、血尿酸(OR=1.021,P＜0.05)、空腹血糖(OR=1.021,P＜0.05)、甘油三酯(OR=1.008,P＜0.05)、蟹贝类摄入量(OR=5.992,P＜0.05)和啤酒摄入量(OR=1.012,P＜0.05)是HUA患者发生痛风的危险因素.结论 HUA患者蟹贝类、啤酒等过量摄入造成血尿酸波动是发生痛风的主要危险因素.调整糖脂代谢紊乱、减少高嘌呤食物摄入、控制血尿酸水平是减少痛风发作的重要措施.

Abstract：

Objective To determinate the risk factors of gout in patients with hyperuricemia.Methods Patients detected with hyperuricemia both in epidemiological survey of Shandong coastal areas in 2004 and in health examination of our hospital were followed up for three years to observe the incidence of gout, relationship of diet and gout, and changes of biochemical indicators.Results During 3 years, 102 patients (19%) out of 536 patients with hyperuricemia developed gout. Age(OR=1.046, P＜0.05), serum uric acid(OR=1.021, P＜0.05), fasting plasma glucose(OR=1.021, P＜0.05), triglyceride(OR=1.008, P＜0.05), tony crab intake ( OR=5.992, P＜0.05),and beer intake(OR=1.012, P＜0.05) were the risk factors of gout attack in patients with hyperuricemia.Conclusions Excess intake of tony crab and beer resulting in fluctuation of serum uric acid is the main risk factor of gout in patients with hyperuricemia. Correcting metabolic disorder of glucose and lipid, reducing the intake of high-purine food, and controlling the level of serum uric acid are the measures to reduce gout attack.     

痛风与脂代谢紊乱及肥胖的关系

目的探讨男性家系及散发痛风患者的临床、生化特征及痛风与脂代谢紊乱、肥胖的关系。方法选择初诊男性家系痛风354例(家系组)和初诊男性散发痛风1 347例(散发组),分析两组年龄、身高、体质量、体质量指数、腰围、臀围、腰臀比等临床特征,检测其甘油三酯、胆固醇、血尿酸等生化指标。同时,观察两组非诺贝特治疗6个月、1年患者生化指标的变化。结果初诊家系组与散发组中,超重与肥胖、腹型肥胖、高甘油三酯、高胆固醇、高尿酸指标均与痛风相关;家系组与散发组比较,腹型肥胖指标差异有统计学意义(P<0.05)。两组非诺贝特治疗6个月、1年后,甘油三酯、胆固醇、血尿酸与治疗前比较,差异有统计学意义(P均<0.05)。随着用药时间的延长,治疗作用更明显。结论不论家系或散发痛风患者,均易合并肥胖、脂代谢紊乱;治疗痛风的同时,应关注患者血脂变化。     

An epidemiologic study on pathogenesis of uric acid urolithiasis

Recently, the number of patients with gout and hyperuricemia has increased in Japan; therefore, we expected to find an increase in the number of uric acid stones in our study. We examined the frequency of uric acid stones and its relationship with the number of patients with gout and hyperuricemia or their nutritional state. We reviewed the records of 5477 patients with urolithiasis who visited our hospital between 1975 and 1993. During this period, the incidence of calcium-containing stones remained at 86%. The percentage incidence of uric acid and urate stones during the same period showed a steady increase to 7.2%. This increase was computed to be 3-fold that of 1975. The male gender dominates among the patients with uric acid and urate stones. We believe that the increases in the incidence of gout and hyperuricemia and alcohol consumption are responsible for this trend.     

Metabolic basis for disorders of purine nucleotide degradation

Purine nucleotide degradation refers to a regulated series of reactions by which human purine ribonucleotides and deoxyribonucleotides are degraded to uric acid in humans. Two major types of disorders occur in this pathway. A block of degradation occurs with syndromes involving immune deficiency, myopathy or renal calculi. Increased degradation of nucleotides occurs with syndromes characterized by hyperuricemia and gout, renal calculi, anemia or acute hypoxia. Management of disorders of purine nucleotide degradation is dependent upon modifying the specific molecular pathology underlying each disease state.     

血清尿酸与高尿酸血症相关疾病

尿酸是人体嘌呤碱基分解代谢终产物,经肾脏排泄。体内尿酸生成超过肾脏排泄时血清尿酸会显著升高,造成高尿酸血症。高尿酸血症与痛风、心血管疾病、肿瘤裂解综合征及肾脏疾病的引发或加剧密切相关。本文对血清尿酸的临床意义进行综述。     

Renal underexcretion of uric acid is present in patients with apparent high urinary uric acid output

OBJECTIVE: To compare renal handling of uric acid in patients with primary gout with that of a control group. METHODS: A case-control study of 100 patients with primary gout and 72 healthy controls was undertaken. Creatinine clearance, uric acid clearance, 24-hour uric acid urinary excretion, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, urinary uric acid to creatinine ratio, and glomerular uric acid filtered load were calculated using 24-hour urine samples. After treatment with allopurinol to achieve similar glomerular filtered load of uric acid, patients were again compared with controls. RESULTS: Patients with gout showed lower uric acid clearance, fractional excretion of uric acid, excretion of uric acid per volume of glomerular filtration, and urinary uric acid to creatinine ratio than controls at baseline, when patients showed hyperuricemia. Although the glomerular uric acid filtered load was much higher in patients with gout than controls, 24-hour uric acid excretion was not statistically different. After treatment with allopurinol, and achieving similar uric acid filtered loads, patients still showed lower figures than controls. When patients with 24-hour urinary uric acids levels >700 mg/day were compared with controls, they had lower uric acid clearance and fractional excretion of uric acid than controls, both at baseline and after achieving similar filtered loads with allopurinol therapy. CONCLUSIONS: Renal underexcretion is the main mechanism for the development of primary hyperuricemia in gout, but even patients showing apparent high 24-hour uric acid output show lower uric acid clearance than controls, indicating that relative, low-grade underexcretion of uric acid is at work.     

Phosphoribosylpyrophosphate synthetase superactivity. A study of five patients with catalytic defects in the enzyme

Superactive phosphoribosylpyrophosphate (PRPP) synthetases were characterized in fibroblasts and erythrocytes from 5 unrelated men with gout and/or hyperuricemia and uric acid overproduction. The kinetic basis of enzyme superactivity in all patients was increased maximal reaction velocity. Affinities of the enzymes for substrates and activators and responsiveness to inhibitors were normal, and levels of immunoreactive enzyme in patient and control fibroblast and erythrocyte extracts were comparable. Enzymes purified to homogeneity from 2 patients confirmed the presence of isolated catalytic defects. Altered physical properties of certain of the superactive enzymes suggested the presence of several distinctive structural defects among the aberrant forms. Fibroblasts from each affected patient showed increased PRPP concentration and generation, as well as accelerated rates of all PRPP-requiring purine nucleotide synthetic pathways. These findings support the concept that enzyme superactivity results in uric acid overproduction as a consequence of increased rates of PRPP and purine nucleotide synthesis. Cultured cells from female relatives of 2 patients showed evidence for the heterozygous carrier state, as measured both by enzyme activities and by rates of PRPP and purine synthesis. The clinical phenotype in 4 patients was limited to early adult-onset gout and its consequences, whereas the fifth patient expressed a familial constellation of hyperuricemia, sensorineural deafness, ataxia, and renal insufficiency. The severity of the derangements in PRPP synthetase and in PRPP and purine synthesis in cells from the 5 patients, however, was comparable. The neurologic accompaniments of enzyme superactivity found in 1 family described here, and in 2 others described previously, thus may not necessarily be consequences of primary defects in PRPP synthetase.     

Phosphoribosylpyrophosphate synthetase superactivity: A study of five patients with catalytic defects in the enzyme

Superactive phosphoribosylpyrophosphate (PRPP) synthetases were characterized in fibroblasts and erythrocytes from 5 unrelated men with gout and/or hyperuricemia and uric acid overproduction. The kinetic basis of enzyme superactivity in all patients was increased maximal reaction velocity. Affinities of the enzymes for substrates and activators and responsiveness to inhibitors were normal, and levels of immunoreactive enzyme in patient and control fibroblast and erythrocyte extracts were comparable. Enzymes purified to homogeneity from 2 patients confirmed the presence of isolated catalytic defects. Altered physical properties of certain of the superactive enzymes suggested the presence of several distinctive structural defects among the aberrant forms. Fibroblasts from each affected patient showed increased PRPP concentration and generation, as well as accelerated rates of all PRPP-requiring purine nucleotide synthetic pathways. These findings support the concept that enzyme superactivity results in uric acid overproduction as a consequence of increased rates of PRPP and purine nucleotide synthesis. Cultured cells from female relatives of 2 patients showed evidence for the heterozygous carrier state, as measured both by enzyme activities and by rates of PRPP and purine synthesis. The clinical phenotype in 4 patients was limited to early adult-onset gout and its consequences, whereas the fifth patient expressed a familial constellation of hyperuricemia, sensorineural deafness, ataxia, and renal insufficiency. The severity of the derangements in PRPP synthetase and in PRPP and purine synthesis in cells from the 5 patients, however, was comparable. The neurologic accompaniments of enzyme superactivity found in 1 family described here, and in 2 others described previously, thus may not necessarily be consequences of primary defects in PRPP synthetase.