山东沿海女性居民血尿酸影响因素及与代谢综合征防治切点的研究

背景:沿海居民血尿酸的影响因素如何?血尿酸与代谢综合征防治切点如何?目前尚无中国人资料。目的:明确山东沿海20岁以上女性血尿酸与代谢综合征的关系。设计:随机、分层、整群抽样调查。单位:青岛大学医学院附属医院内分泌科。对象:于2004-05/10对山东沿海五市(青岛、日照、烟台、威海和东营)常住女性居民进行调查。年龄20～80岁,常住5年及5年以上,以家庭为单位的自然人群。方法:采用入户调查和现场调查相结合的方式,第1天填写调查问卷,第2天清晨采空腹血做血尿酸检测,对尿酸值高于正常的第3天复查并进行痛风和高尿酸血症的防治教育。主要观察指标:①一般情况调查:包括健康状况、饮食、体力活动、劳动强度和经济情况。②营养调查:分食物摄入频率调查和膳食调查两部分。③测量身高、体质量、腰围、臀围、血压、体质量指数。④测定空腹血糖、血尿酸、总胆固醇、三酰甘油、高密度脂蛋白胆固醇、尿素氮、肌酐含量。结果:①随着血尿酸浓度的升高,收缩压、舒张压、脉压、体质量指数、腰围、腰臀比、尿素氮、肌酐、三酰甘油、总胆固醇也逐渐升高,血尿酸280～319μmol/L、血尿酸320～349μmol/L、血尿酸>350μmol/L(高尿酸血症)三组上述指标均明显高于血尿酸<280μmol/L组(P<0.05～0.01),而高密度脂蛋白胆固醇随血尿酸浓度的升高而降低(P均<0.01)。②高血压、脂代谢紊乱、超重和肥胖、糖代谢紊乱及代谢综合征的患病率随着尿酸值的升高而升高;与血尿酸<280μmol/L组比较,血尿酸280～319μmol/L、血尿酸320～349μmol/L和高尿酸血症组发生代谢综合征的OR值分别为2.29(95%CI:1.81～2.89),4.15(95%CI:3.10～5.55),4.96(95%CI:3.85～6.39)。③非条件Logistic多元逐步回归分析显示年龄、高血压、食贝类量、尿素氮、肌酐、三酰甘油、腰臀比、轻体力活动为女性高尿酸血症独立的危险因子,高密度脂蛋白胆固醇为保护因素。结论:山东沿海女性代谢综合征患病率随血尿酸值的升高而升高,血尿酸超过280μmol/L应作为代谢综合征防治切点。控制代谢综合征,减少贝类等含高嘌呤海产品的摄入是预防高尿酸血症的发生的措施之一。临床医师应警惕高尿酸血症致病作用。     

Uric acid promotes an acute inflammatory response to sterile cell death in mice

Necrosis stimulates inflammation, and this response is medically relevant because it contributes to the pathogenesis of a number of diseases. It is thought that necrosis stimulates inflammation because dying cells release proinflammatory molecules that are recognized by the immune system. However, relatively little is known about the molecular identity of these molecules and their contribution to responses in vivo. Here, we investigated the role of uric acid in the inflammatory response to necrotic cells in mice. We found that dead cells not only released intracellular stores of uric acid but also produced it in large amounts postmortem as nucleic acids were degraded. Using newly developed Tg mice that have reduced levels of uric acid either intracellularly and/or extracellularly, we found that uric acid depletion substantially reduces the cell death–induced inflammatory response. Similar results were obtained with pharmacological treatments that reduced uric acid levels either by blocking its synthesis or hydrolyzing it in the extracellular fluids. Importantly, uric acid depletion selectively inhibited the inflammatory response to dying cells but not to microbial molecules or sterile irritant particles. Collectively, our data identify uric acid as a proinflammatory molecule released from dying cells that contributes significantly to the cell death–induced inflammatory responses in vivo.     

Physiology and biochemistry of uric acid

In humans, uric acid is the final breakdown product of unwanted purine nucleotides. Uric acid is the last stage in purine degradation, because humans lack the enzyme uricase which converts uric acid into allantoin. Uric acid has profound beneficial effects since it scavenges potential harmful radicals in our body. However, in conjunction with genetic or environmental factors, uric acid can cause significant health problems, leading to kidney stones when it builds up in the kidneys and to gout when crystals accumulate in the joints. The levels of uric acid in the blood must be tightly controlled to minimize these detrimental effects. Normally, the body eliminates enough uric acid in the kidney, and in part also through the intestines, to keep its concentration at a healthy level in the blood (approximately 300 microM). In patients with gout or kidney stone disease, however, the body either produces excessive amounts of uric acid or its ability to eliminate uric acid is disturbed in some way. In the kidney, uric acid is reabsorbed via the uric acid transporter URAT1. This transporter is the major mechanism for regulating blood uric acid levels and therefore may prove an interesting target for future drug development.     

2型糖尿病血尿酸水平的相关因素

目的　研究 2型糖尿病血尿酸相关因素 ,探讨血尿酸水平在代谢综合征等发病中的作用。方法　 4 32例 2型糖尿病按血尿酸水平分两组 ,观察血尿酸与各指标的相关性及两组的合并症情况。结果　血尿酸与甘油三酯、总胆固醇、BMI、血压等呈正相关 (P<0 .0 1) ,与 Hb A1c、HDL- C呈负相关 (P<0 .0 1) ,与病程、L DL- C无相关 (P>0 .0 5 ) ;高尿酸组的代谢综合征等患病率明显升高。结论　 2型糖尿病血尿酸与多因素相关 ,提示 2型糖尿病高尿酸血症是代谢综合征等发病的危险因素之一。     

Hyperuricemia in glycogen storage disease type I. Contributions by hypoglycemia and hyperglucagonemia to increased urate production.

Studies were performed to determine whether hypoglycemia or the glucagon response to hypoglycemia increases uric acid production in glycogen storage disease type I (glucose-6-phosphatase deficiency). Three adults with this disease had hyperuricemia (serum urate, 11.3-12.4 mg/dl) and reduced renal clearance of urate (renal urate clearance, 1.1-3.1 ml/min). These abnormalities were improved in one patient by intravenous glucose infusion for 1 mo, suggesting a role for hypoglycemia and its attendant effects on urate metabolism and excretion. A pharmacologic dose of glucagon caused a rise in serum urate from 11.4 to 13.0 mg/dl, a ninefold increase in urinary excretion of oxypurines, a 65% increase in urinary radioactivity derived from radioactively labeled adenine nucleotides, and a 90% increase in urinary uric acid excretion. These changes indicate that intravenous glucagon increases ATP breakdown to its degradation products and thereby stimulates uric acid production. To observe whether physiologic changes in serum glucagon modulate ATP degradation, uric acid production was compared during saline and somatostatin infusions. Serum urate, urinary oxypurine, radioactivity, and uric acid excretion increased during saline infusion as patients became hypoglycemic. Infusion of somatostatin suppressed these increases despite hypoglycemia and decreased the elevated plasma glucagon levels from a mean of 81.3 to 52.2 pg/ml. These data suggest that hypoglycemia can stimulate uric acid synthesis in glucose-6-phosphatase deficiency. Glucagon contributes to this response by activating ATP degradation to uric acid.     

Renal disease from excess uric acid

Excess uric acid or urate deposition is a common element in three different forms of renal disease: acute uric acid nephropathy, chronic urate nephropathy, and uric acid nephrolithiasis. Clinical features vary with each form. Therapy is directed at decreasing production of uric acid, increasing its solubility, or both. When possible, preventive measures are taken.     

Drugs to lower uric acid levels. How to avoid misuse in gouty arthritis

Several points regarding the use of drugs to lower uric acid levels deserve emphasis. First, these agents are not useful in the management of acute gout. Second, all forms of the drugs should be initiated at low dose with gradual increments to achieve a serum uric acid level between 5 and 6 mg/dL. There are no data to support the widely presumed notion that dropping the uric acid level to a very low range (1 to 3 mg/dL) hastens resorption of tophi or improves joint function. Third, the uricosuric agents probenecid (Benemid) and sulfinpyrazone (Anturane) interact with a number of drugs, and both the patient and physician should be aware of this. Finally, and most important, careful and frequent monitoring is needed during the first several months of therapy with these drugs.     

Diagnostic value of uric acid to differentiate transudates and exudates.

Uric acid is known to be an end product of purine metabolism. Increases in uric acid may be found in clinical conditions associated with tissue hypoxia. We have investigated the value of uric acid to differentiate between a transudate and exudate. In this study, we measured uric acid in the pleural fluid and the serum of 110 patients, 30 women and 80 men with a mean age of 49.5+/-19 years. Light's criteria were used to differentiate between a transudate and exudate. Mean serum uric acid was 496.7+/-153.4 micromol/l in patients with transudates and 291.3+/-143.1 micromol/l in patients with exudates. Mean pleural fluid uric acid was 487.7+/-165 micromol/l in patients with transudates and 279.9+/-142.1 micromol/l in patients with exudates. These data showed that the levels of serum and pleural uric acid were higher in transudates than exudates (p<0.01). However, there was no significant difference between pleural fluid/serum uric acid ratio of the two patient groups (p>0.05). The specificity and sensitivity of pleural uric acid for diagnosis of transudate effusions were 73% and 80.6%, respectively. The specificity and sensitivity of pleural uric acid for diagnosis of transudate effusions from exudates without malignancy were 71.8% and 91.7%, respectively. The sensitivity and specificity of pleural lactate dehydrogenase for diagnosis of exudates were 82% and 89%; the sensitivity and specificity of pleural fluid/serum lactate dehydrogenase were 85% and 89%; the sensitivity and specificity of pleural fluid/serum protein were 91% and 89%, respectively. Using all three of Light's criteria together, the sensitivity was 91% and its specificity was 94%. Our findings indicate that determination of uric acid in pleural fluid may be of diagnostic value in differential diagnosis of transudates and exudates. The sensitivity of pleural uric acid measurement was higher for exudates without malignancy. However, Light's criteria remain the best means of separating transudates from exudates.     

Altered uric acid levels and disease states

Altered serum uric acid concentrations, both above and below normal levels, have been linked to a number of disease states. An abnormally high uric acid level has been correlated with gout, hypertension, cardiovascular disease, and renal disease, whereas a reduced uric acid concentration has been linked to multiple sclerosis, Parkinson's disease, Alzheimer's disease, and optic neuritis. Historically, uric acid has been considered a marker of these disease states. Recent studies, however, have provided evidence that uric acid may actually play a role in the development or progression of such diseases. As a result, the manipulation of uric acid concentrations is now either included in, or being investigated for, the treatment of a variety of disease states.     

维持性血液透析患者血尿酸水平及变异性与死亡的关系

目的探讨维持性血液透析患者血尿酸水平及变异性与死亡发生之间的关系。方法回顾性分析2008年1月至2011年9月在首都医科大学附属北京友谊医院血液透析中心接受维持性血液透析治疗患者的临床资料,统计每个患者血尿酸平均值和变异性,根据死亡患者血尿酸平均值的平均值及变异性平均值将患者为高尿酸高变异组(1组)、高尿酸低变异组(2组)、低尿酸高变异组(3组)、低尿酸低变异组(4组),计算各组病死率,并作两两比较,进一步对上述四组进行合并后再分析,按死亡组患者血尿酸平均值的平均值(364.08 mmol/L)作为界值,将所有患者分为高尿酸组(A组)和低尿酸组(B组),统计两组病死率并作比较,按死亡组患者血尿酸变异性(50.89 mmol/L)将所有患者分为:高变异性组(C组)和低变异性组(D组)统计两组病死率并做比较,将血尿酸与透前血肌酐、尿素、胆固醇、白蛋白水平做线性回归分析。结果①死亡组血尿酸平均值、白蛋白的平均值、肌酐的平均值、尿素的平均值、血红蛋白的平均值均低于存活组(P<0.05),而年龄和血尿酸变异性均高于存活组(P<0.05)。②年龄和尿酸变异性是发生MHD患者死亡的独立危险因素,肌酐、血红蛋白则不是MHD患者死亡发生的独立危险因素。③无论平均值大小,尿酸变异性大的患者病死率高于死变异性小的患者(P<0.001)。当变异性≥50.89 mmol/L时,尿酸平均值小的患者病死率高于尿酸平均值大的患者(P=0.099);当变异性<50.89 mmol/L时,尿酸平均值小的患者病死率高于尿酸平均值大的患(P<0.003)。④尿酸与营养指标(尿素、肌酐)呈正的直线相关。结论维持型血液透析患者变异性大(≥50.89mmol/L)时,尿酸平均值对病死率无影响。尿酸变异性小(<50.89 mmol/L)时,尿酸平均值小的病死率高。尿酸可能是反应营养状态指标之一,受其他营养指标影响。     

The stability of uric acid in ammonium hydroxide

We examined the stability of uric acid in dilute aqueous ammonium hydroxide solution by mass spectrometry. Uric acid decomposes in ammonium hydroxide even as dilute as 15 mmol/L when the mole ratio of ammonium hydroxide to uric acid is 50:1. There are at least four products of the decomposition, two of which have been identified as allantoin and urea. The slope of the decomposition curve indicates that uric acid is destroyed at an initial rate of 2-3% per hour. In ammonium hydroxide at a concentration of 1 mmol/L and a mole ratio of ammonium hydroxide to uric acid of less than or equal to 3.4, uric acid is not detectably decomposed. Evidently, any method for determination of uric acid that involves treating the analyte with ammonium hydroxide before analysis may destroy it. Therefore, a published method described as being "definitive" for uric acid (J Clin Chem Clin Biochem 1985; 23:129-35) could produce incorrect results because it involves storing the uric acid in 15 mmol/L ammonium hydroxide at a mole ratio of ammonium hydroxide to uric acid of greater than 120:1.     

依达拉奉治疗不影响不同尿酸水平急性缺血性卒中患者的预后

目的:探讨依达拉奉治疗急性缺血性卒中患者尿酸水平与90d时临床结局的关系。方法:回顾性研究发病24h内入院的且改良Rankin量表(ModifiedRankinScale,MRS)评分<2的缺血性卒中患者。以尿酸水平中位数值(333μmol/L)作为临界值将患者分为低尿酸(≤333μmol/L)组和高尿酸(>333μmol/L)组,并比较了90d时两组患者的临床资料及良好预后(MRS<2)的关系。进一步研究使用及未使用依达拉奉的尿酸水平与90d时结局指标之间的关系。结果:高尿酸组男性、高血压、心房颤动和心源性卒中的比例高于低尿酸组。高尿酸组90d时MRS<2的患者比例也较高(P=0.013);但在多因素分析中,尿酸与良好结局指标之间无独立相关性(OR1.30,95%CI:0.94~1.71)。在亚组分析中,高尿酸组中未使用依达拉奉治疗的患者90d时MR S<2的人数多于低尿酸组(OR 2.87,95%CI:1.20~7.16),但使用依达拉奉的高尿酸组与低尿酸组患者之间则无相关性。结论:在急性缺血性卒中患者中,依达拉奉治疗后90d时高尿酸水平与良好预后之间的关系不明显。     

Diagnosis and prevention of uric acid stones

Uric acid stones occur in 10% of all kidney stones and are the second most-common cause of urinary stones after calcium oxalate and calcium phosphate calculi. The most important risk factor for uric acid crystallization and stone formation is a low urine pH (below 5.5) rather than an increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrhea or severe dehydration. Uric acid stone disease can be prevented and these are one of the few urinary tract stones that can be dissolved successfully. The treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml daily), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary alkalization with potassium citrate or sodium bicarbonate is a highly effective treatment, resulting in dissolution of existing stones. Urinary uric acid excretion can be reduced by a low-purine diet. Potassium citrate is the treatment of choice for the prevention of recurrence of uric acid calculi. Allopurinol reduces the frequency of stone formation in hyperuricosuric patients with recurrent uric acid stones and/or gout.     

The enzymatic spectrofluorimetric determination of uric acid in microsamples of plasma by using p-hydroxyphenylacetic acid as a fluorophor.

A sensitive spectrofluorimetric micromethod for the determination of uric acid is presented together with its application to human and rat plasma. The method is based on the reactions or uricase and peroxidase coupled with p-hydroxyphenylacetic acid as a fluorophor. There is a very wide range of proportionality between the concentration of uric acid and the increase of fluorescence intensity. 10 ng of uric acid is still determinable. At most 25 mul of human or 50 mul of rat plasma is sufficient to obtain the accurate valve of endogenous plasma uric acid concentration. The uric acid levels of normal human and rat plasma measured by present method were within the ranges of concentrations previously reported. A comparative study of this method with a standard assay method is also presented.     

Primary hyperuricemia due to decreased renal uric acid excretion

Hyperuricemia reflects extracellular fluid supersaturation for uric acid. Although dietary, genetic, or disease-related excesses in urate production underlie hyperuricemia in some cases, impaired renal excretion of uric acid is the dominant cause of hyperuricemia. This type of hyperuricemia may be primary (idiopathic) and unassociated with an identifiable disorder. Two important candidates that may affect renal urate excretion were identified recently. One is an organic anion transporter (OAT) family member called urate transporter (URAT) 1. URAT1 has highly specific urate transport activity, exchanging this anion with others including most of the endogenous organic anions and drug anions that are known to affect renal uric acid transport. Another is uromodulin (UMOD), which is the key protein for the pathogenesis of familial juvenile hyperuricemic nephropathy that is characterized by early onset of hyperuricemia and renal failure. The role of these proteins in the cause of hyperuricemia is under investigation.     

Serum uric acid--a cardiovasular risk factor?

Serum uric acid represents an important, independent risk factor for cardiovascular and renal disease in patients with hypertension, heart failure, or diabetes. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events in patients with diabetes. Although the mechanism(s) by which uric acid may play a pathogenetic role in cardiovascular disease is unclear, hyperuricemia is associated with deleterious effects on endothelial dysfunction, oxidative metabolism, platelet adhesiveness, hemrheology, and aggregation. Whether a reduction in uric acid impacts CV and renal disease remains to be determined. However, recent findings from LIFE in hypertensive patients with LVH suggest the possibility that a treatment-induced decrease in serum uric acid may indeed attenuate cardiovascular risk. Almost one third of the treatment benefit of a losartan-based versus atenolol-based therapy on the composite endpoint (death, myocardial infarction, or stroke) may be ascribed to differences in achieved serum uric acid levels. Clearly, randomized clinical trials are needed to investigate further the long-term cardioprotective benefits issue of reducing hyperuricemia in hypertensive patients.     

Idiopathic hyperuricemia with overproduction of uric acid

Idiopathic hyperuricemia is generally defined as hyperuricemia caused by unknown origin. Idiopathic hyperuricemia is categorized as overproducing or underexcretion of uric acid. Overproduced uric acid is caused by increased biosynthesis of purine bodies, hypermetabolization of purine bodies, or increased intake of dietary purine bodies. Idiopathic hyperuricemia with overproducing uric acid can be diagnosed by amount of excreted uric acid in the urine. Recently it has been identified that hypertension are frequently associated with myogenic hyperuricemia converted from overproduced hypoxanthine in the skeletal muscles. Some anti-hypertensive drugs including alpha1 blocker, ACE inhibitor, alphabeta blocker, or long-acting Ca blocker attenuated the myogenic hyperuricemia. Thus, these drugs may be helpful in the management of hypertension with hyperuricemia.     

血尿酸增高与急性脑梗死相关性研究

目的探讨血清尿酸增高与急性脑梗死的相关性。方法将54例急性脑梗死患者设为研究组,55例健康体检者设为对照组,检测两组血尿酸、血糖、甘油三酯、总胆固醇,对检测结果进行相关分析。结果研究组血尿酸、血糖、甘油三酯、总胆固醇检测结果均显著高于对照组（P〈0．05或0．01）;血尿酸增高及血糖、总胆固醇升高与急性脑梗死的发生均呈显著正相关（P〈0．05或0．01）。结论急性脑梗死患者血尿酸水平显著高于正常人群,且血尿酸增高与血糖、总胆固醇升高一样,均是急性脑梗死的独立危险因素,与急性脑梗死的发病有显著相关性。     

Plasma uric acid concentration related to the urinary excretion of aldosterone and of electrolytes in normal subjects.

1. The relations between the concentration of plasma uric acid and urinary excretion of aldosterone, sodium and potassium, were studied in ten healthy males on a diet containing 160 mmol of sodium and 90 mmol of potassium per day. 2. Plasma uric acid correlated positively with aldosterone excretion and this correlation was statistically independent of sodium and potassium excretion. 3. Plasma uric acid correlated positively with potassium excretion and negatively with the urinary sodium/potassium ratio. There was no significant simple correlation with sodium excretion but the partial correlation of plasma uric acid and sodium excretion was negative and significant when excretion of aldosterone and potassium were held constant.     

吲达帕胺和氨氯地平对血尿酸的影响

目的：探讨吲达帕胺和氨氯地平在治疗高血压病中对血尿酸的影响。方法：２６３例高血压病人共分成两组，分别行吲哒帕胺和氨氯地平降压治疗，用药半年后测定血尿酸。结果：吲达帕胺组血尿酸比氨氯地平组明显升高，百分率分别为４２．２２％和２１．０９％，两组经检验后，差异有统计学意义（Ｐ〈０．０１）。结论：吲哒帕胺治疗高血压病时，血尿酸会明显升高，故对心肾功能不全及痛风患者需慎用，氨氯地平对血尿酸影响较小，相对较安全。