尿酸肾病

尿酸和肾脏的关系很早就引起了人们的注意。体内尿酸主要由肾脏排泄,肾功能障碍时可产生高尿酸血症,高尿酸血症又可引起肾脏损害。近年由于基础医学研究的深入,对于肾脏排泄尿酸的机制和尿酸产生肾脏损害的发生机理的阐述日臻完善,本文就肾脏对产生高尿酸血症的作用和尿酸肾病作一综述。肾脏对产生高尿酸血症的作用体内尿酸的产生和排泄保持着动态平衡,若尿酸产生过多或排出不足均能使血尿酸含量增高。血清尿酸浓度在正常人群分布并不一致,通常把男性超过7mg%、女性超过6mg%称为高尿酸血症。慢性高尿酸血症大约1/3为     

高尿酸血症及其肾脏损害18例

尿酸是人体中嘌呤代谢的最终产物。由于体内嘌呤代谢紊乱引起体内尿酸积聚或因肾脏排泄尿酸减少,均可引起高尿酸血症。高尿酸血症又是产生尿酸肾病的病因。现就我院1978～1986年收治的原发性高尿酸血症18例进行分析讨论。     

高尿酸血症肾病

尿酸是嘌呤代谢的终末产物。嘌呤代谢紊乱或尿酸排泄减少可引起高尿酸血症,尿酸盐沉积于肾脏引起的肾病变称为高尿酸血症肾病。病因和发病机理正常情况下,人体合成的尿酸1/3经肠道排出,2/3经肾排泄。尿酸经肾小球滤过、吸收、分泌和再吸收后,随尿排出。尿尿酸>700mg/d称为高尿酸尿     

甲状腺功能减退症与高尿酸血症

甲状腺功能减退症与高尿酸血症或痛风伴发比例高,甲状腺激素可直接作用于肾脏导致尿酸排泄减少,也可通过调节瘦素水平影响肾脏对尿酸排泄,同时高尿酸血症或痛风通过作用于下丘脑-垂体-甲状腺轴,影响甲状腺激素的合成及分泌,高尿酸血症也可刺激瘦素基因表达或减少其清除,从而影响甲状腺激素水平.甲状腺激素水平降低和血尿酸水平升高是代谢综合征的危险因素,胰岛素抵抗是代谢综合征的核心,故胰岛素抵抗可能是联系高尿酸血症与甲状腺功能减退症的关键环节.     

尿酸盐转运体在原发性高尿酸血症中的研究进展

尿酸是人体内嘌呤代谢的终产物,由于人体缺乏尿酸酶,不能降解尿酸为尿囊素,最终尿酸以尿酸盐形式由肾脏排出体外.尿酸为阴离子,有抗氧化作用,相比低等动物而言,在这一点上有其进化意义.但如果人体尿酸生成过多或者尿酸排出过少,将引起高尿酸血症,即:细胞外液的尿酸盐呈超饱和状态,一般认为血浆尿酸盐浓度超过正常值(男性＞420μmol/L,女性＞360 μmol/L)时,应考虑高尿酸血症.原发性高尿酸血症是一种先天性尿酸生成增加或排泄减少导致的疾病,10％的患者是因嘌呤代谢过程中的关键酶缺陷造成尿酸生成增加,而其余高达90％的高尿酸血症是由于肾脏对尿酸的排泄减少所致.肾脏近曲小管对尿酸的重吸收增加或分泌减少,是造成尿酸排泄减少的主要原因,这一过程主要依赖肾小管上皮细胞分布的尿酸转运蛋白[1].高尿酸血症引起的后果是严重的,如尿酸盐结晶沉积于关节引起痛风性关节炎;沉积于肾脏引起痛风性肾病和肾尿酸结石;刺激血管壁引起动脉粥样硬化、加重高血压和冠心病等;损伤胰腺B细胞诱发或加重2型糖尿病等[2-4].     

尿酸性肾病的治疗

尿酸性肾病的治疗中山医科大学肾脏研究所（广州，５１００８０）叶任高陆生才尿酸是嘌呤类物质分解代谢的终末产物，尿酸生成增多或肾脏排泄减少，均可引起高尿酸血症。一般认为，血尿酸男性＞３８６μｍｏｌ／Ｌ，女性＞３０９μｍｏｌ／Ｌ，可诊断为高尿酸血症。尿酸性...     

慢性肾脏病患者如何降尿酸治疗

正肾脏是尿酸排泄的主要器官。体内尿酸70%由肾脏排出,其余30%经胆管和肠道排出。由于嘌呤代谢紊乱使血尿酸生成过多,或由于肾脏病变排泄尿酸减少,均可引起高尿酸血症(HUA)。慢性肾脏病(CKD)肾功能不全是继发性HUA的常见原因。CKD患者HUA的特点临床观察到CKD患者发生HUA时血清肌酐升高和血尿酸升高往往不成比例,是由于机体能通过     

高尿酸血症肾病

高尿酸血症肾病北京医科大学肾脏病研究所（１０００３４）谨贻璞１高尿酸血症的发病机理当血清尿酸值男性高于４２０μｍｏｌ／Ｌ、女性高于３６０μｍｏｌ／Ｌ时，即称为高尿酸血症，其成因是机体尿酸生成过多或（和）排泄减少。１．１尿酸生成过多尿酸是人类瞟呤化合物...     

肾脏尿酸排泄在不同糖耐量状态下的变化

目的 研究T2DM自然病程的不同阶段肾脏尿酸排泄的变化,识别影响尿酸排泄的相关因素,为T2DM合并高尿酸血症个体化用药提供依据. 方法 收集168名无糖尿病病史的志愿者,行75 g OGTT,测定UA1b、Cr、Scr、UA与SUA,计算尿中尿酸/肌酐比值(UUA/CRE)和尿酸排泄分数(FUE). 结果 FUE在NGT(n=61)、糖尿病前期(IFG和/或IGR,n=55)和T2DM(n=52)组间差异无统计学意义;男性(P=0.007)、向心性肥胖(P=0.001)及高尿酸血症者(P＜0.0001)有相对低的FUE;WC是尿酸排泄独立的相关因素(P＜0.0001);在糖尿病和糖尿病前期合并高尿酸血症患者(n=16)中,仅有12.5％患者UUA/CRE低于正常人1％分位(根据16例男性和29例女性无高血压、无高血糖、无高尿酸计算). 结论 尿酸排泄降低是高尿酸血症发生的重要机制;尿酸排泄在糖尿病发生不同阶段无明显变化,大部分糖尿病和糖尿病前期合并高尿酸血症患者可能存在尿酸生成和排泄双重障碍,在治疗前和治疗期间测定UUA/CRE是必要的.     

老年人高尿酸血症和肾脏的关系

老年人高尿酸血症和肾脏的关系甚密切。本组血尿酸(SUA)男性为481.8μmol/L;女性为459.2 μmol/L。老年人高尿酸血症的发生,主要系由肾脏排泄尿酸的功能减退所致,而且多伴发肾小管功能减退,表现为远端肾小管功能受损,浓缩功能减退,以及近端肾小管功能被累及,使尿尿酸排泄减少与β_2微球蛋白(β_2-MG)重吸收不全。近端肾小管功能不全的早期发现以检测尿β_2-MG较尿溶菌酶为敏感。高尿酸血症多伴发高甘油三酯血症,两者呈显著正相关。     

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。     

Effects of Cilnidipine on Serum Uric Acid Level and Urinary Nitrogen Monoxide Excretion in Patients with Hypertension

The effects of cilnidipine on the serum uric acid level and urinary NO excretion in hypertensive patients were investigated. Blood and urine samples of 16 hypertensive outpatients were collected before and 2 months after cilnidipine therapy (10 mg). The serum uric acid level decreased significantly after cilnidipine treatment, while the uric acid–creatinine clearance ratio was unaffected. The cilnidipine medication produced a significant increase in urinary NO excretion, although amlodipine did not change it significantly. Therefore, cilnidipine has a profound antihypertensive effect and may reduce the serum uric acid level and increase NO production in the kidney.     

Single dose of rasburicase for treatment of hyperuricemia in acute kidney injury: a report of 3 cases

Severe hyperuricemia accompanied by the other comorbidities such as anuria, fluid overload, calcium-phosphate imbalance, and/or tumor lysis syndrome is one of the indications for dialysis in the setting of acute kidney injury. Rasburicase is used in different clinical conditions such as tumor lysis syndrome and uric acid nephropathy. Among referred patients to our center from 2008 to 2010, there were 3 patients who had an indication for dialysis because of hyperuricemia. Contributing factors to the acute kidney injury were multi-organ dysfunction, rapidly progressive glomerulonephritis, and spontaneous tumor lysis syndrome. None of the patients showed any response to treatment with bicarbonate and hydration. After rasburicase administration, serum uric acid level declined, and urine output increased. Treatment with a single low dose of rasburicase would be effective to decrease the serum uric acid level and reverse kidney injury secondary to uric acid nephropathy.     

Is thiazide-produced uric acid elevation harmful? Analysis of data from the Hypertension Detection and Follow-up Program

Interaction of thiazide diuretics and the serum uric acid and creatinine levels was studied in 3693 stepped care participants in the Hypertension Detection and Follow-up Program not receiving treatment at baseline. Among men grouped into quartiles by their level of uric acid at baseline, the upper quartile (average uric acid, 7.7 mg/dL [458 mumol/L]) had an average serum creatinine level of 1.2 mg/dL (106 mumol/L) and the lowest quartile (uric acid, 4.9 mg/dL [291 mumol/L]) had an average serum creatinine level of 1.1 mg/dL (97 mumol/L). Similar findings were present in women. Therapy with chlorthalidone or other thiazide-type diuretics tended to increase levels of uric acid and creatinine, but the increase in both was less in the upper quartile than in the lower quartile. Among individuals who were prescribed uric acid-lowering drugs, the level of serum creatinine increased just as much as in those whose uric acid level was not pharmacologically lowered. Baseline uric acid level was a weak predictor of mortality in men; the introduction of an interaction term for creatinine suggested that this effect was primarily restricted to those with elevated levels of both uric acid and creatinine at baseline. Change in uric acid level at one year after therapy was inversely correlated with mortality in men. There were few episodes of gout (only 15 recorded in five years among 3693 participants at risk). These results suggest that neither the baseline uric acid level nor the change in uric acid level produced by therapy injures the kidney. These results suggest no reason to lower uric acid levels pharmacologically in the treated hypertensive patient who is not gouty. They leave unanswered whether there is a predictive value to baseline uric acid level not explainable by other correlated cardiovascular risk factors.     

Uric acid excretion: quantitative assessment from spot, midmorning serum and urine samples.

Uric acid excretion can be measured in milligrams of urinary uric acid per decilitre of glomerular filtrate by obtaining the product of urinary uric acid and serum creatinine concentrations and dividing by the urine creatinine (all concentrations in mg/dL). In 29 normal adult men, the excretion rate in spot, midmorning samples was 0.4 +/- 0.1 (SD) mg of uric acid per decilitre of glomerular filtrate. Eight of 36 untreated gouty men excreted acid at a rate more than three standard deviations above normal. Excretion of uric acid is conveniently and physiologically assessed by this simple method.     

Cardiovascular and renal effects of hyperuricaemia and gout

A number of epidemiological studies have reported an association between serum uric acid levels and a wide variety of high-risk conditions including hypertension, insulin resistance, and kidney and cerebro-cardiovascular disease. All things considered, serum uric acid may induce cardiovascular and kidney events both directly and indirectly by promoting other well-known mechanisms of damage. While asymptomatic hyperuricemia is currently not considered to be an indication for urate lowering therapy, there is growing evidence indicating a linear relationship between pharmacological reduction in serum uric acid and incidence of cardiovascular and renal events.     

尿酸与肾脏疾病发生和预后关系的系统评价和荟萃分析

目的 系统评价尿酸与肾脏疾病发生和预后的关系,为防治肾脏疾病提供参考.方法 检索中国生物医学文献数据库(CBM)(1982年1月-2010年3月)、荷兰医学文摘(EMBASE)(1966年1月-2010年3月)以及美国医学索引(Medline)(1950年1月-2010年3月),筛选尿酸与肾脏疾病发生和预后的相关文献,只纳入队列研究.根据Newcastle-Ottawa质量评价量表评价纳入研究的偏倚风险,2名研究人员独立筛选、评价文献和收集数据.采用Stata10.0软件进行统计学分析.结果 共纳入21篇高质量队列研究文章,其中与肾脏疾病发生相关11篇,共276 801例研究对象;与肾脏疾病预后相关10篇,共3004例研究对象.对纳入研究中校正了除尿酸外其他影响肾脏疾病发生和预后因素的数据进行Meta分析,结果显示:(1)尿酸与肾脏疾病发生:尿酸水平升高会增加肾脏疾病的发生风险(RR=1.49,95%CI1.27～1.75).(2)尿酸与肾脏疾病预后:高尿酸可导致肾功能恶化(RR=1.35,95%CI1.12～1.63)和肾脏疾病患者死亡风险增加(RR=1.67,95%CI1.29～2.16).结论 尿酸是肾脏疾病发生和已患肾脏疾病患者预后不佳的独立危险因素.今后需开展高质量、长随访的临床试验,明确降低尿酸是否能降低肾脏疾病的发生风险和改善肾脏疾病患者的预后,为进一步明确尿酸与肾脏疾病的关系和高尿酸患者的防治提供直接依据.

Abstract：

Objective To evaluate the association of serum uric acid and the incidence and prognosis of kidney diseases systematically, so as to provide reference for the treatment and prevention of kidney diseases. Methods Literatures related to the associations between serum uric acid and incidence and prognosis of kidney diseases were selected from the Chinese Biomedical Literature Database ( CBM) (January 1982 to March 2010), EMBASE (January 1966 to March 2010) and Medline (January 1950 to March 2010) for cohort studies. Two researchers independently screened the studies, assessed the risk of bias of included studies using the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies and extracted data. Stata 10. 0 was used to calculate the pooled relative risk. Results Twenty-one eligible cohort studies were selected, of which 11 on incidence of kidney diseases (n =276 801 ) , and 10 on the prognosis of kidney diseases ( n = 3004). Meta analysis was performed based on data influencing incidence and prognosis factors of kidney diseases except for serum uric acid. The results showed, (1) uric acid and incidence of kidney diseases: hyperuricemia could increase the risk of kidney diseases ( RR = 1. 49, 95% CI 1. 27-1. 75) ; (2) uric acid and prognosis of patients with kidney diseases:hyperuricemia could deteriorate the kidney function (RR = 1. 35, 95%CI 1. 12-1.63) and increase the risk of mortality (RR = 1.67, 95% CI 1.29-2.16). Conclusion Uric acid is an independent risk factor for incidence of kidney diseases and poor prognosis of patients with kidney diseases. Further high quality clinical trials with long-term follow up should be conducted to determine whether lowering uric acid levels would be of clinical benefit in the prevention and treatment of kidney diseases, so as to provide direct evidence for clarifying correlation between uric acid and kidney diseases and the prevention and treatment for patients with high uric acid.     

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...     

Hyperuricaemia and gout in cardiovascular,metabolic and kidney disease

During the last century, there has been an increasing prevalence of hyperuricaemia noted in many populations. While uric acid is usually discussed in the context of gout, hyperuricaemia is also associated with hypertension, chronic kidney disease, hypertriglyceridaemia, obesity, atherosclerotic heart disease, metabolic syndrome, and type 2 diabetes. Here we review the connection between hyperuricaemia and cardiovascular, kidney and metabolic diseases. Contrary to the popular view that uric acid is an inert metabolite of purine metabolism, recent studies suggest serum uric acid may have a variety of pro-inflammatory, pro-oxidative and vasoconstrictive actions that may contribute to cardiometabolic diseases. Hyperuricaemia is a predictive factor for the development of hypertension, metabolic syndrome, type 2 diabetes, coronary artery disease, left ventricular hypertrophy, atrial fibrillation, myocardial infarction, stroke, heart failure and chronic kidney disease. Treatment with uric acid-lowering therapies has also been found to improve outcomes in patients with hypertension and kidney disease, in some but not all studies. In conclusion, uric acid is emerging as a potentially treatable risk factor for cardiometabolic diseases, and more clinical trials investigating the potential benefit of lowering serum uric acid are recommended in individuals with hyperuricaemia with and without deposition and concomitant hypertension, metabolic syndrome or chronic kidney disease.     

Efficacy of rasburicase therapy in obstructive renal failure secondary to urolithiasis: a novel therapeutic option

The overall incidence of nephrolithiasis-related acute and chronic renal failure is poorly known and surely underestimated. However, obstructive nephropathy represents a potentially curable form of kidney disease that often requires for managing an instrumentation of urinary tract. Rasburicase is an enzyme that transforms uric acid to allantoin, a compound more water soluble that will be excreted by the kidney more easily. Rasburicase has been proven to be an effective therapy for prevention of tumour lysis syndrome. But it also represents an interesting new option in managing hyperuricemia in patients with severe tophaceous gout. We administered rasburicase intravenously (0.20 mg/kg/day, for 2 days) in 2 adults with acute obstructive nephropathy from renal calculi, which was receiving temporary haemodialysis. Rasburicase produced a sharp polyuria 12-18 hours after its administration accompanied with a fast reduction of serum creatinine levels, that returned to normal range without further dialysis. If we suppose that rasburicase can pass through glomerular filter by its relatively low molecular weight, it could dissolve tubular uric acid crystals in acute renal failure associated to tumour lysis syndrome, providing the restoration of renal function. But we also could postulate that rasburicase can act in urinary tract, fragmentating renal calculi, promoting relief of obstructive uropathy and the resolution of renal failure. We suggest rasburicase should be tried in this new indication to prove its potential efficacy.