高尿酸血症肾病.ppt

,高尿酸血症：病因还是标志？,HUA的流行病学,高尿酸血症 男性：8.2% 19.8% 女性：5.1% 7.6% 保守估计:目前我国约有1.2亿, 约占总人口的10% 高血压患者：25%未治疗者、50%服用利尿剂者、75% 的恶性高血压患者伴有高尿酸血症 肾脏病人群常见： 在刚开始透析的患者中约50%具有高尿酸血症 IgA 肾病患者中高尿酸血症的发生率为29.6%,尿酸的特性,弱的有机酸，168D 单价钠盐，分布于血浆、细胞外液,尿酸的代谢与排泄,人类嘌呤代谢的终末产物,来源,排泄,80%经肾排泄，肾小球滤过及肾小管分泌、重吸收 20%经胆道和肠道排泄,外源性：食物中的嘌呤，占体内尿酸20%， 内源性: 体内合成或核酸分解，占体内尿酸80%,在正常人体中，每天约有600mg尿酸产生，同时也有等量尿酸排出体外，以保持平衡状态,尿酸及嘌呤代谢,尿酸排泄减少,目前发现4个尿酸盐转运蛋白（离子通道）参与了人近曲小管对尿酸盐的转运： 生电型的尿酸盐转运子/通道hUAT 电中性的尿酸盐/阴离子交换子hURAT1 有机阴离子家族成员hOAT1、hOAT3 任何一个参与人近曲小管尿酸转运的蛋白质基因突变或多态、功能障碍都会导致其表达量或功能障碍，均可能引起尿酸排泄减少，属多基因遗传。,高尿酸血症的原因,高尿酸产生的原因？,American Journal of Kidney Diseases, Vol 52, No 5 (November), 2008: pp 994-1009,什么是高尿酸血症？,正常嘌呤饮食状态下，非同日两次空腹血尿酸水平 男420umol/l (7mg/dl） 女357umol/l (6mg/dl),无症状高尿酸血症合并心血管疾病诊治建议中国专家共识 ,常见高尿酸人群,Hypertension. 2003;41:1183-1190,高尿酸血症的分型,# 高尿酸血症患者低嘌呤饮食5 d后, 留取24 h尿检测尿尿酸水平 # 尿酸清除率:(Cua, 尿尿酸每分钟尿量/血尿酸) # 考虑到肾功能对尿酸排泄的影响, 以肌酐清除率(Ccr)校正, 根据Cua /Ccr 比值对HUA分型如下: 10%为尿酸生成过多型; 5%为尿酸排泄不良型; 5%10%为混合型,中国医师协会心血管内科医师分会, 中国医师协会循证医学专业委员会,临 床 表 现,痛风,临 床 表 现,肾结石,临 床 表 现,无症状高尿酸血症：患者往往合并肥胖、高血压、高脂血症、糖尿病、动脉硬化、冠心病、脑血管疾病等。,无症状性HUA,无症状性HUA是指血尿酸水平升高，但临床上没有尿酸盐沉积的任何症状和体征。 国际上将HUA定义为：正常嘌呤饮食状态下，非同日两次空腹血尿酸水平男420umol/l (7mg/dl）女357umol/l (6mg/dl),无症状性高尿酸血症的危害,肾脏损害？ 冠心病？ 心力衰竭？ 高血压？ 糖尿病？ 高甘油三酯血症？ 代谢综合征？,高尿酸：危害肾损害？,Cleve Clin J Med. 2008 Jul;75 Suppl 5:S13-6,高尿酸增加肾衰竭风险,Risk of renal failure in a prospective cohort study of 49,413 Japanese men stratified into quartiles by serum urate level. Risk was calculated relative to the quartile with “moderate” serum urate levels.5,高尿酸：危害肾损害？,Cumulative incidence of ESRD according to baseline serum uric acid level in men and women. The study period was from 1993 to 2000. To convert serumuric acid in mg/dL tomol/L, multiply by 59.48.,Am J Kidney Dis, 2004, 44: 642 - 650.,基线血尿酸水平越高，ESRD发生率越高,尿酸与冠心病,芝加哥心脏研究Levine W, Dyer AR , Shekelle RB , et al. Serum uric acid and 11.5- year mortality of middle2aged women : findings of the Chicago Heart Association Detection Project in Industry. J Clin Epidemiol ,1989,42:257-267 美国第一次全国健康与营养调查(NHANES研究) Freedman DS , Williamson DF , Gunter EW, et al. Relation of serum uric acid to mortality and ischemic heartdisease. The NHANES I Epidemiologic Follow2up Study. Am J Epidemiol. 1995, 141:637-644 MONICA研究 Meisinger, Christa, Koenig, Wolfgang, Baumert, Jens, Doring, Angeta. Uric Acid levels are associated with all-cause and cardiovascular disease mortality independent of Systemic Inflammation in Men from the general population: The MONICA/KORA Cohort study. Arteriosclerosis, Thrombosis and Vascular Biology 2008, 28(6): 1186-1192,尿酸是冠心病死亡独立危险因素,尿酸与冠心病,MRFIT研究 Gout and the risk of acute myocardial infarction. Arthritis Rheum 2006; 54:26882696 Krishnan E, Baker JF, Furst DE, Schumacher HR Jr. PIUMA研究 Relation between serum uric acid and risk of cardiovascular disease in essential hypertension. The PIUMA study. Hypertension 2000; 36:10721078 Verdecchia P, Schillaci G, Reboldi G, Rotterdam队列研究Uric acid is a risk factor for myocardial infarction and stroke: the Rotterdam Study. Stroke 2006; 37:15031507 Bos MJ , Koudstaal PJ 美国worksite研究 . Serum Uric Acid and Cardiovascular Events in Successfully Treated Hypertensive Patients. Hypertension. 1999;34:144-150 Michael H. Alderman; Hillel Cohen;,尿酸是心血管事件的独立危险因素,尿酸与心力衰竭,Hyperuricaemia and long-term outcome after hospital discharge in acute heart failure patients. Eur J Heart Fail. 2007, 9: 437-439 Pascual-Figal DA, Hurtado-Martinez Serum Level OF Uric Acid, Partly Secreted From the Failing Heart, is a Prognostic Marker in Patients With Congestive Heart Failure. Circ J 2006, 70: 1006-1011 Hiroshi Sakai, Takayoshi Tsutamoto,研究显示：HUA可作为急慢性心力衰竭死亡的独立预测指标,HUA与高血压,1 7. Jossa F , Farinaro E , Panico S , et al. Serum uric acid and hypertension: the Olivetti heart study. J Hum Hypertens. 1994 ,8 : 6672681Waddington C. Elevated uric acid can raise risk for CHD. Cardiol Today ,1999 ,2 :15. 2 SundstromJ ,Sullivan L D ,Agostino R B ,et al. Relation of serum uric acid to longitudinal blood pressure tracking and hypertension incidence. Hypertension ,2005 ,45 :28233 3 张红叶,李 莹,陶寿淇,周北凡,田秀珍,于学海,杨 军.血清尿酸与四年后血压变化及高血压发病的关系.高血压杂志,2001 ,9 (2): 160-163 4 Feig DI, Johnson RJ. Hyperuricemia in childhood primary hypertension. Hypertension 2003. 42: 247-252 5 Mazzali M, Hughes J, Kim YG, Jefferson JA, Kang DH, Gordon KL, Lan HY, Kivlighn S, Johnson RJ: Elevated uric acid increases blood pressure in the rat by a novel crystalindependent mechanism. Hypertension 2001，38: 11011106,血尿酸是高血压发病的独立危险因素,提示HUA 与原发性高血压有因果关系,证实高尿酸与高血压的因果关系,HUA 与糖尿病,Bickel C , Rupprecht HJ , Blankenberg S , et al. Serum uric acid as an independent predictor of mortality in patients with angiographically proven coronary artery disease. Am J Cardiol, 2002 ,89 :12-17 Feig DI, Johnson RJ. Hyperuricemia in childhood primary hypertension. Hypertension 2003. 42: 247-252,提示 长期HUA与糖耐量异常和糖尿病发病具有因果关系,HUA与高甘油三酯血症,Zalokar J, Lellouch J, Jean R, et al. Kuntz.epidemiology of serum uric acid and gout in franchmen. J Chron Dis, 1974,27:59-75 Conen D, Wietlisbach V, Bovet P, et al. Prevalence of hyperricemia and relation of serum uric acid with cardiovascular risk factors in a developing country. BMC Pub Heal, 2004, 25:9-17 邵继红，沈洪兵，莫宝庆，徐耀初. 社区人群高尿酸血症危险因素的病例 对照研究. 中华流行病学杂志 2004，25（8）：688-690. Nakanishi N, Tatara K, Nakamura K, et al. Risk factors for the incidence of hyperuriceamia: a 6-year longitudinal study of middle-aged Japanese men. Int J Epedemiol, 1999,28:888-893 Balasubramanian T. Uric Acid or I-methyl uric Acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in wistar rats. Scientific World J, 2003, 5:930-936. 张浩军，张冰，刘小青. 小鼠高尿酸高脂血症复合模型初探. 北京中医药大 学学报，2001，24（6）：29-30,一致显示血尿酸和甘油三酯之间有相关性,基础甘油三酯是未来HUA独立预测因素,提示：尿酸对甘油三酯代谢有一定影响,HUA与代谢综合征,代谢综合征之父Reaven教授提出将HUA纳入代谢综合征 Bradna P. Gout and diabetes.VnitrLek,2006,52(5):488-492 HUA常与代谢综合征各项指标伴发,有心血管疾病危险因素人群中高尿酸血症的发生率及其相关因素. 首都医科大学学报. 张立晶，胡大一，杨进刚，许玉韵，李田昌，王国宏，史旭波 2005，26（4）：520-524,高 尿 酸 血 症 肾 病,尿酸是否导致肾病，多年来一直存在争议？,Does hyperuricemia affect mortality? A prospective cohort study of Japanese male workers. Epidemiol 2000; 10:403409 Tomita M, Mizuno S, Yamanaka H, et al.,Significance of hyperuricemia as a risk factor for developing ESRD in a screened cohort. Am J Kidney Dis 2004; 44:642650 Iseki K, Ikemiya Y, Inoue T, Iseki C, Kinjo K, Takishita S.,Relationship of Uric Acid With Progression of Kidney Disease. Am J Kidney Dis 50:239-247 Michel Chonchol,Michael G. Shlipak, Ronit Katz,Mark J. Sarnak,Anne B.,Elevated UricAcid Increases the Risk for Kidney Disease. J Am Soc Nephrol, 2008. doi: 10.1681/ASN.2008010080 Rudolf P. Obermayr, Renate Klauser-Braun.,Use of Allopurinol in Slowing the Progression of Renal Disease Through its Ability to Lower Serum Uric Acid Level.Am J Kidney Dis 2006:47:51-59 Yui-Pong Siu, MRCP, Kay-Tai Leung, MRCP,尿酸与肾损害？,高尿酸血症肾病病理生理基础,尿酸结晶启动炎症反应：激活补体系统、炎性细胞、释放炎症因子及细胞因子，使局部炎症反应放大。 尿酸盐结晶导致梗阻 主要机制：导致肾小球前动脉病变、激活RAS系统和COX2从而血压升高；尿酸是血管平滑肌细胞的有丝分裂原，直接刺激血管平滑肌细胞增殖。,高尿酸血症肾病的临床分型,急性尿酸性肾病：如横纹肌溶解、肿瘤。往往导致ARF。机制为尿酸在远端肾单位的肾小管形成结晶。 慢性尿酸性肾病：首先排除继发性因素。 Scr132umol/L, UA536umol/L Scr132176umol/L, UA595umol/L Scr176umol/L,UA714umol/L,病 理,急性尿酸性肾病：管腔内可见尿酸盐结晶 慢性尿酸性肾病：小管间质的慢性病变，尿酸在远端小管和间质沉积，炎性细胞的浸润，长期可见小球硬化，血管硬化,实验室检查,尿液检查：PH，24H尿尿酸800mg.600mg，判断排泄和生成。 血尿酸：空腹8小时。正常男性：149416；女性89387 影像学检查 肾活检 基因异常及遗传病的检查,治 疗,尿酸一把双刃