Department of Nephrology, Amalia Fleming General Hospital, Athens, Greece.
Ren Fail. 2012;34(4):510-20. doi: 10.3109/0886022X.2011.653753. Epub 2012 Jan 20.
Hyperuricemia is particularly common in patients with arterial hypertension, metabolic syndrome, or kidney disease. Its role, however, as a risk factor for both renal and cardiovascular outcomes and in the context of the well-established interrelationship between cardiovascular disease and chronic kidney disease (CKD) is debated. For decades high serum uric acid levels were mainly considered the result of renal dysfunction and not a true mediator of renal disease development and progression. However, recent epidemiological studies suggest an independent association between asymptomatic hyperuricemia and increased risk of arterial hypertension, CKD, cardiovascular events, and mortality. Furthermore, data from experimental models of hyperuricemia have provided robust evidence in this direction. Hyperuricemia causes increased arterial pressure, proteinuria, renal dysfunction, and progressive renal and vascular disease in rats. The main pathophysiological mechanisms of these deleterious effects caused by uric acid are endothelial dysfunction, activation of local renin-angiotensin system, increased oxidative stress, and proinflammatory and proliferative actions. A small number of short-term, single-center clinical studies support the beneficial influence of pharmaceutical reduction of serum uric acid on total cardiovascular risk, as well as on renal disease development and progression. Hyperuricemia is probably related to the incidence of primary hypertension in children and adolescents, as serum uric acid lowering by allopurinol has an antihypertensive action in this group of patients. Finally, it is clear that adequately powered randomized controlled trials are urgently required to elucidate the role of uric acid in cardiovascular events and outcomes, as well as in the development and progression of CKD.
高尿酸血症在动脉高血压、代谢综合征或肾脏疾病患者中尤为常见。然而，其作为肾脏和心血管结局的风险因素的作用，以及在心血管疾病与慢性肾脏病（CKD）之间已确立的密切关系背景下，仍存在争议。数十年来，高血清尿酸水平主要被认为是肾功能障碍的结果，而不是肾脏疾病发展和进展的真正介导物。然而，最近的流行病学研究表明，无症状高尿酸血症与动脉高血压、CKD、心血管事件和死亡率的增加之间存在独立关联。此外，高尿酸血症的实验模型数据为此提供了有力的证据。高尿酸血症导致大鼠的动脉压升高、蛋白尿、肾功能障碍以及进行性肾和血管疾病。尿酸引起这些有害影响的主要病理生理机制是内皮功能障碍、局部肾素-血管紧张素系统的激活、氧化应激增加以及促炎和增殖作用。少数短期、单中心的临床研究支持通过药物降低血清尿酸对总体心血管风险以及肾脏疾病发展和进展的有益影响。高尿酸血症可能与儿童和青少年原发性高血压的发生有关，因为别嘌醇降低血清尿酸在该组患者中具有降压作用。最后，显然迫切需要进行足够大的随机对照试验，以阐明尿酸在心血管事件和结局以及 CKD 发展和进展中的作用。
