Méndez Landa Carlos Enrique
Department of Nephrology, General Hospital and Medical Unit Ambulatory Care, Mexican Institute of Social Security, Mexico City, Mexico.
Contrib Nephrol. 2018;192:8-16. doi: 10.1159/000484273. Epub 2018 Jan 23.
From a clinical point of view, uric acid has been dismissed as a cause of injury and renal progression, and the mechanisms by which uric acid directly causes renal injury have not been fully understood. Hyperuricemia is associated with metabolic syndrome, diabetes, hypertension, and kidney and cardiovascular diseases. Although it remains controversial whether hyperuricemia is a causal factor for kidney disease, kidneys play a major role in the regulation of serum uric acid levels.
Similar to the management of other substances, renal uric acid management occurs mainly in the proximal tubule. The elevation of uric acid in blood is mainly due to an increase in its intake or a defect in its secretion. The mechanisms of renal damage go beyond the deposition of crystals at the tubular level; in this sense, renal damage also contributes to the production of chemotactic cytokines, cell proliferation, and inflammation, with the development of afferent arteriolopathy, glomerular hypertrophy and tubulointersticial fibrosis. Nevertheless, whether or not hyperuricemia plays a causal role or simply is a marker arising in the course of each related disorder remains unresolved. Although a strong relationship between hyperuricemia and metabolic syndrome has been established through animal and epidemiological studies, the potential pathophysiological mechanisms by which uric acid contributes to this disease state are just beginning to be explained and clarified. Key Messages: Experimental studies performed in animals have limitations due to the differences that exist between humans and other mammals in purine metabolism and in renal uric acid handling. Additional experimental studies aimed at evaluating the effects of lowering urate levels on the courses of these disorders are warranted in the future.
从临床角度来看，尿酸一直被认为不是损伤和肾脏病变进展的原因，尿酸直接导致肾脏损伤的机制尚未完全明确。高尿酸血症与代谢综合征、糖尿病、高血压以及肾脏和心血管疾病相关。尽管高尿酸血症是否为肾脏疾病的病因仍存在争议，但肾脏在血清尿酸水平的调节中起主要作用。
与其他物质的处理类似，肾脏对尿酸的处理主要发生在近端小管。血液中尿酸升高主要是由于其摄入增加或分泌缺陷。肾脏损伤机制不仅限于肾小管水平的晶体沉积；从这个意义上讲，肾脏损伤还会导致趋化细胞因子的产生、细胞增殖和炎症，进而发展为入球小动脉病变、肾小球肥大和肾小管间质纤维化。然而，高尿酸血症是起因果作用还是仅仅是每种相关疾病过程中出现的一个标志物仍未解决。尽管通过动物和流行病学研究已证实高尿酸血症与代谢综合征之间存在密切关系，但尿酸导致这种疾病状态的潜在病理生理机制才刚刚开始得到解释和阐明。关键信息：由于人类与其他哺乳动物在嘌呤代谢和肾脏尿酸处理方面存在差异，在动物身上进行的实验研究存在局限性。未来有必要进行更多旨在评估降低尿酸水平对这些疾病病程影响的实验研究。
