Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX.
Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX; Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX.
Semin Nephrol. 2020 Nov;40(6):564-573. doi: 10.1016/j.semnephrol.2020.12.003.
Uric acid is an end product of purine metabolism in human beings. An unusual and still unexplained phenomenon is that higher primates have relatively high uric acid levels in body fluids owing to a combination of absence of degradation and renal retention. The physiologic purpose of high uric acid levels still is enigmatic, but the pathobiologic burden is a variety of crystallopathies owing to the low aqueous solubility of uric acid such as gouty arthritis and acute uric acid nephropathy. In the urinary space, three distinct conditions result from chronic uric acid and/or urate precipitation. The first and most common variety is uric acid urolithiasis. In this condition, urate is a victim of a systemic metabolic disease in which increased acid load to the kidney is coupled with diminished urinary buffer capacity owing to defective ammonium excretion, resulting in titration of urate to its sparingly soluble protonated counterpart, uric acid, and the formation of stones. Uric acid is the innocent bystander of the crime. The second variety is hyperuricosuric calcium urolithiasis, in which uric acid confers lithogenicity via promotion of calcium oxalate precipitation by multiple mechanisms involving soluble, colloidal, and crystalline urate salts. Uric acid is the instigator of the crime. The third and least common condition involves urate as an integral part of the urolith as an ammonium salt driven by high ammonium and high urate concentrations in urine. Here, uric acid is one of the perpetrators of the crime. Both known and postulated pathogenesis of these three types of urolithiasis are reviewed and summarized.
尿酸是人类嘌呤代谢的终产物。一个不寻常且尚未得到解释的现象是，由于缺乏降解和肾脏保留，高等灵长类动物的体液中尿酸水平相对较高。高尿酸水平的生理目的仍然是神秘的，但病理生物学负担是由于尿酸的低水溶解度而导致的多种结晶病，如痛风性关节炎和急性尿酸肾病。在尿空间中，由于慢性尿酸和/或尿酸盐沉淀，会出现三种不同的情况。第一种也是最常见的是尿酸尿石症。在这种情况下，尿酸是一种全身性代谢疾病的受害者，其中肾脏的酸负荷增加，同时由于铵排泄缺陷导致尿缓冲能力降低，导致尿酸被滴定到其溶解度较低的质子化对应物尿酸，并形成结石。尿酸是犯罪的无辜旁观者。第二种是高尿酸钙尿石症，其中尿酸通过多种机制促进草酸钙沉淀而具有成石性，这些机制涉及可溶性、胶体和结晶尿酸盐。尿酸是犯罪的始作俑者。第三种也是最不常见的情况是，尿酸作为铵盐的一部分作为结石的一部分存在于尿中，这是由尿液中高铵和高尿酸浓度驱动的。在这里，尿酸是犯罪的共犯之一。综述并总结了这三种尿石症的已知和推测的发病机制。
