Effect of elevated serum uric acid on cisplatin-induced acute renal failure
Effect of elevated serum uric acid on cisplatin-induced acute renal failure
复制标题
DOI：
10.1152/ajprenal.00160.2006
复制
发表时间：
2007-01-01
影响因子：
4.2
通讯作者：
Ejaz, A. Ahsan
中科院分区：
文献类型：
--
作者：
Roncal, Carlos A.;Mu, Wei;Ejaz, A. Ahsan
众所周知，显著的高尿酸血症可通过肾内结晶沉积导致急性肾功能衰竭。然而，最近的研究表明，轻度高尿酸血症可能具有血管活性和促炎作用，而不是晶体形成。因此，我们在顺铂诱导的大鼠急性肾功能衰竭模型中测试了轻度高尿酸血症可能加剧肾脏损伤和功能障碍的假设。顺铂应用于正常尿毒症大鼠和高尿酸血症大鼠(后者是通过注射尿酸氧化酶抑制剂氧酸产生的)。第三组应用重组尿酸氧化酶(Rasburicase)来评估降低尿酸对预后的影响。其他对照组包括正常大鼠和未受顺铂损伤的高尿酸血症大鼠。顺铂导致近端小管直肠部(S3)段损伤，并伴有轻度单核细胞浸润。高尿酸血症大鼠表现出明显的肾小管损伤和增殖，巨噬细胞浸润明显增加，单核细胞趋化蛋白-1表达增加。然而，顺铂损伤后正常尿酸血症大鼠和高尿酸血症大鼠的肾功能无明显差异。雷公藤酸酶治疗逆转了炎症变化，减轻了肾小管损伤，改善了肾功能(相对于高尿酸血症组)。各组均未见肾内晶体。这些数据提供了第一个实验证据，表明尿酸在不会导致肾内晶体形成的浓度下，可能会加剧急性肾功能衰竭模型的肾脏损伤。其机制可能与促炎症途径有关，包括趋化因子的表达和白细胞的渗透。
Marked hyperuricemia is known to cause acute renal failure via intrarenal crystal deposition. However, recent studies suggest mild hyperuricemia may have vasoactive and proinflammatory effects independent of crystal formation. We therefore tested the hypothesis that mild hyperuricemia might exacerbate renal injury and dysfunction in a model of cisplatin-induced acute renal failure in the rat. Cisplatin was administered to normouricemic and hyperuricemic rats (the latter generated by administering the urate oxidase inhibitor, oxonic acid). Recombinant urate oxidase (rasburicase) was administered in a third group to assess the effect of lowering uric acid on outcomes. Other control groups include normal rats and hyperuricemic rats without cisplatin-induced injury. Cisplatin induced injury of the pars recta (S3) segment of the proximal tubule in association with a mild monocyte infiltration. Hyperuricemic rats showed significantly greater tubular injury and proliferation with significantly greater macrophage infiltration and increased expression of monocyte chemoattractant protein-1. However, renal function was not different between normouricemic and hyperuricemic rats with cisplatin injury. Treatment with rasburicase reversed the inflammatory changes and lessened tubular injury with an improvement in renal function (relative to the hyperuricemic group). No intrarenal crystals were observed in any groups. These data provide the first experimental evidence that uric acid, at concentrations that do not cause intrarenal crystal formation, may exacerbate renal injury in a model of acute renal failure. The mechanism may relate to a proinflammatory pathway involving chemokine expression with leukocyte infiltration.