Oxalate, inflammasome, and progression of kidney disease.
Oxalate, inflammasome, and progression of kidney disease.
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DOI：
10.1097/mnh.0000000000000229
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发表时间：
2016-07
影响因子：
3.2
通讯作者：
Knauf F
中科院分区：
文献类型：
--
作者：
Ermer T;Eckardt KU;Aronson PS;Knauf F
草酸盐是通过肾脏排泄的代谢终产物。无论是原发性还是肠源性高尿酸尿，过量的尿草酸盐可导致草酸盐在肾脏沉积。草酸盐结晶与肾脏炎症、纤维化和进行性肾衰竭有关。长期以来，人们一直知道，随着肾小球滤过率（GFR）在慢性肾病（CKD）中降低，血浆草酸盐显著升高。总之，这些发现提高了CKD患者血浆草酸盐升高可能促进肾脏炎症和CKD更快进展的可能性，而与原发病因无关。炎性小体最近已被确定在尿酸盐诱导的肾脏炎症中起关键作用。草酸盐晶体已显示激活核苷酸结合结构域、富含亮氨酸的重复炎性体3（也称为NALP 3、NLRP 3或cryopyrin），导致白细胞介素-1 β的释放和巨噬细胞浸润。小鼠中炎性体蛋白的缺失可防止尿酸盐诱导的肾脏炎症和进行性肾衰竭。本文综述的研究结果扩展了我们对血浆草酸水平升高导致炎性小体激活的相关性的理解。我们认为，抑制草酸盐诱导的炎性体激活或降低血浆草酸盐可以预防或减轻慢性肾病的进行性肾损伤，并值得进行临床试验。
Oxalate is an end product of metabolism excreted via the kidney. Excess urinary oxalate, whether from primary or enteric hyperoxaluria, can lead to oxalate deposition in the kidney. Oxalate crystals are associated with renal inflammation, fibrosis and progressive renal failure. It has long been known that as glomerular filtration rate (GFR) becomes reduced in chronic kidney disease (CKD), there is striking elevation of plasma oxalate. Taken together, these findings raise the possibility that elevation of plasma oxalate in CKD may promote renal inflammation and more rapid progression of CKD independent of primary etiology. The inflammasome has recently been identified to play a critical role in oxalate-induced renal inflammation. Oxalate crystals have been shown to activate the nucleotide-binding domain, leucine-rich repeat inflammasome 3 (also known as NALP3, NLRP3 or cryopyrin), resulting in release of Interleukin-1β and macrophage infiltration. Deletion of inflammasome proteins in mice protects from oxalate-induced renal inflammation and progressive renal failure. The findings reviewed in this article expand our understanding of the relevance of elevated plasma oxalate levels leading to inflammasome activation. We propose that inhibiting oxalate-induced inflammasome activation, or lowering plasma oxalate, may prevent or mitigate progressive renal damage in CKD, and warrants clinical trials.