Chronic kidney disease (CKD) is inherently an inflammatory condition, which ultimately results in the development of end stage renal disease or cardiovascular events. Low-grade inflammatory diseases such as hypertension and diabetes are leading causes of CKD. Declines in renal function correlate with elevated circulating pro-inflammatory cytokines in patients with these conditions. The inflammasome is an important inflammatory signalling platform that has been associated with low-grade chronic inflammatory diseases. Notably, activation and assembly of the inflammasome causes the auto cleavage of pro-caspase-1 into its active form, which then processes the pro-inflammatory cytokines pro-interleukin (IL)-1β and pro-IL-18 into their active forms. Currently, the nod-like receptor protein 3 (NLRP3) inflammasome has been implicated in the development of CKD in pre-clinical and clinical settings, and the ablation or inhibition of inflammasome components have been shown to be reno-protective in models of CKD. While clinical trials have demonstrated that neutralisation of IL-1β signalling by the drug anakinra lowers inflammation markers in haemodialysis patients, ongoing preclinical studies are showing that this ability to attenuate disease is limited in progressive models of kidney disease. These results suggest a potential predominant role for IL-18 in the development of CKD. This review will discuss the role of the inflammasome and its pro-inflammatory product IL-18 in the development of renal fibrosis and inflammation that contribute to the pathophysiology of CKD. Furthermore, we will examine the potential of the IL-18 signalling axis as an anti-inflammatory target in CKD and its usefulness as diagnostic biomarker to predict acute kidney injury.

慢性肾病 (CKD) 本质上是一种炎症性疾病，最终导致终末期肾病或心血管事件的发展。高血压和糖尿病等低度炎症性疾病是导致 CKD 的主要原因。在患有这些病症的患者中，肾功能下降与循环促炎细胞因子升高相关。炎性体是一种重要的炎症信号平台，与低度慢性炎症性疾病有关。值得注意的是，炎性体的激活和组装导致 pro-caspase-1 自动切割成其活性形式，然后将促炎细胞因子前白细胞介素 (IL)-1β 和 pro-IL-18 加工成它们的活性形式。目前，在临床前和临床环境中，点头样受体蛋白 3 (NLRP3) 炎症小体与 CKD 的发展有关，炎症小体成分的消融或抑制已被证明在 CKD 模型中具有肾脏保护作用。虽然临床试验表明药物阿那白滞素中和 IL-1β 信号可以降低血液透析患者的炎症标志物，但正在进行的临床前研究表明，这种减轻疾病的能力在肾病进行性模型中是有限的。这些结果表明 IL-18 在 CKD 的发展中具有潜在的主导作用。本综述将讨论炎性体及其促炎产物 IL-18 在导致 CKD 病理生理的肾纤维化和炎症发展中的作用。此外，