Mortality among patients with
chronic kidney disease (CKD) is largely a consequence of
cardiovascular disease (CVD) and is a particular concern given the increasing prevalence of CKD. Sterile
inflammation triggered by activation of the innate immune system is an important driver of both CKD and associated CVD. Several endogenous mediators, including
lipoproteins, crystals such as
silica,
urate and
cholesterol crystals, or compounds released from dying cells interact with
pattern recognition receptors expressed on a variety of different cell types, leading to the release of pro-inflammatory
cytokines. Disturbed regulation of the haematopoietic system by damage-associated molecular patterns, or as a consequence of clonal haematopoiesis or trained innate immunity, also contributes to the development of
inflammation. In observational and genetic association studies,
inflammation is linked to the progression of CKD and cardiovascular events. In 2017, the CANTOS trial of
canakinumab provided evidence that inhibiting
inflammation driven by NLRP3-IL-1-IL-6-mediated signalling significantly reduced cardiovascular event rates in individuals with and without CKD. Other approaches to target innate immune pathways are now under investigation for their ability to reduce cardiovascular events and slow
disease progression among patients with
atherosclerosis and stage 3 and 4 CKD. This Review summarizes current understanding of the role of
inflammation in the pathogenesis of CKD and its associated CVD, and how this knowledge may translate into novel
therapeutics.