Schunk S, Hermann J, Sarakpi T, et al. - Higher guanidinylated apolipoprotein C3 (gApoC3) plasma levels (as ascertained via mass spectrometry) in chronic kidney diseases (CKD) patients were related to elevated mortality as well as with renal and cardiovascular events. ApoC3 guanidinylation was identified as a novel pathogenic mechanism in CKD and CKD-linked vascular injury, suggesting gApoC3 as a potential treatment target.

• As recently discovered, ApoC3 activates the NOD-like receptor protein-3 inflammasome in human monocytes via an alternative pathway, in turn, resulting in sterile systemic inflammation.

• This study involved CKD patients, healthy individuals, experimental models and in vitro exploration.

• CKD patients showed significant posttranslational gApoC3.

• Mechanistically, guanidinylation of ApoC3 was brought about by guanidine and urea.

• A CKD mouse model (mice fed an adenine-rich diet) showed accumulation of gApoC3 in kidneys and plasma.

• gApoC3 augmented the proinflammatory impacts of ApoC3 of monocytes in vitro.

• Humanized mice models revealed gApoC3 as a promoter of kidney tissue fibrosis and an obstacle for vascular regeneration.