Stage II of Chronic Kidney Disease—A Tipping Point in Disease Progression?

Abstract

Chronic kidney disease (CKD) is the progressive loss of renal function. Although advances have been made in understanding the progression of CKD, key molecular events in complex pathophysiological mechanisms that mark each stage of renal failure remain largely unknown. Changes in plasma protein profiles in different disease stages are important for identification of early diagnostic markers and potential therapeutic targets. The goal of this study was to determine the molecular profile of each CKD stage (from 1 to 5), aiming to specifically point out markedly expressed or downregulated proteins. We performed a cross-sectional shotgun-proteomic study of pooled plasma across CKD stages and compared them to healthy controls. After sample pooling and heparin-column purification we analysed proteomes from healthy to CKD stage 1 through 5 participants’ plasma by liquid-chromatography/mass-spectrometry. We identified 453 proteins across all study groups. Our results indicate that key events, which may later affect the course of disease progression and the overall pathophysiological background, are most pronounced in CKD stage 2, with an emphasis on inflammation, lipoprotein metabolism, angiogenesis and tissue regeneration. We hypothesize that CKD stage 2 is the tipping point in disease progression and a suitable point in disease course for the development of therapeutic solutions.

Keywords

• angiogenesis
• chronic kidney disease
• inflammation
• proteomics
• tissue regeneration