Artigo Acesso aberto Revisado por pares

Proteomics of CKD progression in the chronic renal insufficiency cohort

2023; Nature Portfolio; Volume: 14; Issue: 1 Linguagem: Inglês

10.1038/s41467-023-41642-7

ISSN

2041-1723

Autores

Ruth F. Dubin, Rajat Deo, Yue Ren, Jianqiao Wang, Zihe Zheng, Haochang Shou, Alan S. Go, Afshin Parsa, James P. Lash, Mahboob Rahman, Chi‐yuan Hsu, Matthew R. Weir, Jing Chen, Amanda H. Anderson, Morgan E. Grams, Aditya Surapaneni, Josef Coresh, Hongzhe Li, Paul L. Kimmel, Ramachandran S. Vasan, Harold I. Feldman, Mark R. Segal, Peter Ganz,

Tópico(s)

Diabetes and associated disorders

Resumo

Abstract Progression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.

Referência(s)