The following is a summary of “Association of Integrated Proteomic and Metabolomic Modules with Risk of Kidney Disease Progression,” published in the April 2024 issue of Nephrology by Schlosser et al.
Researchers conducted a prospective study analyzing the roles of proteins and metabolites in biological functions that are frequently interconnected through enzymatic or transport processes.
They used an integrated analysis of 4,091 proteins and 630 metabolites in chronic renal insufficiency cohort study from 1,708 people with chronic kidney issues and followed them for 9.5 years, with 537 events. An unsupervised clustering method integrated proteins and metabolites, and associations between clusters and CKD progression and kidney failure were assessed using Cox proportional hazards models. Associations were identified in a discovery sample (random two-thirds, n=1139) and then evaluated in a replication sample (one-third, n=569).
The results showed that 139 groups of proteins and metabolites were identified and represented by their principal components. Modules and principal components loadings were projected in another group where the same network structure was identified. Two modules, made up of 236 proteins and 82 metabolites, were linked to worsening kidney issues and failures in both discovery sets of people. Researchers also found certain gene activities that were common in both groups, like transmembrane-ephrin receptor activity (OR 13.2, P= 5.5×10-5). A module containing CRIM1 and NPNT expressed in podocytes demonstrated powerful associations with kidney failure (P=2.6×10-5).
Investigators concluded that combining the proteome and metabolome can uncover critical functions relevant to kidney disease pathophysiology.
Source: journals.lww.com/jasn/abstract/9900/integrated_proteomic_and_metabolomic_modules.281.aspx