Complement Pathway Correlates with Rapid Progression of Type 2 Diabetic Kidney Disease in Korean and American Cohorts

Le résumé fourni par la source

Background: Rapid progression of certain patients with diabetic kidney disease (DKD) remains a threatening issue despite existing treatments. However, their pathophysiological characteristics have not been well defined. This study addresses this gap by examining both Korean and American type 2 DKD cohorts through untargeted and targeted urinary proteomics, respectively. Methods: We conducted untargeted proteomics on urine samples collected at the time of kidney biopsy from Korean patients diagnosed with biopsy-confirmed DKD (SNUH-DN cohort) in the context of type 2 diabetes (n=64) and validated the findings using targeted proteomics on those collected at the time of enrollment in the Chronic Renal Insufficiency Cohort study (n=282, CRIC-T2D cohort). Kidney progression as an outcome was defined as either doubling of serum creatinine, ≥50% decrease in eGFR, or the development of ESKD. For untargeted proteomics, analyses for pathways were employed to identify urinary biomarkers associated with kidney progression. Results: A total of 1,877 proteins were quantified from the patients in SNUH-DN cohort with eGFR of 55 ml/min/1.73m2 (IQR 44–75) and a random uPCR of 3.1g/g (1.7–7.0). The urinary proteins were clustered into two groups, and kidney progression was primarily observed in one group. This group, exhibiting a tendency for rapid kidney progression, had an elevated complement pathway as a proteomic set. When certain complement proteins were measured as a target in the patients from CRIC-T2D cohort with a baseline estimated glomerular rate of 42ml/min/1.73m2 (37–49) and 24-hr urine protein of 0.48g (0.10–1.87), those with a high abundance of complements experienced rapid kidney progression compared to those with low abundance. Conclusion: Urinary proteomic profiling confirms the involvement of the complement pathway in the rapid progression of type 2 DKD. The results will serve as the basis for studies aimed at manipulating relevant complements for the treatment of patients with type 2 DKD. Funding: Clinical Revenue Support(A) UMAP of untargeted proteomics. (B) Adjusted survival curves for kidney progression according to clustering in SNUH-DN cohort.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.