Related Experiment Video
Updated: Sep 15, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Complement Proteins Identify Rapidly Progressive Diabetic Kidney Disease
Donghwan Yun1,2, Sohyun Bae1, Yuqian Gao3
1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Introduction:
Mechanisms underlying diabetic kidney disease (DKD) progression remain incompletely understood. This study used untargeted and targeted mass spectrometry-based proteomics in 2 independent cohorts to capture rapidly progressive DKD.
Methods:
We conducted untargeted and targeted mass spectrometry on urine samples from Korean patients with type 2 diabetes and biopsy-confirmed diabetic nephropathy (SNUH-DN cohort; n = 64) and a DKD subgroup of the Chronic Renal Insufficiency Cohort (CRIC-T2D; n = 282), respectively. Urine proteins associated with kidney disease progression (doubling of serum creatinine, ≥ 50% decrease in estimated glomerular filtration rates [eGFRs], or progression to end-stage kidney disease[ESKD]) were identified after adjusting for eGFR, proteinuria, and other clinical variables.
Results:
In the SNUH-DN patients, urine proteins clustered into 2 groups, with cluster 1 exhibiting a 4.6-fold higher hazard of disease progression (95% confidence interval [CI]: 1.9-11.5) than cluster 0. Proteins in cluster 1 mapped to 10 pathways, 4 of the top 5 being complement-related. A high complement score, derived from urine complement protein abundance, correlated with histopathologic features of DKD and conferred a 2.4-fold greater hazard of disease progression (95% CI: 1.0-5.4) than a low complement score. In CRIC-T2D, targeted mass spectrometry similarly confirmed that complement score stratified patients into rapid and slow DKD progression groups. In both cohorts, complement score exhibited a linear association with disease progression.
Conclusion:
The strong association between complement activation and rapid DKD progression highlights the need to explore complement inhibition as a potential therapeutic strategy for DKD.
Related Concept Videos
Chronic Kidney Disease I: Introduction
Renal Corpuscle
Glomerulus: Structure and Function
The glomerulus is a tiny, intricate network of capillaries located at the beginning of the nephron. It's enveloped by the Bowman's capsule and receives its blood supply from an afferent arteriole, which divides into numerous...
Chronic Kidney Disease III: Interprofessional Care
Acute Kidney Injury IV: Diagnostic Studies and Prevention
Nephrotic Syndrome II : Assessment and Medical Management
Acute Kidney Injury I: Introduction

