Abstract: FR-PO0525
Urinary Proteome, Integrated Analyses, and Kidney Disease Progression in Type 1 Diabetes
Session Information
- CKM: Clinical - Trials, Epidemiology, and Biomarkers
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 602 Cardiovascular-Kidney-Metabolic Health: Clinical
Authors
- Md Dom, Zaipul, Joslin Diabetes Center, Boston, Massachusetts, United States
- Tracy, Maria I., Joslin Diabetes Center, Boston, Massachusetts, United States
- Abedini, Amin, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Becerra, Daniel Perez, Joslin Diabetes Center, Boston, Massachusetts, United States
- Keum, Youngshin, Joslin Diabetes Center, Boston, Massachusetts, United States
- Susztak, Katalin, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Niewczas, Monika A., Joslin Diabetes Center, Boston, Massachusetts, United States
Background
Patients with T1D and diabetic kidney disease (DKD) remain in dire need of clinical advancements. High-throughput proteomics in biofluids shall capture determinants of disease progression beyond those reflected by albuminuria.
Methods
Our prospective study included Joslin Kidney Study participants with T1D and advanced DKD followed for 1059 person-years. Using aptamer technology, we performed urinary proteomics at baseline and longitudinally in a subset. The top urinary proteins were interrogated in kidney tissue proteomics and scRNA-seq datasets.
Results
From among 1,305 proteins measured, the top proteins associated with DKD progression included: (CCL14, CXCL7, C2, C5a, IGFBP-4, SMOC1 among others) representing chemokine and complement involvement, with other components of maladaptive inflammation, fibrosis, vascular injury and insulin growth factor signaling. The hazard ratio, HR (95% CI) for CCL14 was 4.28 (3.14-5.83); Bonferroni P < 10-16, Fig.1A. We also identified 6 proteins associated with DKD progression in the presence of hyperglycemia (ARG1, BCL6, GM-CSF, among others). HR (95%CI) for ARG1 in the presence of HbA1 > 8.5% was 2.94 (2.08-4.15), and it was 1.77 (1.22-2.57) with HbA1c below; Fig.1B. Longitudinal analyses revealed highly dynamic trajectories, at least partially uncoupled from albuminuria (median percent change for CCL14 over time was: +221% and it was: +73% for albuminuria). Integrated omics analyses revealed an increased kidney expression in CKD/DKD of select molecules (CCL14 in endothelium; IGFBP-4 in endothelium, tubules and podocytes; FABPE in macrophages and endothelium).
Conclusion
Urinary proteomics identified proteins strongly associated with kidney disease progression in T1D. Omics integration revealed partial concordance and pointed to relevant cellular sources. These findings suggest that the urinary proteome captures biologically meaningful pathways of DKD progression.
Funding
- Other NIH Support