Abstract: TH-PO0234
Development of CKD of Unknown Etiology After AKI: Use of Serum Proteomics to Distinguish Disease Progression from Nonprogression
Session Information
- CKD: Mechanisms of Injury and Fibrosis - 1
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Raja, Mohummad Hassan Raza, Duke University School of Medicine, Durham, North Carolina, United States
- Strasma, Anna, Duke University School of Medicine, Durham, North Carolina, United States
- Johnson, Dylan, National Institute of Environmental Health Sciences, Durham, North Carolina, United States
- Watts, Jason A., National Institute of Environmental Health Sciences, Durham, North Carolina, United States
- Fischer, Rebecca S.B., Texas A&M University, College Station, Texas, United States
- Foley, Julie F., National Institute of Environmental Health Sciences, Durham, North Carolina, United States
Background
Recurrent acute kidney injury (AKI) has been proposed as a precursor to chronic kidney disease of unknown etiology (CKDu), yet biomarkers predicting progression remain undefined. We used serum proteomics to identify biomarkers associated with progression from AKI to CKDu.
Methods
Serum samples from 170 Nicaraguan sugarcane workers presenting with AKI were analyzed. Participants were classified as CKDu progressors (CKDPs; n=63) or non-progressors (CKDNPs; n=107) based on longitudinal surveillance data. Using the Olink proteomics platform, we analyzed 2,751 proteins at the time of AKI. Differentially abundant proteins (DAPs) were identified using a cutoff of p=0.10 & pathway analysis was performed. Findings were compared with known AKI/CKD biomarkers.
Results
There were 110 (4%) DAPs between CKDPs & CKDNPs, with 50 higher & 60 lower. DAPs higher in CKDPs included PTH (3.5-fold; p=0.01), PLRP2 (2.9-fold; p=0.06), VWC2 (2.2-fold; p<0.01), ANKRA2 (2.2-fold; p=0.09) & OGN (1.8-fold; p=0.03). DAPs lower in CKDPs included CALB1 (4.4-fold; p<0.01), LIF (2.2-fold; p=0.1), IL1RL1 (2.1-fold; p<0.01) & UMOD (1.9-fold; p<0.01). Of 37 known AKI/CKD biomarkers evaluated, CD40, NPY, PEDF & SMOC2 were higher in CKDPs while iLL1, UMOD, HGF & PARP1 were lower. Ingenuity Pathway analysis of all DAPs revealed depression of the mitochondrial protein import pathway in CKDPs.
Conclusion
Distinct serum proteomic profiles were identified in patients with AKI who developed CKDu. DAPs involved in fibrosis, tubular protection, inflammation, cellular signaling & mitochondrial function suggest biologic divergence occurs early in this disease process. These candidate biomarkers & their relevant pathways may improve understanding of CKDu pathogenesis & aid future disease prognostic models.
Acknowledgment
This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. The contributions of the NIH author(s) are considered Works of the United States Government. The findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services.
DAPS that were significantly different in CKDPs relative to CKDNPs
Funding
- Other NIH Support