Abstract: SA-PO1106
Inflammatory Proteome Associated with Fatigue in Nondialysis-Dependent CKD
Session Information
- Geriatric Nephrology
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Geriatric Nephrology
- 1300 Geriatric Nephrology
Authors
- Duran, Sally, Albert Einstein College of Medicine, Bronx, New York, United States
- Alzyood, Laith, Albert Einstein College of Medicine, Bronx, New York, United States
- Islam, Saisha, Albert Einstein College of Medicine, Bronx, New York, United States
- Paredes, William, Albert Einstein College of Medicine, Bronx, New York, United States
- Abramowitz, Matthew K., Albert Einstein College of Medicine, Bronx, New York, United States
Background
People living with CKD experience high symptom burden and fatigue. In patients with ESKD, studies have investigated associations between inflammatory markers and patient-reported pain, fatigue, and depression. However, less is known about the role of inflammation in symptom burden and fatigue in non-dialysis dependent CKD patients, and deep proteomic profiling is lacking
Methods
We measured 250 inflammation and immune response plasma proteins using Nucleic acid Linked Immuno-Sandwich Assay (NULISA™, Alamar Biosciences) in 76 participants from 2 prospective cohorts of adults with CKD stages 4 and 5 and healthy age-matched controls. Fatigue and symptom burden were quantified using PROMIS Fatigue 7a and Renal Palliative Care Outcome Scale (POS) respectively. We defined fatigue as PROMIS T-score ≥55 and high symptom burden as POS > 6. Logistic regression adjusted for age and sex was used to test associations with high fatigue and symptom burden accounting for multiple comparisons at an FDR q-value <0.05.
Results
The mean age was 63±9 years, 44% were women, 58% identified as Black, and 16% Hispanic. PROMIS and POS scores were worse in CKD patients (n=49) compared with controls (n=27): 52±8 vs 42±7, and 6 (IQR 2-11) vs 3 (IQR 0-6) respectively. Among the 250 proteins profiled, 51 were significantly associated with fatigue with log2 fold change>0.5; all were overexpressed. Top differentially expressed pathways included cytokine signaling, IL-17 signaling, and macrophage classical activation. No proteins were associated with symptom burden; in an exploratory analysis using q<0.1, 5 proteins were significant and all overlapped with the fatigue-associated signature (HAVCR1, LCN2, CCL16, TSLP and TREM1).
Conclusion
Using NULISASeq, which is 10,000-fold more sensitive than proximity ligation assays, revealed a potential inflammatory protein signature of CKD-associated fatigue. Furthermore, specific proteins were shown to be overexpressed in both high fatigue and high symptom burden. These findings merit further investigation and may serve as a guide for biomarker discovery.
Funding
- NIDDK Support