Kidney Week

Abstract: TH-PO0258

Urinary Extracellular Vesicle Proteomics Reveals Inflammatory and Early Fibrotic Kidney Signatures in People with HIV

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

• Fisher, Molly, Albert Einstein College of Medicine, New York, New York, United States

Molly Fisher, DO, MS, FASN

• Chaudhry, Sahir K., Albert Einstein College of Medicine, New York, New York, United States

Sahir K. Chaudhry, MS

• Dash, Surjya Narayan, University of Virginia, Charlottesville, Virginia, United States

Surjya Narayan Dash, PhD

• Abramowitz, Matthew K., Albert Einstein College of Medicine, New York, New York, United States

Matthew K. Abramowitz, MD, MS, FASN

• Erdbruegger, Uta, University of Virginia, Charlottesville, Virginia, United States

Uta Erdbruegger, MD

• Ross, Michael J., Albert Einstein College of Medicine, New York, New York, United States

Michael J. Ross, MD, FASN

Background

People with HIV (PWH) have chronic immune activation despite viral suppression and increased kidney disease risk. Urinary extracellular vesicles (uEV) released from living kidney cells contain cargo from their parent cell, providing a noninvasive window into kidney biology. We hypothesized that immune activation contributes to subclinical kidney injury detectable in the uEV proteome.

Methods

uEVs were isolated from 10 virally suppressed PWH and 9 controls without HIV, all with eGFR >60 ml/min/1.73m2. EV enrichment was confirmed by transmission electron microscopy and western blot for EV proteins. Liquid chromatography tandem mass spectrometry identified and quantified 562 proteins. Differential abundance was tested by Welch t-test (significance: absolute log2 fold change >1.5, p<0.05). Canonical pathway and upstream regulator analyses were performed. Spearman's rank assessed clinical correlations.

Results

54 proteins were elevated and 5 were reduced in HIV+ uEVs (p<0.05) (Figure, panel A). The dominant signature was inflammatory and acute phase signaling, including neutrophil degranulation (p<0.0001), followed by LXR/RXR activation, acute phase response signaling (LRG1, SERPINA1, ITIH4, CP, TF), and complement cascade (C4B, MASP2). Kidney tubular epithelial proteins (LRP2, SLC12A1, ATP1A1); and fibrosis-associated proteins (LTBP2, VIM, MXRA8, OGN) were also elevated, alongside enrichment of extracellular matrix organization and pre-fibrotic pathways. Upstream regulator analysis predicted activation of STAT3, interleukin-6, and lipopolysaccharide, linking immune activation to the observed uEV proteome. LRG1, the most differentially abundant protein (log2 fold change +5.0, p<0.0001), inversely correlated with CD4 count (r= -0.64, p=0.048) (Figure, panel B).

Conclusion

The uEV proteome in virally suppressed PWH revealed a prominent inflammatory signature with early fibrotic remodeling, despite preserved kidney function. These findings suggest a link between immune activation and subclinical kidney injury and highlight uEVs as a promising noninvasive platform for early detection and mechanistic insight into HIV-related kidney injury.

Funding

• NIDDK Support