Kidney Week

Abstract: SA-PO0600

Comprehensive Plasma Proteomic Profiling Reveals Molecular Signatures and Functional Alterations in ADPKD

Session Information

• Cystic Kidney Diseases: Clinical Research
  November 08, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Monogenic Kidney Diseases

Authors

• Ali, Hamad, Kuwait University Health Sciences Center, Safat, Kuwait

Hamad Ali, MS, PhD

• Abu-Farha, Mohamed, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Mohamed Abu-Farha, PhD

• Bahbahani, Yousif, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Yousif Bahbahani, MBChB

• Bahbahani, Hamad Mahdi, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Hamad Mahdi Bahbahani, MD, MBChB

• Ayoub, Medhat N., ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Medhat N. Ayoub, MD, PhD

• Alsharhan, Loulwa, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Loulwa Alsharhan, MBChB

• Almutawa, Sarah F A M A, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Sarah F A M A Almutawa, MD

• Almomen, Mohammad, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Mohammad Almomen, MD

• Al Rajab, Heba, ADPKD National Clinic, Mubarak Al-Kabeer Hospital, Kuwait, Kuwait

Heba Al Rajab, MD

• Abubaker, Jehad, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait

Jehad Abubaker, MSc, PhD

Background

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a prevalent hereditary nephropathy characterized by progressive renal cyst formation and systemic dysfunction. Despite its clinical burden, early diagnosis and biomarker-based monitoring remain limited. Here, we employed high-resolution mass spectrometry to perform an in-depth plasma proteomic analysis across healthy individuals and ADPKD groups.

Methods

This pilot cross-sectional study analyzed plasma from healthy individuals (n=14) and ADPKD patients (n=8) using DIA (Bruker timsTOF Pro) and DDA (Thermo Q-Exactive HF). Proteins were identified via Spectronaut and Proteome Discoverer. Multivariate analyses (PCA, PLS-DA, OPLS-DA), functional annotation (DAVID, Metascape, WebGestalt), and PPI networks (GeneMANIA) were performed. Biomarker selection used random forest with ROC evaluation.

Results

We identified distinct plasma proteomic signatures in ADPKD patients compared to healthy controls. Differential expression analysis revealed significant upregulation (, of complement cascade and extracellular matrix remodeling proteins (including HCF1, SBP1, TPM3, AOC3) and significant downregulation (, 1) of immune and coagulation factors (including, FA9, IGHA1, ENOA). Functional enrichment highlighted dysregulation in pathways related to PI3K/AKT signaling, GPCR signaling, platelet activation, and morphogenesis. Random forest modeling identified top discriminatory proteins including HCFC1, HBA, MSLN, and TPM3, achieving high classification accuracy and diagnostic potential. Network analysis further clustered these markers into biologically relevant modules, suggesting perturbed signaling, cytoskeletal organization, and immune response in ADPKD.

Conclusion

This study presents a comprehensive plasma proteomic landscape in ADPKD, revealing candidate diagnostic biomarkers and key dysregulated pathways. These findings contribute to improved understanding of disease mechanisms and support future efforts toward biomarker-driven diagnostics and targeted therapies in ADPKD.

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025y3e824cd