Kidney Week

Abstract: TH-PO0171

Plasma Metabolomic Profiling Identifies Distinct Lipid and Energy-Metabolism Signatures in ADPKD

Session Information

• ADPKD and Cystic Kidney Disease - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)

Authors

• Almomen, Mohammad, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Mohammad Almomen, MD

• Ayoub, Medhat N., ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Medhat N. Ayoub, MD, PhD

• Bahbahani, Yousif, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Yousif Bahbahani, MBChB

• Al Rajab, Heba, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Heba Al Rajab, MD

• Bahbahani, Hamad Mahdi, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Hamad Mahdi Bahbahani, MD, MBChB

• Almutawa, Sarah F A M A, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Sarah F A M A Almutawa, MD

• Almutar, Sara, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Sara Almutar, MD

• Mohammad, Anwar, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait

Anwar Mohammad, MSc, PhD

• Malik, Mohammad Zubbair, Dasman Diabetes Institute, Kuwait City, Al Asimah Governate, Kuwait

Mohammad Zubbair Malik, PhD

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

Jehad Abubaker, MSc, PhD

• Abu-Farha, Mohamed, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Mohamed Abu-Farha, PhD

• Ali, Hamad, ADPKD National Clinic, Mubarak Al Kabeer Hospital, Ministry of Health, Jabriya, Kuwait

Hamad Ali, MS, PhD

Group or Team Name

• ADPKD National Clinic of Kuwait

Background

Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited kidney disorder characterized by progressive cyst growth, kidney enlargement, and eventual loss of kidney function. Beyond its genetic basis, ADPKD is increasingly recognized as a metabolically active disease, but circulating metabolic signatures associated with ADPKD remain incompletely defined. We performed untargeted plasma metabolomics to identify metabolites that distinguish ADPKD patients from healthy controls.

Methods

Plasma samples from 31 ADPKD patients and 31 healthy controls were analyzed using untargeted gas chromatography–time-of-flight mass spectrometry. Metabolite features were normalized, log2-transformed, Pareto-scaled, and analyzed using principal component analysis, differential abundance testing, metabolite set enrichment analysis, and pathway analysis.

Results

ADPKD patients showed a distinct plasma metabolomic profile compared with healthy controls. Principal component analysis demonstrated clear group separation, with PC1 explaining 31.1% and PC2 explaining 9.9% of total variance. Differential metabolite analysis revealed broad dysregulation of lipid-related metabolites, including acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, sphingomyelins, triglycerides, and diacylglycerols. Enrichment analyses highlighted disruption of glucose metabolism, amino-acid metabolism, fatty-acid and mitochondrial metabolism, phospholipid metabolism, and bile-acid–related pathways. Biological-process enrichment implicated lipid and organic acid transport, mitochondrial function, oxidative metabolism, and inflammatory/metabolic stress pathways. Random Forest analysis identified LPC(14:0), LPC(18:1), SM(40:4), PC(42:7), PC(40:7), PC(40:8), DG-O(36:4), LPC(18:0), PC-O(36:1), TG(53:3), PC(36:6), AC(9:0), AC(16:OH), PC(38:5), and PC-O(40:8) as the top metabolites discriminating ADPKD from controls.

Conclusion

ADPKD is associated with a circulating metabolomic signature dominated by altered lipid handling, mitochondrial energy metabolism, and membrane phospholipid remodeling. These findings support the concept that ADPKD involves systemic metabolic reprogramming beyond structural cystic kidney disease. The identified metabolites may serve as candidate biomarkers for disease stratification and provide mechanistic insight into pathways relevant to ADPKD progression.

Acknowledgment

This work was funded by the KFAS research fund (PR17-13MM-07, to H.A.)