Kidney Week

Abstract: FR-PO984

A Novel Titratable Pig Model of Mild, Moderate, and Severe CKD

Session Information

• CKD Mechanisms: From Mendel to Mars
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2303 CKD (Non-Dialysis): Mechanisms

Authors

• Uriyanghai, Unimunkh, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Unimunkh Uriyanghai,

• Wai, Christine, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Christine Wai,

• Sidhu, Jasleen, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Jasleen Sidhu,

• Sudarsanam, Vinay A., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Vinay A. Sudarsanam,

• Celdran-Bonafonte, Diego, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Diego Celdran-Bonafonte,

• Arteaga, Eyla C., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Eyla C. Arteaga,

• Lewis, Taylor G., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Taylor G. Lewis,

• Massoud, Nicole D., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Nicole D. Massoud,

• Shipley, Steven, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Steven Shipley,

• Hostetter, Thomas H., The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Thomas H. Hostetter,

• Xi, Gang, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Gang Xi,

• Roy-Chaudhury, Prabir, The University of North Carolina at Chapel Hill Kidney Center, Chapel Hill, North Carolina, United States

Prabir Roy-Chaudhury,

Background

Patients with CKD stages 3-5/ESKD have a very significant cardiovascular (CV) and peripheral vascular morbidity and mortality characterized by a “reverse epidemiology”. Despite the magnitude of the clinical problem there has been minimal investigation into the impact of different levels of uremia on vascular complications (cardiovascular and vascular access) in CKD/ESKD patients. In order to address this unmet translational science need we aimed to surgically induce differing levels of uremia corresponding to CKD stages 3-5 in a pig model.

Methods

Yorkshire Cross pigs underwent a unilateral nephrectomy followed by selective ligation of the arterial tree of the contralateral kidney in order to leave 30% (mild CKD), 15% (moderate CKD) or 7.5% (severe CKD) only of the contralateral kidney with viable perfusion.

Results

Fig 1 describes the initial rise in creatinine followed by a stable creatinine (days 20-30) in the three groups above. Initial data also documents increased levels of known uremic vascular toxins such as indoxyl sulphate and para cresol in the uremic pigs. Importantly, the pigs remained responsive at high creatinine levels (upto 20mg/dL) and did not have significant hyperkalemia.

Conclusion

The described titratable uremic pig model will allow us to (a) describe the concentrations of known uremic vascular toxins such as indoxyl sulphate at different levels of CKD severity (b) perform “omic” analyses on vascular tissue at different levels of CKD severity both prior to and following vascular injury and (c) identify uremia specific pathways of vascular injury that could result in the identification of novel biomarkers and druggable targets for CV risk stratification and future CV therapeutic intervention respectively in CKD patients.

Funding

• Veterans Affairs Support