Abstract: SA-PO0281
Mouse Model of CKD with Hyperphosphatemia Develops Lung Calcifications and Dysfunction
Session Information
- Bone and Mineral Metabolism: Basic Research
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 501 Bone and Mineral Metabolism: Basic
Authors
- Fajol, Abul, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Larson-Casey, Jennifer L., Division of Pulmonary, Allergy and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Madison, Matthew C, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Verma, Vivek, Department of Urology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Genschmer, Kristopher R., Division of Pulmonary, Allergy and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Thomas, Madison, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Li, Qing, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Zarjou, Abolfazl, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Gutierrez, Orlando M., The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
- Mitchell, Tanecia, Department of Urology, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Krick, Stefanie, Division of Pulmonary, Allergy and Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama, United States
- Faul, Christian, The University of Alabama at Birmingham Division of Nephrology, Birmingham, Alabama, United States
Background
Elevations in serum phosphate levels (hyperphosphatemia) occur in chronic kidney disease (CKD) and are associated with vascular calcification and mortality. Elevated phosphate can induce osteogenic and inflammatory gene programs in vascular smooth muscle cells and thereby directly cause vascular calcification. While calcifications in the lung have been described in genetic disorders, malignancies and inflammatory conditions, it is unknown whether hyperphosphatemia can induce pulmonary calcifications. In general, the interconnection between CKD and lung disease is not well established. Here, we studied whether a mouse model of CKD with hyperphosphatemia develops lung calcification.
Methods
DBA/2 mice were administered a diet containing adenine (0.2%) and high-phosphate (2.0%) for 8 weeks. Calcifications in the lung and aorta were were visualized by Alizarin red and von Kossa stainings. Calcification events were further characterized by qPCR expression analysis of osteogenic and inflammatory markers. Lung function was determined in anesthetized mice using flexiVent (SCIREQ). Phosphate levels in serum and in isolated tissues were determined by a colorimetric assay. Nanoparticles in the bronchoalveolar lavage (BAL) fluid were quantified by NanoSight Technology and visualized by transmission electron microscopy. Cells in the BAL fluid were analyzed by flow cytometry.
Results
CKD mice developed hyperphosphatemia and severe calcifications in the lung and aorta, which were accompanied by increased expression of osteogenic and inflammatory markers and elevated tissue phosphate content. Pulmonary function was significantly impaired, showing both obstructive and restrictive changes. Increased neutrophil counts and recruited macrophages were evident in the BAL, as well as calcium-containing nanoparticles that displayed a crystal-like morphology. These pathologic alterations were absent in DBA/2 control mice receiving a standard diet.
Conclusion
CKD mice develop pulmonary calcifications that are accompanied by reduced lung function. Future studies in CKD patients are need to determine the clinical relevance of these findings. Therapeutic approaches to lower systemic phosphate levels might protect the lung in CKD patients.
Funding
- NIDDK Support