Kidney Week

Abstract: TH-PO153

Expansion of Visceral Adipose Tissue over 12 Months Is Associated with Changes in Leptin and Fibroblast Growth Factor 23 (FGF-23) and Alterations in Vitamin D Metabolism in Patients with ESKD

Session Information

• CKD-MBD: Clinical
  October 24, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Holden, Rachel M., Queen's University, Kingston, Ontario, Canada

Rachel M. Holden, MD

• Norman, Patrick Alexander, Kingston Health Sciences Centre, Kingston, Ontario, Canada

Patrick Alexander Norman, MS

• Kaufmann, Martin, Queen's University, Kingston, Ontario, Canada

Martin Kaufmann, PhD

• Turner, Mandy E., Harvard University, Cambridge, Massachusetts, United States

Mandy E. Turner, PhD

• Moist, Louise M., Western University, London, Ontario, Canada

Louise M. Moist, MD, MS, MSc

• Zimmerman, Deborah Lynn, University of Ottawa, Ottawa, Ontario, Canada

Deborah Lynn Zimmerman, MD

• Ward, Emilie C., Queen's University, Kingston, Ontario, Canada

Emilie C. Ward

• Petkovich, Martin P., Queen's University, Kingston, Ontario, Canada

Martin P. Petkovich, PhD

• Adams, Michael A., Queen's University, Kingston, Ontario, Canada

Michael A. Adams, PhD

• Mourtzakis, Marina, University of Waterloo, Waterloo, Ontario, Canada

Marina Mourtzakis, PhD

Background

Visceral adipose tissue (VAT) is hormonally active. Leptin, produced by adipocytes, is a cytokine-like hormone that is increased with obesity. Leptin stimulates FGF-23 expression in bone and decreases kidney expression of CYP27B1 in leptin-deficient mice.The objective was to examine the relationship between visceral and subcutaneous adipose tissue and changes over 12 months with leptin, FGF-23, and vitamin D metabolism through assessment of vitamin D metabolite (VMR) ratios of 25(OH)₂D₃ and 1,25(OH)₂D₃ in patients with ESKD.

Methods

Visceral (VAT) and subcutaneous (SAT) adipose tissue cross sectional area (CSA) was assessed by computed tomography at the third lumbar vertebra at baseline and 12 months in hemodialysis patients. Serum vitamin D metabolites were measured by LC-MS/MS and leptin and iFGF-23 were measured by ELISA at baseline and 12 months.

Results

There were 28 participants, 61% with diabetes. At baseline, VAT CSA was associated with higher 1,24,25(OH)₃D₃:1,25(OH)₂D₃ VMR with (r=0.43, p=0.04) and without (r=0.46, p=0.02) adjustment for iFGF-23. Increase in VAT was significantly associated with increase in leptin (r=0.6, p<0.001) and iFGF-23 (r=0.42, p<0.05), as well as increases in the 25(OH)D₃:1,25(OH)₂D₃ VMR (r=0.5, p<0.05) and 1,24,25(OH)₃D₃:1,25(OH)₂D₃ VMR (r=0.5, p<0.05). Participants with an increase in VAT over 12 months (n=17) had significantly greater percent increase in leptin (22.4 [-33.0, 113.3]) and FGF-23 (94.8[26.4,208.9]) compared to those where VAT decreased (n=10) (-54.8 [-58.2, 11.1], p=0.03 for leptin) and -3.0[-31.7, 68.9], p=0.02 for FGF-23. In a linear regression model using log-transformed variables, a 10% increase in the change leptin was associated with a 1.9% increase in the change in FGF-23 (p=0.035) after adjustment for baseline FGF-23 and PTH. In contrast to VAT, SAT CSA was not associated with any VMR at baseline and there was no difference in leptin, FGF-23 or in any VMR between participants who gained SAT versus those where SAT decreased.

Conclusion

VAT may contribute to calcitriol deficiency in patients with ESKD. Expanding VAT appears to enhance FGF-23 regulation of vitamin D metabolism possibly mediated by leptin.

Funding

• Government Support – Non-U.S.