Visceral adipose tissue is associated with changes in leptin, FGF-23 and vitamin D metabolism in chronic kidney disease

Leptin, a hormone produced by adipose tissue, stimulates bone production of FGF-23 in pre-clinical studies and thus may impact vitamin D metabolism. We investigated the association between longitudinal changes in visceral (VAT) and subcutaneous adipose tissue (SAT) and vitamin D metabolism in patients receiving hemodialysis. This cohort study of clinical trial participants included adult patients receiving hemodialysis who were not taking active vitamin D therapy at baseline (n=30) and 1 year (n=26). VAT and SAT cross-sectional area was measured by MDCT scanner and SliceOMatic software. Vitamin D metabolites were measured with mass spectroscopy and expressed as vitamin D metabolite ratios (VMR). FGF-23, leptin and adiponectin were measured by ELISA. Spearman correlation and Wilcoxan rank-sum tests were used to evaluate baseline and relative change variables. Linear regression was used to evaluate the relationship between changes in FGF-23 and leptin. The progression towards increased fat in the visceral area (VSR) was associated with an increase in FGF-23 and leptin and a decline in the ratio between the active vitamin D hormone, 1,25(OH)2D3, and the 25(OH)D3 precursor molecule. The relative change in leptin as well as the leptin to adiponectin ratio was associated with the change in FGF-23 controlling for baseline FGF-23 and PTH. Adipose tissue may contribute to altered vitamin D metabolism. This effect appeared primarily related to visceral adipose tissue and the progression towards increased fat in the viscera. Whether the changes in vitamin D metabolism are directly related to the observed changes in FGF-23 and leptin, or a local effect within adipocytes, requires further study. Consideration of body composition may be one step towards personalizing the care and treatment of CKD-associated mineral and bone disorders based on individual characteristics.