Fibroblast growth factor 23 and disordered vitamin D metabolism in chronic kidney disease: updating the "trade-off" hypothesis.
The discovery of fibroblast growth factor 23 (FGF23) has clarified much of our understanding of abnormalities in phosphorus and vitamin D metabolism in chronic kidney disease (CKD). FGF23 is a bone-derived hormone that promotes phosphaturia and decreases the synthesis of 1,25-dihydroxyvitamin D (1,25(OH)(2)D). The primary systemic stimuli of FGF23 secretion are increased 1,25(OH)(2)D levels and increased dietary phosphorus intake. In kidney failure, FGF23 levels increase early and steadily rise with progression of kidney disease, likely as an appropriate physiologic adaptation to maintain normal phosphorus balance by helping to augment urinary phosphate excretion in conjunction with increased parathyroid hormone levels and by decreasing gut phosphorus absorption through decreased 1,25(OH)(2)D. In the long term, this compensation may become maladaptive by causing a progressive decline in 1,25(OH)(2)D levels with attendant consequences such as secondary hyperparathyroidism. Moreover, excess FGF23 levels have been independently linked with cardiovascular disease and mortality, suggesting that chronically elevated FGF23 levels may directly contribute to adverse CKD outcomes. Together, these findings have sparked increased interest in elucidating the potential interconnections between dietary phosphorus intake, FGF23, and clinical outcomes in patients with CKD. In addition, given that treatment with activated vitamin D compounds stimulates FGF23, these data have raised important new questions about the optimal use of activated vitamin D compounds in the management of bone and mineral disorders in CKD.
Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USA. ogutierrez2@med.miami.edu
Orlando M
OM
Gutiérrez
D000818:Animals; D002908:Chronic Disease; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000209:etiology / Q000378:metabolism; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D010281:Parathyroid Hormone / Q000378:metabolism; D016226:Phosphorus, Dietary / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism* / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D014815:Vitamins / Q000627:therapeutic use
C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D016226:Phosphorus, Dietary; D014815:Vitamins; D014807:Vitamin D; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23