Fibroblast growth factor 23 and acute kidney injury

Fibroblast growth factor 23 (FGF23), which is produced in bone, participates in the maintenance of phosphate metabolism and can serve as a biomarker for adverse cardiovascular outcomes in patients with chronic kidney disease and end-stage renal disease. Circulating FGF23 rapidly increases after acute kidney injury (AKI), preceding other known markers such as neutrophil gelatinase-associated lipocalin and serum creatinine. The increase in FGF23 in AKI appears to be independent of parathyroid hormone, vitamin D signaling pathways, and dietary phosphate. The potential mechanisms include: (1) increased production of FGF23 in the bone by yet-to-be-identified factors; (2) ectopic production of FGF23 by injured renal tubules; and (3) decreased renal clearance of circulating FGF23. Circulating FGF23 determined by intact FGF23 enzyme-linked immunosorbent assay (ELISA) is a more reliable biomarker of AKI than FGF23 C-terminal ELISA (a mixed readout of C-terminal fragment and intact FGF23). Given that FGF23 can be ectopically expressed in differentiated renal tubules and iron modulates FGF23 metabolism, an effect of iron on FGF23 expression in renal tubules is conceivable but remains to be confirmed. More clinical and experimental studies are required to validate the use of circulating FGF23 as a biomarker for the early identification of AKI and prediction of short- and long-term adverse outcomes post-AKI. More importantly, the biologic effect of increased FGF23 in AKI needs to be defined.