Dipstick 2272 floor profiler
( 1) Late CKD is considered a state of secondary FGF-23 excess as phosphate elevation occurs along with disruption of the PTH, Vitamin D 3, and calcium signaling axis. These findings do not preclude that altered mineral availability or anemia can later modulate FGF-23 levels, but find that in early CKD they are not the driving stimulus for the initial upregulation of FGF-23.ĭuring late Chronic Kidney Disease (CKD) phosphate homeostasis is disrupted. We conclude that early CKD resembles a situation of primary FGF-23 excess mediated by inflammation. Furthermore, neutralizing antibody to IL-1β blocked FGF-23 expression in both our congenital model of CKD and a second nephrotoxic serum-mediated model. IL-1β’s ability to induce FGF-23 was confirmed on bone chips in culture, and within mice in vivo. Instead, production of the inflammatory protein IL-1β from the kidney and systemic elevation of it in the circulation matched the induction of FGF-23. Serum PTH was also not changed within the first month. We report here that elevations in circulating intact-FGF-23 coincide with the earliest indicators of renal dysfunction (P14), and precede changes in serum phosphate or iron homeostasis. We profiled the sequential presentation of indicators of renal dysfunction, phosphate imbalance, and iron bioavailability and transport to identify the events that initiate osteocytic production of FGF-23 during the onset of CKD.
To determine the identity of the signal from the kidney inducing upregulation of osteocytic FGF-23 at the onset of CKD we utilized a mouse model of congenital CKD that fails to properly mature the glomerular capillary tuft.
Alternately, recent evidence also supports a regulatory role of inflammatory cytokines in the modulation of FGF-23 expression. Iron status is inversely correlated to the level of circulating FGF-23, and improvement in iron bioavailability within patients correlates with a decrease in FGF-23. FGF-23 has arisen as an early biomarker of renal dysfunction, but at the onset of chronic kidney disease (CKD) data suggest that FGF-23 may be produced independently of the parathyroid hormone (PTH), 1,25(OH) 2-Vitamin D 3 signaling axis.