FGF-23 and sFRP-4 in Chronic Kidney Disease and Post-Renal Transplantation

Abstract

Background: The phosphatonins fibroblast growth factor-23 (FGF-23) and FRP-4 are inhibitors of tubular phosphate reabsorption that may play a role in the hyperphosphatemia associated with chronic kidney disease (CKD) or in the hypophosphatemia associated with renal transplants. Methods: Plasma FGF-23, FRP-4, phosphorus and parathyroid hormone were measured in patients at all stages of CKD. Phosphate regulation of FGF-23 and secreted frizzled related protein-4 (sFRP-4) was examined in end-stage renal disease patients in the presence and absence of therapeutic phosphate binder usage. In renal transplant patients, plasma FGF-23, sFRP-4 and phosphorus concentrations were determined before and 4–5 days after transplantation. Results: Plasma FGF-23 correlated with creatinine clearance (r² = –0.584, p < 0.0001) and plasma phosphorus (r² = 0.347, p < 0.001) in CKD patients and with plasma phosphorus (r² = 0.448, p < 0.001) in end-stage renal disease patients. Phosphate binder withdrawal increased FGF-23 levels. In kidney transplant patients, dramatic decreases in FGF-23 (–88.8 ± 5.4%) and phosphorus (–64 ± 10.2%) were observed by 4–5 days post-transplantation. In patients with post-transplant hypophosphatemia, FGF-23 levels correlated inversely with plasma phosphorus (r² = 0.661, p < 0.05). sFRP-4 levels did not change with creatinine clearance or hyperphosphatemia in CKD or end-stage renal disease patients, and no relation was noted between post-transplant sFRP-4 levels and hypophosphatemia. Conclusions: In CKD, FGF-23 levels rose with decreasing creatinine clearance rates and increasing plasma phosphorus levels, and rapidly decreased post-transplantation suggesting FGF-23 is cleared by the kidney. Residual FGF-23 may contribute to the hypophosphatemia in post-transplant patients.

Complications and Managements of Hyperphosphatemia in Dialysis

“…The association between use of phosphorus binders and survival was observed within each quartile of baseline serum phosphorus except the lowest. Results from human data suggest that lowering of phosphorus levels by intake of phosphate binders will substantially reduce serum FGF-23 levels (Koiwa et al, 2005;Pande et al, 2006). In this prospective observational study, treatment with phosphate binders was associated with a reduced 1-year mortality among incident hemodialysis patients ).…”

Phosphorus and Calcium Metabolism Disorders Associated with Chronic Kidney Disease Stage III-IV (Systematic Review and Meta-Analysis)

“…The morphogenetic proteins (FGF-23 and Klotho) regulate homeostasis of phosphates, vitamin D and bone tissue mineralization. The level FGF-23 (fibroblasts growth factor 23, produced mostly by osteocytes) is increased even at the pre-dialysis stage of CKD [Gutiérrez, 2009;Jean, 2009;Pande , 2006;Razzaque 2008Razzaque , 2009Zemchencov, 2009]. The role of circulating FGF-23 level increase at various CKD stages is being studied.…”

“…Later, when the CKD IV-V results in GFR decrease, the elevated FGF-23 level is not enough to prevent hyperphosphatemia and hyperparathyroidism. Prospective studies [Gutiérrez, 2009;Jean, 2009;Pande, 2006;Razzaque, 2009] demonstrate that elevated FGF-23 level in CKD patients at the stage of dialysis initiation is associated with mortality and vascular calcification independent of other risk factors or serum phosphorus and iPTH levels. Therefore, FGF-23 is the potential independent uremic toxin ( Table 2).…”

FGF-23: estado da arte

“…56 Another study involving six dialysis patients has shown that the suspension of P binders increased FGF-23 levels, although not significantly. 57 Our group has studied prospectively the effects of P binders, calcium acetate and sevelamer hydrochloride, in hemodialysis patients and has observed a significant reduction in FGF-23 levels after one year of treatment, and patients treated with sevelamer hydrochloride had a more significant reduction than those treated with calcium acetate. 52 …”