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.

• Authors: Sangeeta Pande, Cynthia S Ritter, Marcos Rothstein, Karen Wiesen, John Vassiliadis, Rajiv Kumar, Susan C Schiavi, Eduardo Slatapolsky, Alex J Brown
• Journal: Nephron. Physiology (Nephron Physiol) Vol. 104 Issue 1 Pg. p23-32 ( 2006) ISSN: 1660-2137 [Electronic] Switzerland
• PMID: 16691036 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• FGF23 protein, human
• Parathyroid Hormone
• Phosphates
• Proto-Oncogene Proteins
• SFRP4 protein, human
• Fibroblast Growth Factors
• Fibroblast Growth Factor-23

Topics

• Female
• Fibroblast Growth Factor-23
• Fibroblast Growth Factors (blood)
• Humans
• Hypophosphatemia (blood, metabolism)
• Kidney Failure, Chronic (blood, metabolism)
• Kidney Transplantation
• Kidney Tubules (metabolism)
• Male
• Parathyroid Hormone (blood)
• Phosphates (blood, metabolism)
• Postoperative Complications (blood)
• Proto-Oncogene Proteins (blood)