FGF-23 and sFRP-4 in chronic kidney disease and post-renal transplantation.
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.
Pande
Sangeeta
S
Renal Division, Washington University School of Medicine, St. Louis, Mo. 63110, USA.
Ritter
Cynthia S
CS
Rothstein
Marcos
M
Wiesen
Karen
K
Vassiliadis
John
J
Kumar
Rajiv
R
Schiavi
Susan C
SC
Slatapolsky
Eduardo
E
Brown
Alex J
AJ
D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D017674:Hypophosphatemia / Q000097:blood / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010710:Phosphates / Q000097:blood / Q000378:metabolism; D011183:Postoperative Complications / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000097:blood*; D000094742:Secreted Frizzled-Related Proteins
D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D010281:Parathyroid Hormone; D010710:Phosphates; D011518:Proto-Oncogene Proteins; C000717427:FGF23 protein, human; C118723:SFRP4 protein, human; D000094742:Secreted Frizzled-Related Proteins