title: Serum klotho: relation to fibroblast growth factor-23 and other regulators of phosphate metabolism in children with chronic kidney disease.
abstract: FGF23 and Klotho synergize to regulate phosphate homeostasis by promoting renal phosphate excretion. Chronic kidney disease (CKD) may be viewed as a state of FGF23 resistance caused by Klotho deficiency. This viewpoint explains several observations on phosphate metabolism in CKD that lack mechanistic insights. Our objectives were to correlate serum klotho and FGF-23 with other variables that regulate phosphate metabolism. We studied 40 patients with CKD on conservative treatment (group A), 44 patients with end-stage renal disease (ESRD) on regular hemodialysis (group B), 40 kidney transplant recipients (KTR) (group C) and 40 healthy controls for measuring serum klotho and FGF-23. Blood samples were withdrawn for measuring the levels of serum Calcium (Ca), Phosphorus (P), alkaline phosphatase (ALP), 1,25 (OH)2 D3, intact parathyroid hormone (PTH), FGF-23 and α klotho. The mean levels of FGF-23 and α klotho in control group were 225.78 ± 111.05 pg/ml (range: 102.4, 418.5) and 6.78 ± 1.90 ng/ml (range: 4, 11), respectively. The mean levels of FGF-23 in the 3 studied groups were 1,034.2 ± 84.6, 1,288.7 ± 131.4 and 1,008.7 ± 117.6 pg/ml, respectively. The median levels of s-klotho in the 3 studied groups were 3.15, 2.3 and 2.95, respectively. It was found that FGF-23 was significantly increased and α klotho was significantly decreased in all patients when compared with those in the control group (p < 0.001, <0.001, respectively). We found that there was a significant inverse correlation between serum Ca and α klotho in the studied groups. There was no significant correlation between FGF-23 and α klotho in the studied groups (p > 0.05). We have shown that circulating s-klotho was not related to FGF-23 in CKD, dialysis and KTR patients. In addition, we demonstrated a novel association between serum Ca and s-klotho that needs to be further studied.
authors.affiliation: Department of Pediatrics, Cairo University, Cairo, Egypt.
authors.forename: Happy K
authors.initials: HK
authors.lastname: Sawires
authors.forename: Rasha M
authors.initials: RM
authors.lastname: Essam
authors.forename: Marian F
authors.initials: MF
authors.lastname: Morgan
authors.forename: Rasha A
authors.initials: RA
authors.lastname: Mahmoud
mesh_terms: D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000235:genetics*; D005966:Glucuronidase / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation; D000090265:Klotho Proteins; D008297:Male; D010710:Phosphates / Q000378:metabolism*; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000235:genetics* / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins