Fibroblast growth factor-23 and fetuin-A in black South African children with chronic kidney disease

Abstract

Background. Both fibroblast growth factor-23 (FGF-23) and fetuin-A levels have been implicated in mineral and bone disorders associated with chronic kidney disease (CKD), and several single nucleotide polymorphisms (SNPs) of the fetuin-A gene have also been associated with fetuin-A levels.

Objectives. This study aimed to determine the relationship between FGF-23 and fetuin-A and to determine the role of fetuin-A SNPs with respect to fetuin-A levels and markers of bone mineralisation in black South African children.

Methods. Blood samples from 93 children (5 - 18 years) with various stages of CKD were assessed for C-reactive protein (CRP), calcium, phosphate, parathyroid hormone, 25-hydroxyvitamin D, FGF-23 and fetuin-A levels. Genomic DNA was extracted from whole blood and regions of the fetuin-A gene amplified by polymerase chain reaction. SNPs were genotyped by restriction fragment length polymorphism analysis or by direct sequencing.

Results. The median FGF-23 and fetuin-A levels were 28.9 (11.7 - 147.1) pg/mL and 57.7 (37.7 - 71.8) mg/dL, respectively. A significant negative relationship between fetuin-A and FGF-23 was only observed in the CKD V group (p=–0.60, p<0.001). Plasma FGF-23 levels correlated better with markers of bone mineralisation than fetuin-A. We found significant association of the fetuin-A SNPs rs4918-G and rs2070633-T alleles with log-transformed fetuin-A levels. Serum phosphate and parathyroid hormone levels were also associated with fetuin-A SNPs.

Conclusion. Plasma FGF-23 levels increase with CKD progression while changes in fetuin-A levels are more likely to be observed in children with advanced CKD; and FGF-23 correlated better with markers of bone mineralisation than fetuin-A.