P0899BIOMARKERS OF CKD-MBD IN CHILDREN
Authors: Balmukhanova Altynay , Kanatbayeva Assiya , Kabulbayev Kairat , Shepetov Abay , Balmukhanova Aigul 
Published: June 2020

Abstract

Background and Aims
In recent years there has been a growth in the number of patients with chronic kidney disease (CKD). As it is known, one of the most severe complications of CKD is mineral and bone disorder (MBD). MBD, which develops in childhood, contributes not only to the development of degenerative bone disease, but also to the growth of vascular morbidity and mortality in adulthood. Therefore, adequate control of bone and mineral metabolism is one of the goals in the treatment of children with CKD. Due to the recently discovered FGF-23, a significant role in the pathogenesis of MBD is given to hyperphosphatemia as the initiator of the process. However, changes in value of phosphorus and parathyroid hormone (PTH) are revealed only on the last stages of the disease. FGF-23 is a protein, which produced in bone cells and nowadays it is considered to be the central regulator of mineral-bone metabolism. It increases the loss of phosphorus in the urine due to the blockade of the sodium-phosphorus transporter in the proximal tubule of the nephron. FGF-23 also inhibits 1α-hydroxylase and stimulates 24-hydroxylase, leading to accelerated degradation of the active form of vitamin D.
Thus, the aim of our study was to investigate the relation between FGF-23 and other markers of bone metabolism such as phosphorus and parathyroid hormone.

Method
The study was conducted on 73 children (38 boys and 35 girls) with different stages of CKD. An average age of the patients was 9.89 ± 0.57 years. Exclusion criteria: active inflammatory, bone, infectious, oncological, immunological diseases; taking steroids and vitamin D supplements. We performed further laboratory tests: phosphorus, PTH, vitamin D and FGF-23. Serum concentration of intact FGF-23 was assessed by using the kit for ELISA method (Biomedica Medizinprodukte GmbH, Austria). This study was approved by the local scientific ethics committee of National medical university. Ethical standards and rights of patients were not violated. Descriptive statistics and correlation analysis were performed in MS Excel 2016 and SPSS 18.0.

Results
The laboratory tests results revealed that the mean value of phosphorus was 1.77±0.04 mmol/l among all patients with different stages of CKD. There were 29 (33.3%) children with hyperphosphatemia. The most of these patients were ESRD and they needed a renal replacement therapy. No patients with CKD 1-3 stages had high level of phosphorus. The values of PTH increase as CKD progresses. The patients with the first and second stages had absolutely normal PTH value and only 2 patients with the third stage had slightly elevated level. Only 1 out of 17 patients on dialysis (both hemodialysis and peritoneal dialysis) had an acceptable PTH value. By contrast, there was a vitamin D deficiency (a mean value was 22.4±1.64 ng/ml).
The results of identification FGF-23 by the ELISA kit showed that there was also a gradual increase in its level depending on the stage of the disease. Moreover, there were 14 (19.2%) children with elevated FGF-23 concentration though other markers of bone metabolism were normal.
The correlation analysis revealed positively significant associations between FGF-23 and phosphorus (r=0.60, p=0.00), FGF-23 and PTH (r=0.68, p=0.00).

Conclusion
Overall, our investigation proved that FGF-23 is positively correlated to phosphorus and PTH. Furthermore, in most cases, FGF-23 responds much sooner than other markers of mineral and bone metabolism and its increased value might be an early predictor of mineral and bone disorder. However, more research is required in this area.