FGF-23, microRNA and phosphate binders intake: Is there a relationship?

Introduction. Hyperphosphatemia significantly increases the risk of developing cardiovascular pathology, as well as the risk of mortality. In regulating phosphate levels, maintaining a phosphate-restricted diet, adequate dialysis in patients on renal replacement therapy, and the use of phosphate-binding drugs play an important role. The pleiotropic effects of phosphate binders, in particular sevelamer, are known: in addition to reducing serum phosphate levels, they also improve endothelial function, reduce the progression of vascular calcification, and reduce the level of FGF-23, the high level of which is associated with left ventricular myocardial hypertrophy (LVH). Currently, extensive research is being conducted to study the post-transcriptional regulation of the genome, in particular microRNAs. microRNAs are small non-coding RNAs involved in regulating the functioning of both healthy and damaged cells. Changes in their expression have been described in many diseases.

Aim. To determine statistically significant associations between microRNA-21, microRNA-126, and microRNA-210 and calciumphosphorus metabolism parameters, FGF-23, and heart remodeling parameters, and to evaluate the effect of phosphate-binding therapy on these parameters.

Materials and methods. The study included 75 patients with CKD G5(D) on renal replacement therapy (hemodialysis – 53 patients and peritoneal dialysis – 22 patients). The control group consisted of 28 healthy volunteers. All patients underwent determination of total calcium, inorganic phosphorus, alkaline phosphatase, parathyroid hormone, FGF-23 in the blood serum by enzyme-linked immunosorbent assay (ELISA), and the level of expression of microRNA-21, microRNA-126 and microRNA-210 in blood plasma by real-time polymerase chain reaction. Instrumental studies included echocardiography. A separate group of patients was identified who received treatment with phosphate binders for > 1 month: totally 43 patients, and 22 of them received sevelamer carbonate at an average dosage of 4800 mg/day.

Results. Differences were noted in the level of FGF-23 in the blood serum of patients on hemodialysis and peritoneal dialysis: in the group of patients on hemodialysis, the concentration of FGF-23 was higher [30.4 [15.3; 69.81]; 15.3 [1.86; 56.8]; p = 0.022]. The level of FGF-23 in the blood serum significantly correlated with dialysis vintage, the values of creatinine, urea, sodium, glucose, total protein, inorganic phosphorus, PTH and alkaline phosphatase activity (p < 0.05). A direct correlations was found between serum miR-126 and miR-210 and the level of FGF-23 (rs = -0,42; p = 0,04 и rs = 0,31; p = 0,05, respectively). In patients with LVH the level of FGF-23 was significantly higher. In patients receiving sevelamer carbonate the incidence of LVH, as well as levels of FGF-23 (12.4 ± 5.9) was lower, in contrast to the group receiving other phosphate binders (23 ± 7.3; p = 0.003) and PTH (110 ± 27 ng/ml), in the group not receiving the drug – 340 ± 15; p = 0.01. The 12-month treatment with phosphate-binders significantly increase the expression of proangiogenic microRNA-126 (p = 0.002).

Conclusions. The use of phosphate binders, in particular sevelamer carbonate, associated with lower levels of blood phosphorus, FGF-23, PTH and higher levels of expression of proangiogenic microRNA-126.

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