Renal aKlotho expression, fibroblast growth factor 23 and parathyroid hormone in experimental modeling of early stages of chronic kidney injury

THEAIM. To determine changes of aKlotho protein kidney expression, circulating levels of fibroblast growth factor 23 (FGF23) and intact parathyroid hormone (PTH) and the parameters of inorganic phosphate (Pi) exchange in experimental modeling of early stages of chronic kidney disease. MATERIAL AND METHODS. The experimental models the chronic kidney injury were 3/4 or 5/6 nephrectomy (NE) in SHR rats while sham-operated SHR rats served as control groups. The duration of experiments was 1 or 2 months. The indices of Pi urinary excretion were determined as well as renal aKlotho protein expression by immunohistochemistry, serum concentrations of FGF23 and PTH (by enzyme-linked immunosorbent assay). RESULTS. The implemented models corresponded to 1C-3C stages of chronic kidney disease. Renal excretion of Pi was significantly increased in the groups of nephrectomized animals. No significant differences were observed in the serum concentration of FGF23 and PTH between control and experimental groups. FGF23 levels were significantly higher only in model of 5/6NE in compare to control groups. In contrary, the renal expression of aKlotho protein was significantly lower in all experimental models of 3/4NE, 5/6 NE compared to the control (sham-operated SHR, 1 month). Moreover, a significant reduction of aKlotho protein was identified at the earliest stage of kidney damage among models applied that was sham-operated SHR, 2 months (vs. sham-operated SHR, 1 month). CONCLUSION. Changes in FGF23/aKlotho system preceeds development of secondary hyperparathyroidism; in early stages of chronic kidney injury the reduction aKlotho in kidney occurs earlier than the systemic increase of FGF23; increase of relative and absolute phosphate excretion in the early stages of experimental CKD is independent from aKlotho, FGF23 and PTH.

aKlotho, Klotho, fibroblast growth factor 23, parathyroid hormone, experimental modeling, chronic kidney injury, chronic kidney disease, inorganic phosphate, urinary excretion

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