Klotho Protein, Fibroblast Growth Factor 23 and Renal Calcium Excretion in Initial Stages of Experimental Chronic Kidney Disease

Abstract

INTRODUCTION.It is suggested that fibroblast growth factor 23 (FGF23) and its co-receptor Klotho are probably associatedwith changes in calcium metabolism in chronic kidney disease (CKD) due to ability to regulate intracellular Ca transport bymodulating the cationic channels TRPV5 and TRPV6.THE AIMis to investigate the association between Klotho, FGF23 and renal excretion of Ca in the initial stages of experimental CKD.MATERIAL AND METHODS.The experimental models of chronic kidney injury were resection of the renal tissue in spontaneously hypertensive rats (SHR). Serum concentrations of intact FGF23 and PTH were determined by ELISA, renal Klotho protein expression by IHC. The indices of Ca excretion were calculated.RESULTS.Serum creatinine concentration, creatinine clearance and the severity of interstitial fibrosis in experimental models corresponded to the initial stages of chronic kidney disease. UCa24 and FECa were higher, Klotho protein expression was lower in groups with more severe renal dysfunction, without significant differences in FGF23 and PTH levels. Multiple regression analysis showed that FECa and UCa24 were not associated with FGF23, Klotho, and PTH.CONCLUSION.Renal excretion of Ca in initial stages of experimental kidney damage is not associated with Klotho and FGF23 levels.

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“…Some of these have been investigated. An increase in FGF23 is typical in CKD in response to the renal phosphate retention [ 37 , 38 , 39 , 40 ]. FGF23 was significantly higher in SHR-SO and SHR-NE groups compared to WKY-SO.…”

“…MR was not associated with myocardial α-Klotho mRNA expression. A decrease in renal and circulating α-Klotho is typical for hypertension and CKD [ 34 , 38 , 39 , 40 ], including the models used here. Thus, a decline in α-Klotho kidney production and circulating α-Klotho may be an additional factor in the progression of MR.…”

“…The mechanisms of MR in CKD are poorly understood and may include hemodynamic and non-hemodynamic factors [ 26 , 27 , 28 , 29 , 30 , 31 ]. The increased production of fibroblast growth factor-23 [ 32 , 33 ], αKlotho [ 34 , 35 ], and calcitriol [ 36 ] deficiencies are major candidate non-hemodynamic factors of cardiomyopathy progression in patients with CKD [ 37 , 38 , 39 , 40 ].…”