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Klotho, fibroblast growth factor 23 and inorganic phosphate in early stages of cronic kidney disease

Abstract

THE AIM: to ascertain whether aKlotho and FGF23 are associated with inorganic phosphate urinary excretion in early stages of chronic kidney disease (CKD). PATIENTS AND METHODS. The cross-sectional study included 80 patients (age 40.3±16.1) with primary immune glomerulopathies and estimated glomerular filtration rate (eGFR) range 30-140 ml/min/1.73 m2. Serum levels of Pi (sPi), intact FGF23, intact PTH, serum αKlotho (sKlotho), urinary αKlotho creatinine ratio (uKlotho/uCr) were analyzed. Renal expression of αKlotho protein (rKlotho) was estimated by morphometric method. Evaluated parameters of renal Pi exchange including fractional excretion of Pi (FEPi) and 24h urinary Pi excretion (uPi24). RESULTS. There are no significant differences of sPi and uPi24 in groups of patients with eGFR 140-100, 99-70, 69-50 и 49-30 ml/min/1.73 m2. The level of FEPi increased gradually along with fall of eGFR of 99-70 ml/min/1.73 m2 (р<0.001). FEPi level significantly increased during decrease of eGFR (р<0,001). Compared to eGFR 140-100 ml/min/1.73 m2 rKlotho expression in tubular epithelium was significantly lower at eGFR 99-70 ml/min/1.73 m2, while sKlotho concentration decreased at eGFR 69-50 ml/min/1.73 m2. sKlotho concentration was significantly associated with eGFR, interstitial fibrosis, and glomerular sclerosis. During eGFR decrease the level of PTH increased significantly at eGFR 99-70 ml/min/1.73 m2 compared to eGFR 140-100 ml/min/1.73 m2. The level of FGF23 was significantly higher in patients with eGFR 49-30 ml/min/1.73 m2. In patients with eGFR > 50 ml/min/1.73 m2 no correlations were found between aKlotho/FGF23 and indices of Pi metabolism. FGF23 was associated with sPi in patients with eGFR < 50 ml/min/1.73 m2. In the same groups FEPi was associated with PTH level. Neither Klotho nor FGF23 were associated with indices of urinary Pi excretion in multivariable regression analysis. sPi was independently associated with FGF23 (ß=0.50; р=0.007), while FEPi with PTH (ß=0.43; р=0.003). CONCLUSION. The decline of αKlotho in serum and kidneys occurs on early stages of CKD and apparently associates with tubulointerstitial injury preceding the increase of FGF23. In early stages of CKD the alterations in tubular reabsorption and renal excretion of Pi as important factor of this anion neutral balance support occur independently of circulating FGF23 and renal αKlotho.

About the Authors

E. O. Bogdanova
Pavlov First Saint Petersburg State Medical University Institute of Nephrology
Russian Federation


O. V. Galkina
Pavlov First Saint Petersburg State Medical University Institute of Nephrology
Russian Federation


I. M. Zubina
Pavlov First Saint Petersburg State Medical University Institute of Nephrology
Russian Federation


V. A. Dobronravov
Pavlov First Saint Petersburg State Medical University Institute of Nephrology
Russian Federation


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Review

For citations:


Bogdanova E.O., Galkina O.V., Zubina I.M., Dobronravov V.A. Klotho, fibroblast growth factor 23 and inorganic phosphate in early stages of cronic kidney disease. Nephrology (Saint-Petersburg). 2016;20(4):54-61. (In Russ.)

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ISSN 1561-6274 (Print)
ISSN 2541-9439 (Online)