FGF23, alpha-Klotho and vitamin D mediated calcium-phosphate metabolism in haemodialysis patients

J Med Biochem. 2021 Mar 12;40(2):160-166. doi: 10.5937/jomb0-27408.

Abstract

Background: Klotho is a prote˝in that acts as a co-receptor for FGF23. FGF23-Klotho axis has great importance regarding the regulation of mineral metabolism by kidneys. In this study, we analysed FGF23, Klotho, 1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D, parathormone, Calcium and Phosphate levels of haemodialysis patients in order to investigate the nature of the mineral metabolism disruption in chronic kidney diseases.

Methods: Sixty haemodialysis patients and 34 healthy controls were included in the study. Serum iFGF, cFGF, and soluble Klotho were analysed using ELISA kits. Moreover, 1,25-dihydroxyvitamin D3 was determined using LCMS/MS. Calcium, phosphate, iPTH and 25-hydroxyvitamin D were measured using autoanalyzers.

Results: In haemodialysis patients, iFGF23, cFGF23, iPTH and P levels were significantly higher, and 1,25-dihydroxyvitamin D3, Klotho and Ca levels were significantly lower compared with the control group. There was no significant difference in the 25-hydroxyvitamin D levels.

Conclusions: Our study showed that lack of sufficient amounts of Klotho is crucial for mineral metabolism disruptions seen as a complication of chronic kidney diseases. Despite the high levels of the hormone, FGF23 is unable to accomplish its function properly, likely due to deteriorated kidney function in haemodialysis patients.

Uvod: Klotho je protein koji deluje kao koreceptor za FGF23. Osa FGF23-Klotho ima veliku važnost u regulaciji metabolizma minerala u bubrezima. U ovom istraživanju analizirali smo nivoe FGF23, Klotho, 1,25-dihidroksivitamina D3, 25-hidroksivitamina D, parathormona, kalcijuma i fosfata kod pacijenata na hemodijalizi kako bismo istražili prirodu poremećaja metabolizma minerala u hroničnim bubrežnim bolestima.

Metode: U istraživanje je uključeno šezdeset pacijenata na hemodijalizi i 34 zdrave osobe u kontrolnoj grupi. Serumi iFGF, cFGF, i rastvorljivi Klotho su analizirani korišćenjem ELISA kompleta. Korišćenjem LC-MS/MS određen je 1,25-dihidroksivitamin D3. Kalcijum, fosfat, iPTH i 25-hidroksivitamin D mereni su korišćenjem autoanalizatora.

Rezultati: Kod bolesnika na hemodijalizi nivoi iFGF23, cFGF23, iPTH i P su bili značajno viši, a nivoi 1,25-dihidroksivitamina D3, Klotho i Ca bili su značajno niži u poređenju sa kontrolnom grupom. Nije bilo značajne razlike u nivoima 25-hidroksivitamina D.

Zaključak: Istraživanje je pokazalo da je nedostatak dovoljnih količina Klotho presudan za poremećaje metabolizma minerala koji se smatraju komplikacijom hroničnih bolesti bubrega. Uprkos visokom nivou, hormon FGF23 nije u mogućnosti da pravilno obavlja svoju funkciju, verovatno zbog pogoršane funkcije bubrega kod pacijenata na hemodijalizi.

Keywords: FGF23; Klotho; calcium-phosphate metabolism; haemodialysis; vitamin D.