[Significance of the morphogenetic proteins FGF-23 and Klotho as predictors of prognosis of chronic kidney disease].

AIM: To study the role of the morphogenetic proteins FGF-23 and Klotho in the progression of chronic kidney disease (CKD) and in the development of cardiovascular events, inflammation, protein-energy deficiency, and other complications.

SUBJECTS AND METHODS: Examinations were made in 70 patients with Stages I-VD CKD: 41 with chronic glomerulonephritis (including 10 with nephritis in the presence of diffuse connective tissue diseases), 22 with tubulointerstitial nephritis, and 7 with hypertensive nephrosclerosis. There were a total of 30 men and 40 women whose age was 20 to 84 years; the mean age at the study inclusion was 41 +/- 6.7 years. The serum levels of FGF-23 (Human FGF-23 ELISA kit using monoclonal antibodies to complete molecule of FGF-23) and Klotho (Human alpha-K1 ELISA using anti-Klotho antibodies) were investigated in all the 70 patients with CKD.

RESULTS: The sera of all the examinees with CKD showed elevated FGF-23 and decreased Klotho levels, the magnitude of a change in which increased from Stage I to VD. In patients with different stages of CKD, the increase in FGF-23 levels, as glomerular filtration rate reduced, outstripped that in the serum levels of phosphorus and intact parathyroid hormone. There was a strong correlation of the serum level of the morphogenetic proteins, Klotho in particular, with proteinuria, C-reactive protein level, protein-energy deficiency, indicating the pleiotropic effects of these proteins. There was also a strong correlation between serum Klotho and ferritin levels and transferrin saturation percentage, which suggests that Klotho may be involved in iron regulation.

CONCLUSION: The results of the investigation lend credence to the experimental and clinical findings that the serum levels of the morphogenetic proteins FGF-23 (an increase) and Klotho (a decrease) are early markers for progressive CKD and that their changes begin just in Stage III CKD and progress as renal failure worsens.