Table 1.
The importance of the FGF-23–klotho–sclerostin axis in left ventricular hypertrophy in CKD.
| FGF-23–Klotho–Sclerostin Axis | Cellular Level | Tissue Level | Circulation | Clinical Observation | Therapeutic Potential |
|---|---|---|---|---|---|
| FGF-23 | FGF23 directly induces LVH by binding to the FGFR-4 in cardiomyocytes RAAS activation induces FGF23 expression in cardiac myocytes and stimulates pro-fibrotic crosstalk between cardiac myocytes and fibroblasts |
FGF23 increases production of TGF-β, lipocalin-2, and TNF-α, and thus promoting the inflammation process | LVH is shown to be associated with an increase in both myocardial and serum intact FGF23 FGF23 contributes to renal anemia development -> contribution to LVH aggravation |
FGF23 levels correlate positively with LVH and negatively to left ventricular ejection fraction in patients on hemodialysis | Vitamin D treatment reduces LVH Ferric citrate lowers FGF23 levels and improves cardiac function and patient survival |
| Klotho | Cardioprotective effect by downregulation of TRPC6 channels in cardiomyocytes, important for angiotensin II-induced hypertrophy signaling Klotho upregulation inhibits TGF-β1-induced fibrosis and pathogenic Wnt/ β-catenin signaling in cardiomyocytes |
Cardiomyocytes and cardiac fibroblasts express klotho | Uremic serum or TGF-β1 suppressed klotho expression by cardiomyocytes | FGF23/klotho ratio correlates with changes in left ventricular mass Low klotho levels are associated with CV events Serum klotho is an independent biomarker of a left ventricular mass index |
Klotho administration attenuates high-phosphate induced renal and cardiac fibrosis and improved both renal and cardiac function |
| Sclerostin | Lacking data about the association with LVH | Lacking data | Lacking data | Elevated serum sclerostin levels in patients with aortic valve calcification with increased upregulation of sclerostin mRNA | Not yet clear whether therapeutic decrease of sclerostin levels is beneficial or deleterious for CV outcome |
Abbreviations: LVH—left ventricular hypertrophy; RAAS—renin–angiotensin–aldosterone system; TRPC6—transient receptor potential canonical type 6; TGF-β—transforming growth factor β; TNF-α—tumor necrosis factor α.