Active vitamin D is cardioprotective in experimental uraemia but not in children with CKD Stages 3-5.

Background: Uraemic cardiac remodelling is associated with vitamin D and Klotho deficiency, elevated fibroblast growth factor 23 (FGF23) and activation of the renin-angiotensin system (RAS). The cardioprotective properties of active vitamin D analogues in this setting are unclear.

Methods: In rats with 5/6 nephrectomy (5/6Nx) treated with calcitriol, the cardiac phenotype and local RAS activation were investigated compared with controls.

FGF23-Mediated Activation of Local RAAS Promotes Cardiac Hypertrophy and Fibrosis.

Patients with chronic kidney disease (CKD) are prone to developing cardiac hypertrophy and fibrosis, which is associated with increased fibroblast growth factor 23 (FGF23) serum levels. Elevated circulating FGF23 was shown to induce left ventricular hypertrophy (LVH) via the calcineurin/NFAT pathway and contributed to cardiac fibrosis by stimulation of profibrotic factors. We hypothesized that FGF23 may also stimulate the local renin-angiotensin-aldosterone system (RAAS) in the heart, thereby further promoting the progression of FGF23-mediated cardiac pathologies.