Vitamin D Effects on Bone Homeostasis and Cardiovascular System in Patients with Chronic Kidney Disease and Renal Transplant Recipients

Abstract

Poor vitamin D status is common in patients with impaired renal function and represents one main component of the complex scenario of chronic kidney disease-mineral and bone disorder (CKD-MBD). Therapeutic and dietary efforts to limit the consequences of uremia-associated vitamin D deficiency are a current hot topic for researchers and clinicians in the nephrology area. Evidence indicates that the low levels of vitamin D in patients with CKD stage above 4 (GFR < 15 mL/min) have a multifactorial origin, mainly related to uremic malnutrition, namely impaired gastrointestinal absorption, dietary restrictions (low-protein and low-phosphate diets), and proteinuria. This condition is further worsened by the compromised response of CKD patients to high-dose cholecalciferol supplementation due to the defective activation of renal hydroxylation of vitamin D. Currently, the literature lacks large and interventional studies on the so-called non-calcemic activities of vitamin D and, above all, the modulation of renal and cardiovascular functions and immune response. Here, we review the current state of the art of the benefits of supplementation with native vitamin D in various clinical settings of nephrological interest: CKD, dialysis, and renal transplant, with a special focus on the effects on bone homeostasis and cardiovascular outcomes.

Keywords: CKD–MBD; cardiovascular risk; chronic kidney disease; dialysis; kidney transplant; vitamin D.

Figure 1

The complex interplay between active vitamin D (both circulating and activated by osteoblasts), osteocyte-produced FGF23 and sclerostin, parathyroid gland signaling, and effects on bone cells. Abbreviations: FGF23, fibroblast growth factor 23; BMP-2, bone morphogenic protein-2; Nurr-1, nuclear receptor-related protein-1; DKKI, dickkopf-related protein 1.

Figure 2

Interactions between active vitamin D and FGF23/FGFR4 signaling regarding LVH development at cardiomyocyte level. Active vitamin D counterbalances FGF23-induced LVH both by modifying gene expression and through a direct inhibitory effect on FGF23/FGFR4 transduction pathway. Abbreviations: FGF23, fibroblast growth factor 23; VDRAs, vitamin D receptor agonists; FGFR4, fibroblast growth factor receptor 4; PLCy, phospholipase Cy; NFAT, nuclear factor of activated T cells; LVH, left ventricular hypertrophy.