The integrity of the vitamin D endocrine system is essential for human health. Nutritional vitamin D deficiency
in otherwise healthy individuals, associates with a higher risk of mortality for all causes, despite normal serum calcitriol.
These deadly causes extend beyond the recognized adverse impact of vitamin D deficiency on calcium and phosphate
homeostasis predisposing to secondary hyperparathyroidism, bone loss and vascular calcification. Vitamin D deficiency
also associates with an early onset of disorders of aging, including hypertension, proteinuria, insulin resistance, immune
abnormalities that enhance the propensity for viral and bacterial infections, autoimmune disorders, cancer, and multiple
organ damage due to excessive systemic inflammation causing atherosclerosis, vascular stiffness, renal lesions, and impaired
DNA-damage responses. The frequency and severity of all of these disorders markedly increase in chronic kidney
disease (CKD) because the kidney is essential to maintain serum levels of calcitriol, the most potent endogenous endocrine
activator of the vitamin D receptor (VDR), and also of 25-hydroxyvitamin D, for local rather than systemic VDR activation.
The goal of this review is to update the current understanding of the pathophysiology behind the classical and
non-classical actions of VDR activation that help prevent the onset and/or attenuate the progression of renal and cardiovascular
damage in CKD. This knowledge is essential to identify non-invasive, sensitive and accurate biomarkers of the
severity of these disorders, a first step to generate evidence-based recommendations for a safe correction of vitamin D
and/or calcitriol deficiency in the course of CKD that effectively improves outcomes.
Keywords: Chronic kidney disease, fibroblast growth factor 23, parathyroid hormone, renin-angiotensin-aldosterone-system,
tumor necrosis alpha converting enzyme, vitamin D, vitamin D deficiency, vitamin D receptor.
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