We shall start with VD pathology in patients with renal disease and at the end of our review the topic vitamin D metabolism after kidney transplantation will be discussed. Early changes in renal function are associated with significant changes in VD metabolism. In summary, the kidney is closely linked to the VD axis and calcium-phosphorus homeostasis. Furthermore, soluble klotho causes hypophosphatemia and phosphaturia independently of FGF-23 and is regarded as an early marker of CKD.
It also potentiates 1,25VD-associated renal calcium absorption.
Soluble klotho downregulates insulin-like growth factor I, thus exerting antiaging properties. A soluble klotho was also detected, functioning as humoral factor. Alfa-klotho is a protein cofactor for FGF-23 signaling, as it forms complexes with FGF-23 receptor, thus increasing its affinity for the hormone.
In addition, extrarenal effects have been described on cardiovascular system and brain. In healthy subjects, FGF-23 suppresses PTH secretion. The basic interactions of the kidney in the mineral bone metabolism are shown in Figure 2. In addition, the proximal tubules are the target of major phosphatonins, such as FGF-23 (by α-klotho-dependent mechanism) and PTH. Furthermore, 1,25VD is involved in osteoclast activation and differentiation, as well as osteoblast activation thus taking part in bone remodeling. Apart from activation of VD, the kidneys increase calcium and phosphorus reabsorption in the tubules under the influence of 1,25-dihydroxyvitamin D (1,25VD). The kidney is crucial in maintaining calcium-phosphorus metabolism.
Of utmost importance for the nephrologist are the renoprotective properties of vitamin D, which are based on renin-angiotensin-aldosterone system suppression, nucleotide factor-kB downregulation, Wnt/β-catenin pathway suppression, and upregulation of slit diaphragm protein synthesis. Together with the widely distributed vitamin D receptor (VDR) in human body, these data are the basis of the suggested pleiotropic effects of VD. However, nonrenal CYP27B1, transforming 25VD into 1,25VD, was detected in other tissues-skin (basal keratinocytes, hair follicles), lymph nodes (granulomata), colon (epithelial cells and parasympathetic ganglia), pancreas (islets), adrenal medulla, brain (cerebellum and cerebral cortex), and placenta (decidual and trophoblastic cells). The proximal tubules are the major site for activation of vitamin D (VD). Parathyroid hormone (PTH), prolactin, human growth hormone, low serum calcium, and phosphorus increase CYP27B1 activity, whereas 1,25dihydroxyvitamin D, thyroid hormones, metabolic acidosis, and fibroblast growth factor-23 (FGF-23) suppress its activity. CYP27B1 activity is influenced by different factors.
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