Negli ultimi anni è stato dimostrato che molti tessuti non solo esprimono il recettore per la Vitamina D (VDR), ma possiedono anche l’enzima 1,alfa-idrossilasi, che converte la 25 (OH)D circolante a 1,25 (OH) D3; ad oggi, i meccanismi che regolano la conversione extrarenale che avviene nella cute, nel colon, nella prostata, nei macrofagi e altri organi non è completamente conosciuto.
Glenville Jones Seminars in Dialysis—Vol 20, No 4 (July–August) 2007
pp. 316–324
Physiological serum levels of calcitriol can suppress nonrenal calcitriol synthesis, in advanced kidney disease, the high concentrations of calcitriol or its analogs required to suppress PTH could adversely impact calcitriol autocrine/ paracrine actions through feedback inhibition of 1-hydroxylase expression and activity and also through the induction of 24-hydroxylase to degrade the already low serum 25(OH)D.
CKD not only induces vitamin D deficiency but also impairs 25(OH)D uptake by nonrenal cells expressing 1-hydroxylase,so normal serum 25(OH)D levels may be insufficient to sustain ‘autocrine/ paracrine’ calcitriol actions in CKD. A defective uptake of 25(OH)D also appears to occur in parathyroid cells, which express 1-hydroxylase.
This meta-analysis includes observational
and interventional studies investigating multiple cardiometabolic
end points in response to vitamin D supplementation and UVB
radiation. The trials showed no clinically significant effect of
vitamin D supplementation at the doses studied, and the authors
suggest that further well-designed randomized, prospective trials
Trial data available to date are unable to demonstrate a statistically significant reduction
in mortality and cardiovascular risk associated with vitamin D.
This is a recent
meta-analysis of a large number of intervention trials; it found
no significant reduction in overall cardiovascular risk or mortality,
or blood pressure, associated with vitamin D supplementation.
The authors note significant heterogeneity of study design
and analysis and rate the quality of available evidence as low to
moderate.
Correction of renal megalin levels by early interventions with paricalcitol could partially account for the efficacy of the analog in ameliorating albuminuria at early stages of kidney disease and for the low phosphatemic activity of the analog.
renoprotective properties of Vit D:Autocrine/paracrine VDR activation in mesangial cells, podocytes, tubular cells, fibroblasts, resident or infiltrating macrophages, and immune cells.
The identification of accurate serum markers of PTH-independent renoprotection should help monitor the safety and efficacy of vitamin D interventions: TACE, direct anti-TACE properties of vitamin D. Clinical studies are necessary to evaluate the accuracy of simple measurements of monocyte TACE content
Randomized trial evidence was sparse, and few trials assessed these outcomes as primary prespecified endpoints.
cholecalciferol and ergocalciferol are not equivalent
The shorter duration of the correction of vitamin D deficiency by ergocalciferol due to the shorter half-life of 25(OH)D2 compared with that of 25(OH)D3 can be easily resolved with daily oral doses of 2000 IU of either metabolite, which results in identical increases in serum 25(OH)D from baseline.
almost 50% of the administered vitamin D is rapidly converted to 25(OH)D at doses o2000 IU. In contrast, much lower conversion rates occur with daily vitamin D dosage > 2000–4000 IU,because Vit d is stored in fat.
Direct supplementation with 25(OH)D is available in Europe, half-life is 15 to 18 days. Clearly, daily or weekly regimens could result in increases in serum 25(OH)D concentrations to toxic levels.
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