Role of Vitamin D in Uremic Vascular Calcification

Abstract

The risk of cardiovascular death is 10 times higher in patients with CKD (chronic kidney disease) than in those without CKD. Vascular calcification, common in patients with CKD, is a predictor of cardiovascular mortality. Vitamin D deficiency, another complication of CKD, is associated with vascular calcification in patients with CKD. GFR decline, proteinuria, tubulointerstitial injury, and the therapeutic dose of active form vitamin D aggravate vitamin D deficiency and reduce its pleiotropic effect on the cardiovascular system. Vitamin D supplement for CKD patients provides a protective role in vascular calcification on the endothelium by (1) renin-angiotensin-aldosterone system inactivation, (2) alleviating insulin resistance, (3) reduction of cholesterol and inhibition of foam cell and cholesterol efflux in macrophages, and (4) modulating vascular regeneration. For the arterial calcification, vitamin D supplement provides adjunctive role in regressing proteinuria, reverse renal osteodystrophy, and restoring calcification inhibitors. Recently, adventitial progenitor cell has been linked to be involved in the vascular calcification. Vitamin D may provide a role in modulating adventitial progenitor cells. In summary, vitamin D supplement may provide an ancillary role for ameliorating uremic vascular calcification.

Mineral bone disorders in chronic kidney disease

“…Traditionally, active vitamin D compounds were used in SHPT patients for its inhibitory effects on PTH gene transcription and chief cell hyperplasia . As CKD progresses, vitamin D deficiency or insufficiency was prominent because of the presence of proteinuria, tubulointerstitial injury and GFR loss . The binding of 25(OH)D to the proximal tubular epithelium megalin receptor is limited during the proteinuria .…”

“…23 As CKD progresses, vitamin D deficiency or insufficiency was prominent because of the presence of proteinuria, tubulointerstitial injury and GFR loss. 24 The binding of 25(OH)D to the proximal tubular epithelium megalin receptor is limited during the proteinuria. 25 As GFR loss, the production of FGF-23 inhibits the 1-α-hydroxylase activity in the renal proximal tubule.…”

Vitamin D supplementation guidelines for Poland – a 2018 update

“…Wykazano, że kalcytriol uczestniczy w licznych procesach fizjologicznych, między innymi wspomaga proliferację i różnicowanie komórek należących do układu immunologicznego [50], indukuje apoptozę komórek nowotworowych i spowalnia ich namnażanie [51,52], nasila produkcję katelicydyny i beta-defensyny [50,[53][54][55], moduluje aktywność limfocytów [50], stosunek limfocytów Th1 do Th2 [50,56], zmniejsza stężenie prozapalnych cytokin (IL-1, TNFα) przy jednoczesnym zwiększeniu stężenia cytokin przeciwzapalnych (IL-4, IL-5, IL-10) [50,57], zmniejsza wydzielanie reniny i w ten sposób redukuje aktywność układu renina-angiotensyna-aldosteron [58,59], hamuje angiogenezę [60][61][62] i korzystnie wpływa na procesy zwapnienia w naczyniach krwionośnych [63][64][65][66], stymuluje syntezę czynników neurotroficznych [67,68], hamuje procesy zwłóknienia w nerkach [69,70], a niedobór witaminy D zmniejsza sekrecję insuliny [71]. Witamina D wykazuje silne działanie immunomodulacyjne [57,72].…”

Mechanisms and Clinical Implications of Vascular Calcifications in Chronic Kidney Disease

“…Taken together, these data suggest that excess calcitriol can promote vascular calcifications through several interrelated mechanisms, while moderate physiological or pharmacological doses are beneficial (by suppressing the expression of osteoblastic genes in VSMCs). Debate also exists concerning the potential differential effects and benefits of native vitamin D as compared to active vitamin D receptor agonists, with an assumption that early administration of nutritional supplementation in CKD patients may prevent vascular calcification [54]. However, this remains to be proven by future research.…”