Persistence of Vascular Calcification after Reversal of Uremia

Abstract

The extent to which vascular calcification is reversible and the possible mechanisms are unclear. To address this, calcified aortas from uremic mice were transplanted orthotopically into normal mice, and the calcium content, histology, and minerals of the allografts were compared with the nontransplanted donor aorta. Calcium content decreased immediately after transplantation but remained constant thereafter, with 68% AE 12% remaining after 34 weeks. X-ray diffraction showed the presence of apatite in both donor aortas and allografts. Osteoclasts were absent in the allografts and there was no expression of the macrophage marker CD11b, the osteoclast marker tartrate-resistant acid phosphatase, or carbonic anhydrase II. The initial loss of calcium was less in heavily calcified aortas and was associated with an increase in the Ca/P ratio from 1.49 to 1.63, consistent with a loss of nonapatitic calcium. The results indicate that vascular calcification persists after reversal of uremia, because of a lack of active resorption of apatite. This failure to resorb established calcifications may contribute to the severity of vascular calcification and suggests that therapy should be aimed at prevention.

Vitamin D in Vascular Calcification: A Double-Edged Sword?

“…Following the recognition of additional extraosseous bone-like mineralised tissue within these vessels, VC was subsequently acknowledged as an active, pathobiological process with some features of bone morphogenesis, but also displaying distinct cellular and molecular processes. A recent study emphasised this concept by demonstrating the propensity of VC to persist despite correcting for mineral imbalance within an adenine-induced advanced CKD animal model [ 27 ]. In this study, aortic calcification was exacerbated in CKD-induced mice by supplementation of a high-phosphate diet and periodic administration of calcitriol (1,25-dihydroxyvitamin D3).…”

“…In this study, aortic calcification was exacerbated in CKD-induced mice by supplementation of a high-phosphate diet and periodic administration of calcitriol (1,25-dihydroxyvitamin D3). Lomashvili et al were then able to elegantly demonstrate that upon dissecting and transplanting segments of calcified aorta into healthy littermates, moderate decreases in aortic calcium content could be initially observed, but calcified tissue persisted and remained intact after a 35 week follow-up period [ 27 ]. Furthermore, calcified vessels continued to mineralise with calcium-phosphate deposition similar to that of hydroxyapatite in bone.…”

Vascular Calcification Slows But Does Not Regress After Kidney Transplantation

“… 3 , 4 Whether this lesion can be arrested or reversed is unclear, as existing calcifications or permanent changes to matrix proteins produced by uremia could enable progression despite normalization of renal function and mineral metabolism. Our previous studies in which calcified aortas from uremic mice were transplanted into normal mice showed no evidence of regression, 5 but the possibility of regression over longer periods of time remains unanswered and has important clinical implications.…”

Exogenous BMP7 in aortae of rats with chronic uremia ameliorates expression of profibrotic genes, but does not reverse established vascular calcification

“…In the present investigation, elimination of hyperphosphatemia or of the uremic milieu did not result in any regression of established VC. Lomashvili et al have studied the reversibility of calcitriol-induced uremic VC [ 46 ]. In parallel with the present ATx-model they performed an allogenic transplantation of a calcified aorta from uremic animals into healthy animals and examined the effect on VC.…”