Introduction: Calciprotein particles (CPPs) are potentially modifiable mediators of phosphate toxicity in patients with kidney disease. We compared the effects of calcium carbonate (CC) and the non-calciumbased phosphate binder sevelamer on CPP levels in patients undergoing hemodialysis (HD). We hypothesized that treatment with sevelamer would achieve greater reductions in amorphous calcium phosphate-containing CPP (CPP-1) and hydroxyapatite-containing CPP (CPP-2) owing to reduced calcium loading and anti-inflammatory pleiotropic effects. Methods: We conducted an open-label, randomized controlled trial (RCT) in which 31 stable prevalent HD patients were allocated to receive either sevelamer hydrochloride (SH), sevelamer carbonate (SC), or CC for 24 weeks. Dual primary endpoints were the between groups differences in serum CPP-1 and CPP-2 levels at 24 weeks in SH þ SC-treated versus CC-treated patients. Effects on aortic pulse wave velocity (aPWV), inflammatory cytokines (interleukin-6 and-8), and effects across individual treatment arms were also assessed. Results: Serum CPP-1, but not CPP-2, levels were lower in those randomly assigned to the sevelamer (SH þ SC) group compared with the CC group at 24 weeks (-70%, 95% confidence interval [CI]-90% to-15%, P ¼ 0.02). In subgroup analysis, this effect was confined to those receiving SC (-83.4%, 95% CI-95.7% to-36.8%, P ¼ 0.01). aPWV and interleukin-8 levels were also lower in those who received sevelamer compared with CC at 24 weeks (-2.0 m/s, 95% CI-2.9 to-1.1;-57%, 95% CI-73% to-30%, respectively, both P ¼ 0.01). Conventional markers of mineral metabolism remained stable across all treatment groups. Discussion: Compared with treatment with CC, use of sevelamer for 24 weeks was associated with lower serum CPP-1 levels and a reduction in aPWV and systemic inflammation.
Purpose of review Calciprotein particles (CPP) are formed in supersaturated solutions of calcium, phosphate and the mineral-binding protein fetuin-A. CPP have garnered considerable interest as potential mediators of mineral stress, but little consideration has been given to their origin, clearance and role in metabolism. Recent findings CPP are made whilst buffering the mineral absorbed from the intestine after a meal or during remodelling of bone matrix. The postprandial rise in circulating CPP rise may be sensed by osteoblasts/osteocytes in bone, stimulating the secretion of the master phosphatonin fibroblast growth factor 23. Amorphous calcium phosphate-containing CPP are rapidly cleared by endothelial cells in the liver whereas crystalline apatite-containing CPP are filtered by phagocytic cells of the reticuloendothelial system. Impaired excretory function in kidney disease may lead to accumulation of CPP and its precursors with possible pathological sequalae. Inability to stabilize CPP in fetuin-A-deficiency states can result in intraluminal precipitation and inflammatory cascades if other mineralisation regulatory networks are compromised. Summary CPP allow efficient transport and clearance of bulk calcium phosphate as colloids without risk of precipitation. As circulating factors, CPP may couple dietary mineral exposure with endocrine control of mineral metabolism in bone, signalling the need to dispose of excess phosphate from the body.
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