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oai:repisalud.isciii.es:20.500.12105/230202024-11-28T21:21:13Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Perez, M. Mar author Ferrer, Miguel D author Lazo-Rodriguez, Marta author Zeralda Canals, Ana author Banon-Maneus, Elisenda author Campistol, Josep M author Miller, Stephan author Garg, Rekha author Gold, Alex author Salcedo, Carolina author Perello, Joan author 2020-10-16 Cardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N=38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Inhibition of CVC was 50-65% with SNF472 3 mg/kg and similar to 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r=0.628, P=0.005). In patients with calciphylaxis (N=14), infusion of SNF472 (similar to 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N=274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r=0.401, P=0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors. Perez MM, Ferrer MD, Lazo-Rodriguez M, Canals AZ, Banon-Maneus E, Campistol JM, et al. A novel assay to measure calcification propensity: from laboratory to humans. Sci Rep. 2020 Oct 16;10(1):17578. 10.1038/s41598-020-74592-x 2045-2322 Scientific Reports https://hdl.handle.net/20.500.13003/19412 33067536 L633190817 2-s2.0-85092594481 https://hdl.handle.net/20.500.12105/23020 585845700022 A novel assay to measure calcification propensity: from laboratory to humans