It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
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 ~ 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 (~ 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.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Sanifit Therapeutics, Palma de Mallorca, Spain
2 Sanifit Therapeutics, Palma de Mallorca, Spain; University of the Balearic Islands, Department of Fundamental Biology and Health Sciences, Palma, Spain (GRID:grid.9563.9) (ISNI:0000 0001 1940 4767)
3 Fundació Clínic per a la Recerca Biomèdica, Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Barcelona, Spain (GRID:grid.428756.a) (ISNI:0000 0004 0412 0974); Spanish Kidney Research Network, ISCIII-RETIC REDinREN RD016/0 009, Madrid, Spain (GRID:grid.413448.e) (ISNI:0000 0000 9314 1427)
4 Sanifit Therapeutics, Palma de Mallorca, Spain (GRID:grid.413448.e)
5 Sanifit Therapeutics, San Diego, USA (GRID:grid.413448.e)
6 Sanifit Therapeutics, San Diego, USA (GRID:grid.413448.e); PharmaDRS Consulting, LLC, San Diego, USA (GRID:grid.413448.e)
7 Sanifit Therapeutics, San Diego, USA (GRID:grid.413448.e); Stanford University, Department of Medicine, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
8 Sanifit Therapeutics, Palma de Mallorca, Spain (GRID:grid.168010.e)
9 Sanifit Therapeutics, Palma de Mallorca, Spain (GRID:grid.168010.e); University of the Balearic Islands, Laboratory of Renal Lithiasis Research, Palma, Spain (GRID:grid.9563.9) (ISNI:0000 0001 1940 4767)