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A novel assay to measure calcification propensity: from laboratory to humans.
Perez, M Mar; Ferrer, Miguel D; Lazo-Rodriguez, Marta; Canals, Ana Zeralda; Banon-Maneus, Elisenda; Campistol, Josep M; Miller, Stephan; Garg, Rekha; Gold, Alex; Salcedo, Carolina; Perelló, Joan.
Afiliación
  • Perez MM; Sanifit Therapeutics, Parc Bit - Europa Building, 2nd Floor, 07121, Palma de Mallorca, Spain.
  • Ferrer MD; Sanifit Therapeutics, Parc Bit - Europa Building, 2nd Floor, 07121, Palma de Mallorca, Spain.
  • Lazo-Rodriguez M; Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, Palma, Spain.
  • Canals AZ; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
  • Banon-Maneus E; Spanish Kidney Research Network, ISCIII-RETIC REDinREN RD016/0 009, Madrid, Spain.
  • Campistol JM; Sanifit Therapeutics, Parc Bit - Europa Building, 2nd Floor, 07121, Palma de Mallorca, Spain.
  • Miller S; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
  • Garg R; Spanish Kidney Research Network, ISCIII-RETIC REDinREN RD016/0 009, Madrid, Spain.
  • Gold A; Laboratori Experimental de Nefrologia i Trasplantament (LENIT), Fundació Clínic per a la Recerca Biomèdica, Barcelona, Spain.
  • Salcedo C; Spanish Kidney Research Network, ISCIII-RETIC REDinREN RD016/0 009, Madrid, Spain.
  • Perelló J; Sanifit Therapeutics, San Diego, CA, USA.
Sci Rep ; 10(1): 17578, 2020 10 16.
Article en En | MEDLINE | ID: mdl-33067536
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.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Calcinosis / Técnicas de Laboratorio Clínico Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: España

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Calcinosis / Técnicas de Laboratorio Clínico Tipo de estudio: Clinical_trials / Diagnostic_studies / Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Sci Rep Año: 2020 Tipo del documento: Article País de afiliación: España