BACKGROUND:Diabetes mellitus (DM) is associated with hyperreactive platelets and increased platelet-leukocyte aggregation (PLA), but the impact of concomitant chronic kidney disease (CKD) has been much less studied. Lipid-lowering treatment (LLT) may have favorable effects on platelet activation and inflammation. The objective of this mechanistic study was to investigate the impact of CKD on platelet function and inflammatory parameters in patients with DM and the effects of LLT. METHODS: After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S + E) were compared in a randomized, double-blind, cross-over study on platelet reactivity, PLA formation and inflammatory parameters. Eighteen DM patients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1.73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DMpatients with eGFR >75 mL/min (DM-only) were included. RESULTS:PLAs were elevated at baseline in DM-CKD compared with DM-only (P = 0.04). S + E reduced PLAs among total leukocytes and neutrophils in DM-CKD patients (P = 0.01 for both) but not in the DM-only group. Platelet reactivity did not differ between patient groups or with LLT. Plasma levels of sCD40L (P < 0.001), elastase (P < 0.01) and von Willebrand factor (VWF) (P < 0.001) were elevated in DM-CKD compared with DM-only. S + E reduced sCD40L in DM-CKD patients (P = 0.01), but LLT did not influence VWF or elastase. CONCLUSIONS:DMpatients withCKD stages 3-4 had increased PLA and inflammatory activity compared with DMpatients with normal GFR. Simvastatin + ezetimbe decreased PLAs and plasma sCD40L in DM patients with concomitant CKD. Clinical Trial registration http://www.clinicaltrials.gov. Identifier NCT01035320.
RCT Entities:
BACKGROUND:Diabetes mellitus (DM) is associated with hyperreactive platelets and increased platelet-leukocyte aggregation (PLA), but the impact of concomitant chronic kidney disease (CKD) has been much less studied. Lipid-lowering treatment (LLT) may have favorable effects on platelet activation and inflammation. The objective of this mechanistic study was to investigate the impact of CKD on platelet function and inflammatory parameters in patients with DM and the effects of LLT. METHODS: After a placebo run-in period, the effects of simvastatin alone (S) or simvastatin + ezetimibe (S + E) were compared in a randomized, double-blind, cross-over study on platelet reactivity, PLA formation and inflammatory parameters. Eighteen DMpatients with estimated glomerular filtration rate (eGFR) 15-59 mL/min × 1.73 m(2) (CKD stages 3-4) (DM-CKD) and 21 DMpatients with eGFR >75 mL/min (DM-only) were included. RESULTS: PLAs were elevated at baseline in DM-CKD compared with DM-only (P = 0.04). S + E reduced PLAs among total leukocytes and neutrophils in DM-CKDpatients (P = 0.01 for both) but not in the DM-only group. Platelet reactivity did not differ between patient groups or with LLT. Plasma levels of sCD40L (P < 0.001), elastase (P < 0.01) and von Willebrand factor (VWF) (P < 0.001) were elevated in DM-CKD compared with DM-only. S + E reduced sCD40L in DM-CKDpatients (P = 0.01), but LLT did not influence VWF or elastase. CONCLUSIONS:DMpatients with CKD stages 3-4 had increased PLA and inflammatory activity compared with DMpatients with normal GFR. Simvastatin + ezetimbe decreased PLAs and plasma sCD40L in DMpatients with concomitant CKD. Clinical Trial registration http://www.clinicaltrials.gov. Identifier NCT01035320.
Authors: Caroline Pereira Domingueti; Luci Maria S Dusse; Rodrigo Bastos Fóscolo; Janice Sepúlveda Reis; Joyce Maria Annichino-Bizzacchi; Fernanda Loureiro de Andrade Orsi; Bruna de Moraes Mazetto; Maria das Graças Carvalho; Karina Braga Gomes; Ana Paula Fernandes Journal: PLoS One Date: 2015-07-13 Impact factor: 3.240