TY - JOUR
T1 - Chronic renal failure is accompanied by endothelial activation and a large increase in microparticle numbers with reduced procoagulant capacity
AU - Trappenburg, Marijke C.
AU - van Schilfgaarde, Muriel
AU - Frerichs, Fenneke C. P.
AU - Spronk, Henri M. H.
AU - ten Cate, Hugo
AU - de Fijter, Carola W. H.
AU - Terpstra, Wim E.
AU - Leyte, Anja
PY - 2012/4
Y1 - 2012/4
N2 - Background. In patients with chronic renal failure (CRF), cardiovascular disease is the leading cause of increased morbidity and mortality. We hypothesized a role for endothelial activation and microparticle (MP) numbers and procoagulant activity in the pre-thrombotic state of these patients. Methods. We analysed blood samples of 27 patients with CRF [8 chronic kidney disease Stage 4 (CKD4), 9 peritoneal dialysis (PD) and 10 haemodialysis (HD), samples taken before and after HD] and 10 controls. Degree and nature of endothelial activation were assessed by measuring mature von Willebrand factor (vWF) and vWF propeptide levels. Cellular MPs were characterized by flow cytometry and MP-specific thrombin generation (TG) measurements. Results. CRF was accompanied by chronic (CKD4 and PD) or acute (HD) endothelial activation. Patients with CRF had substantially higher MP numbers than controls (median 9400 versus 4350 3 10(6)/L, P = 0.001), without significant differences between the treatment subgroups or between pre- and post-HD. The vast majority of MPs were platelet derived. Of the minor populations, endothelial MPs and tissue factor-bearing MPs were more abundant in CRF. MPs were procoagulant, but the increase in numbers was not reflected in a proportional increase in MP-specific TG. Conclusion. Renal failure is accompanied by endothelial activation of a different nature in CKD4 and PD patients compared to HD patients, and results in all subgroups in an increase of mainly platelet-derived MPs that appear to be less procoagulant than in other disease states, possibly because of the uraemic functional defect of their cellular source.
AB - Background. In patients with chronic renal failure (CRF), cardiovascular disease is the leading cause of increased morbidity and mortality. We hypothesized a role for endothelial activation and microparticle (MP) numbers and procoagulant activity in the pre-thrombotic state of these patients. Methods. We analysed blood samples of 27 patients with CRF [8 chronic kidney disease Stage 4 (CKD4), 9 peritoneal dialysis (PD) and 10 haemodialysis (HD), samples taken before and after HD] and 10 controls. Degree and nature of endothelial activation were assessed by measuring mature von Willebrand factor (vWF) and vWF propeptide levels. Cellular MPs were characterized by flow cytometry and MP-specific thrombin generation (TG) measurements. Results. CRF was accompanied by chronic (CKD4 and PD) or acute (HD) endothelial activation. Patients with CRF had substantially higher MP numbers than controls (median 9400 versus 4350 3 10(6)/L, P = 0.001), without significant differences between the treatment subgroups or between pre- and post-HD. The vast majority of MPs were platelet derived. Of the minor populations, endothelial MPs and tissue factor-bearing MPs were more abundant in CRF. MPs were procoagulant, but the increase in numbers was not reflected in a proportional increase in MP-specific TG. Conclusion. Renal failure is accompanied by endothelial activation of a different nature in CKD4 and PD patients compared to HD patients, and results in all subgroups in an increase of mainly platelet-derived MPs that appear to be less procoagulant than in other disease states, possibly because of the uraemic functional defect of their cellular source.
KW - chronic renal failure
KW - microparticles
KW - thrombin generation
KW - tissue factor
KW - von Willebrand factor
U2 - 10.1093/ndt/gfr474
DO - 10.1093/ndt/gfr474
M3 - Article
C2 - 21873622
SN - 0931-0509
VL - 27
SP - 1446
EP - 1453
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 4
ER -