Soluble thrombomodulin is associated with viral hepatitis, blood pressure,and medications in haemodialysis patients

Background. The level of soluble thrombomodulin (sTM), a traditional marker of endothelial injury, is also dependent on renal excretory function. We s tudied serum sTM in chronic haemodialysis (HD) patients to determine which factors are predictive of its levels in this population. Methods and results. sTM levels of 10.7 (5.72-30.7) ng/ml in 100 HD patient s were higher than in 30 controls (P < 0.0001). In a bivariate regression a nalysis, immunoreactive sTM was positively associated with the presence of hepatitis B virus surface antigen and/or anti-hepatitis C virus antibodies measured by third generation ELISAs (P < 0.0001), and was related to certai n markers of liver injury and biosynthetic dysfunction. sTM was also direct ly associated with time on dialysis (P = 0.001), or use of unfractionated h eparin (UFH) (vs enoxaparin) (P = 0.0007), erythropoietin (P = 0.008), ACE- inhibitors (P = 0.034), acetate-buffered dialysate (vs bicarbonate) (P = 0. 040), pre-dialysis systolic (P = 0.012), and diastolic blood pressure (P = 0.043). It was negatively associated with lipoprotein(a) (P = 0.029). sTM w as not related to age, sex, smoking, cause of renal failure, prevalence of cardiovascular disease, amount of HD delivered, preserved residual renal fu nction, ferritin, C-reactive protein, and other vasoactive medications used . In a multivariable analysis, a positive hepatitis marker (P = 0.0002), th e use of UFH (P = 0.030) and erythropoietin (P = 0.019), and raised pre-dia lysis blood pressure (P = 0.034) were positive independent predictors of hi gh sTM level. Conclusion. Those data indicate that, in addition to endothelial activation , elevated sTM levels in HD patients may be related to viral infection and/ or liver dysfunction, and influenced by modifiable factors such as increase d blood pressure, and the type of heparin and erythropoietin treatment used .