Serum hepatocyte growth factor is associated with viral hepatitis, cardiovascular disease, erythropoietin treatment, and type of heparin in haemodialysis patients

Abstract

Background. Increased serum hepatocyte growth factor (HGF) level is a part of the counter-system against tissue damage and predicts mortality in maintenance haemodialysis (HD) patients. We studied which of the common co-morbid and clinical conditions, and surrogates of metabolic disorders or specific organ damage determine HGF levels in these subjects. Methods. In 86 patients, pre-dialysis serum HGF, soluble endothelial markers-such as thrombomodulin (TM), von Willebrand factor and plasminogen activator inhibitor-1-and hepatitis B and C markers were measured by ELISAs. Inflammatory reactants such as C-reactive protein (CRP), α1-antitrypsin, α1 acid-glycoprotein, and immunoglobulin M and G were assayed by nephelometry, and lipoprotein(a) was determined by ELISA. Cardiovascular disease (CVD) was identified on a clinical basis. Results. Serum HGF was directly associated with the presence of viral hepatitis, alanine aminotransferase and TM levels, time on HD, the presence of CVD, CRP and α1-antitrypsin levels, use of unfractionated heparin (UFH) (vs enoxaparin) during HD, dose of UFH, use of recombinant erythropoietin (rHuEpo) treatment, and Kt/V. In 36 patients not treated with rHuEpo, HGF directly correlated with haemoglobin, but not with endogenous Epo levels. There was no association between HGF and the other endothelial and inflammatory markers, gender, age, smoking, cause of renal failure, body mass index, normalized protein catabolic rate, dialysate buffers, dialysers, blood pressure, antihypertensive treatment, leukocyte and platelet counts, albumin, fibrinogen, lipoprotein(a), markers of iron and calcium-phosphorus metabolism, or metabolic acidosis. Positive viral hepatitis markers, prevalent CVD and rHuEpo treatment (in descending order of significance) were independent predictors of high HGF level. In another 20 HD patients, a 4-week course of rHuEpo treatment resulted in a significant 17% increase in circulating HGF levels. Conclusion. Serum HGF levels in HD patients are determined by inflammatory conditions such as viral hepatitis and CVD, increase in response to rHuEpo treatment, and may be influenced by type and dose of heparin used during HD procedures.