Hepatocyte growth factor predicts survival and relates to inflammation andintima media thickness in end-stage renal disease

Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in tissue protection and repair in the endothelium and various organ systems. The se rum concentration of this protein is markedly increased in patients with ch ronic renal diseases, but the clinical and pathophysiological correlates of this substance in renal failure are scarcely understood, Serum HGF, lipid, albumin, hemoglobin, C-reactive protein (CRP), and immunoglobulin G (IgG) were measured in fasting conditions in a cohort of 244 dialysis patients. I n addition, the relationship between HGF and severity of carotid atheroscle rosis was studied in a subgroup of 105 patients. The entire cohort was foll owed up for a median of 31 months (interquartile range, 21 to 34 months). S erum HGF level was directly related to duration of dialysis treatment, CRP level, age, IgG level, and hemoglobin level and inversely related to systol ic and diastolic arterial blood pressure, In a multiple regression model, o nly duration of dialysis treatment (r = 0.38), age (r = 0.26), hemoglobin l evel (r = 0.17), IgG level (r = 0.15), and CRP level (r = 0.14) were indepe ndent correlates of serum HGF level (R = 0.54; P < 0.0001), suggesting that increased levels of serum HGF may be the expression of a chronic inflammat ory process. HGF levels were greater in hemodialysis than continuous ambula tory peritoneal dialysis patients, independent of the type of dialysis memb rane, and slightly increased in patients seropositive for hepatitis C virus . In the subgroup of patients who underwent echo color Doppler studies, ser um HGF level was an independent correlate of intima media thickness (IMT; p artial r = 0.23; P = 0.02). In the entire cohort, increased HGF levels pred icted shorter survival in a multivariate Cox regression model. These result s support the hypothesis that in patients with chronic renal failure, incre ased serum HGF level is linked to an inflammatory state. The relationships between HGF level and survival and IMT suggest that this cytokine might be a marker of a process that has a major impact in the high mortality and mor bidity of the dialysis population. (C) 2000 by the National Kidney Foundati on, Inc.