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

Abstract

Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in tissue protection and repair in the endothelium and various organ systems. The serum concentration of this protein is markedly increased in patients with chronic 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. In addition, the relationship between HGF and severity of carotid atherosclerosis was studied in a subgroup of 105 patients. The entire cohort was followed up for a median of 31 months (interquartile range, 21 to 34 months). Serum HGF level was directly related to duration of dialysis treatment, CRP level, age, IgG level, and hemoglobin level and inversely related to systolic and diastolic arterial blood pressure. In a multiple regression model, only duration of dialysis treatment (r = 0.38), age (r = 0.26), hemoglobin level (r = 0.17), IgG level (r = 0.15), and CRP level (r = 0.14) were independent 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 inflammatory process. HGF levels were greater in hemodialysis than continuous ambulatory peritoneal dialysis patients, independent of the type of dialysis membrane, and slightly increased in patients seropositive for hepatitis C virus. In the subgroup of patients who underwent echo color Doppler studies, serum HGF level was an independent correlate of intima media thickness (IMT; partial r = 0.23; P = 0.02). In the entire cohort, increased HGF levels predicted shorter survival in a multivariate Cox regression model. These results support the hypothesis that in patients with chronic renal failure, increased 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 morbidity of the dialysis population.