Hemodialysis stimulates hepatocyte growth factor release

Abstract

Studies were performed in 26 patients on regular dialysis treatment with cuprophane (CU), polymethylmetacrilate (PMMA) or cuprammonium (CAM) dialyzers. Controls were six patients with chronic renal failure but not on regular dialysis treatment (CRF) and six healthy subjects (N). Blood was collected at the start (T0), and at 15 (T15) and 240 (T240) minutes of dialysis to measure the serum hepatocyte growth factor (HGF) concentration and to study HGF production by peripheral blood mononuclear cells (PBMC) in vitro. The form of HGF (that is, inactive/monomeric, active/dimeric) present in the serum was analyzed by immunoblotting. In addition, the ability of serum to stimulate proliferation of tubular cells (HK-2) and HGF release by PBMC and fibroblasts (MRC-5) was investigated. At T0, serum HGF levels were identical to that of the controls. In patients treated with CU, serum HGF rose from 0.24 ng/ml at T0 to 7.44 ng/ml at T15, and remained high at T240. PBMC collected at T15 and T240 released significantly more HGF in vitro than those collected at T0. Serum at T15 stimulated proliferation of HK-2 cells and the release of HGF by PBMC and MRC-5 cells. The PMMA and CAM dialyzers had similar effects as the CU. These results indicate that dialysis induces a striking rise in serum HGF and a prompt circulation of factor(s) stimulating HGF release. Dialysis-activated PBMC release HGF.

Hepatocyte Growth Factor and Left Ventricular Geometry in End-Stage Renal Disease

“…[13][14][15][16] HGF has a short half-life and is cleared mainly by the liver. 14 Although the precise mechanism(s) responsible for the high levels of serum HGF in ESRD are still unclear, it appears that this phenomenon does not represent the mere effect of reduced removal of this substance by the diseased kidneys.…”

“…11,12 Therefore, ESRD is an interesting natural model to explore the relation between serum HGF and the cardiovascular system. Studies have reported that this cytokine is markedly raised in patients with ESRD [13][14][15][16] and may be considered a novel vascular modulator in humans. 17,18 Of note, we previously reported that serum HGF in ESRD correlated with carotid intima-media thickness, thus behaving as a marker of atherosclerosis.…”

Hepatocyte Growth Factor in Saliva of Patients with Renal Failure and Periodontal Disease

“…[12][13][14][15][16][17][18][19][20][21][22] The role of growth factors in the pathogenesis of PD in CRF patients was not subject to research so far. Systemic activation of the HGF/c-Met system generally found in these patients, 8,[21][22][23][24][25][26][27] in particular under the influence of heparin administrated for the purpose of anticoagulation of blood during HD treatments, [25][26][27] may be a significant element in the development and progression of PD.…”

Elevated Hepatocyte Growth Factor Levels at the Beginning of High-Flux Hemodialysis Are Due to Heparin Administration

“…[3] Moreover, it has been reported that hemodialysis stimulates HGF release. [4] F. Christidou et al…”

“…Soluble heparin molecules can bind and replace HGF from heparin sulphate proteoglycans on the cell surface [4,5] and in the extracellular matrix. By this process, heparin administration induces an immediate rise of circulating serum HGF levels.…”