HEMODIALYSIS STIMULATES HEPATOCYTE GROWTH-FACTOR RELEASE

Studies were performed in 26 patients on regular dialysis treatment wi th cuprophane (CU), polymethylmetacrilate (PMMA) or cuprammonium (CAM) dialyzers. Controls were sis patients with chronic renal failure but not on regular dialysis treatment (CRF) and six healthy subjects (N). Blood was collected at the start (T-0), and at 15 (T-151 and 240 (T-24 0) minutes of dialysis to measure the serum hepatocyte growth factor ( HGF) concentration and to study HGF production by peripheral blood mon onuclear cells (PBMC) in vitro. The form of HGF (that is, inactive/mon omeric, active/dimeric) present in the serum was analyzed by immunoblo tting. 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 T-0, serum HGF levels were identical to that of t he controls. In patients treated with CU, serum HGF rose from 0.24 ng/ ml at T-0 to 7.44 ng/ml at T-15, and remained high at T-240. PBMC coll ected at T-15 and T-240 released significantly more HGF in vitro than those collected at T-0. Serum at T-15 stimulated proliferation of HK-2 cells and the release of HGF by PBMC and MRC-5 cells. The PMMA and CA M dialyzers had similar effects as the CU. These results indicate that dialysis induces a striking rise in serum HGF and a prompt circulatio n of factor(s) stimulating HGF release. Dialysis-activated PBMC releas e HGF.