Department of Nephrology
and Internal Medicine
Medical Academy
Biaystok, Poland
Email: jborawski{at}post.pl
Sir,
Hepatocyte growth factor (HGF) is a multipotent cytokine of growing importance in tissue development, apoptosis, regeneration and repair of injuries. In chronic haemodialysis (HD) patients, serum HGF levels are increased, directly related to the extent of arteriosclerosis and chronic inflammation, and the prevalence of cardiovascular disease and viral hepatitis, and may stimulate erythropoiesis [1,2]. They also independently predict mortality in dialysis patients [2]. Increased HGF may thus be viewed as a marker of co-morbidity and poor survival, and at the same time as an indicator of the activated body repair in this population.
Recently, we reported in this journal that the use of unfractionated heparin (UFH) vs low molecular weight (LMW) enoxaparin during intermittent HD could be directly predictive of increased serum HGF levels [1]. We also found a direct association between pre-dialysis levels of the cytokine and a dose of UFH. Therefore, we hypothesized that heparin could be a specific stimulus for the HGF release in maintenance HD patients [1]. In the present study, we followed serum HGF levels during dialysis [by enzyme-linked immunosorbent assay (ELISA) from R&D Systems, Inc., Minneapolis MN] in 14 patients anticoagulated with enoxaparin (Clexane, Bellon Rhône-Poulenc Rorer, Montrouge, France). The heparin was injected into the arterial line as a bolus of 40 (2060) mg (0.70 ± 0.22 mg/kg) at the onset of HD, following the initial rinse of the circuit with 1000 ml of isotonic saline containing 2.0 IU/ml of UFH. The anticoagulation regimen had been employed effectively for at least 2 months prior to the study.
Serum HGF levels were 1.82 (1.205.70) ng/ml pre-dialysis, 31.0 (15.483.7) ng/ml after 10 min, and 8.97 ± 3.56 ng/ml after 180 min from the start of HD and after enoxaparin injection (Friedmans ANOVA 2 for the change = 28.0, P < 0.0001). As shown in Figure 1A, HGF strikingly increased by a mean of 1596 ± 650% after 10 min of HD compared with baseline (Wilcoxons P = 0.001). After 180 min, it was higher by 349 ± 190% vs pre-dialysis, and lower vs the 10 min level (both P = 0.001). The 10 min percentage increase in HGF (Spearmans
= 0.594, P = 0.025, Figure 1B) but not that at 180 min (
= 0.268, P = 0.353) significantly correlated with the dose of enoxaparin.
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Our data show for the first time that the early increase in serum HGF directly depends on the dose of enoxaparin used for blood anticoagulation during intermittent HD procedures. It implies that heparin may be a modulator of the biological effects of HGF in chronic HD patients, especially as the cytokine also acts as a classic hormone exerting its distant effects in a concentration-dependent manner. The consequences of such marked and prolonged elevations in serum HGF due to repeated heparin administration may be important in HD patients. They deserve further detailed evaluation because HGF augments organ repair but may also propagate cancer metastases due to its angiogenic effects.
References