Hepatocyte growth factor in saliva of patients with renal failure and periodontal disease.

BACKGROUND: Hepatocyte growth factor (HGF), endogenous cytokine with pleiotropic repairing and regeneration properties in relation to most tissues and organs, contributes to the progression of periodontal disease (PD). Furthermore, PD is a significant health problem in patients with chronic renal failure (CRF). The role of HGF in the development of PD in this specific population was not a subject of research so far. MATERIAL AND METHODS: The following groups were enrolled in the study: (1) 26 chronic hemodialysis (HD) subjects, (2) 26 patients treated by continuous ambulatory peritoneal dialysis (CAPD), (3) 28 predialysis CRF patients, (4) 26 subjects with advanced PD (without coexisting diseases), and (5) 20 healthy subjects without PDs. HGF level in saliva was measured using the immunoenzymatic method. Gingival index, papillary bleeding index, plaque index, and the loss of clinical attachment level were evaluated. RESULTS: The HGF level in saliva of HD patients was twice higher than in that of subjects with healthy periodontium. Direct relationships between proper HGF level in saliva and the indices GI, PBI, and PI in CAPD-treated patients and with more severe PD were shown. It was found that PD is most advanced in HD patients, moderately in CAPD-treated patients and to the smallest extent in predialysis CRF patients. CONCLUSIONS: The HGF level in mixed saliva is the index of PD progression in subjects without renal failure and in CAPD-treated patients. PD is common in renal failure patients and is a significant problem concerning general health status.

[Salivary phosphate-binding chewing gum--an integrative approach to chronic kidney disease and oral diseases]. / Guma do zucia wiazaca fosforany--jednoczesne leczenie przewleklej choroby nerek i chorób jamy ustnej.

The course and treatment of chronic kidney disease (CKD) is adversely affected by numerous metabolic disarrangements, comorbid states and general diseases, i.e. hyperphosphatemia and metabolic bone disease, chronic inflammation, accelerated atherosclerosis (partly of infectious etiology) and devastating cardiovascular disease. Furthermore, CKD patients are usually afflicted by multiple oral abnormalities, including troublesome oral dryness and the very aggressive form of periodontal disease. The use of chitosan-containing chewing gum in CKD subjects seems to offer a novel therapeutic approach of interdisciplinary importance: the chitosan binds salivary phosphates and, when swallowed, likely phosphates in the alimentary tract, thus beneficially lowering blood phosphate levels, while the gum itself increases impaired salivary flow and has a potent oral antimicrobial activity. Thus, it effectively improves general oral hygiene and prevents progression of periodontal disease being (besides of hyperphosphatemia) one of the established causes of atherosclerosis development/progression. The undemanding maneuver of chewing the chitosan-containing, phosphate-binding gum has a potential to diminish excessive morbidity in CKD patients.

Pleiotropic effects of heparin and heparinoids in peritoneal dialysis.

Unfractionated heparin, low-molecular-weight heparins, and sulodexide belong to the family of glycosaminoglycans. Recent studies report on properties other than anticoagulant activities of these medications. They include modulation of cell growth and proliferation via actions on numerous growth factors affecting the immune system and matrix molecules production and degradation. Long-term peritoneal dialysis remarkably influences peritoneal cavity homeostasis by mechanisms mediated by growth factors. They initiate progression of pathological processes and further account for morphological and functional alterations of the peritoneal membrane. The best-recognized pathologies in peritoneal cavity under these conditions encompass inflammation, fibrosis, and vasculopathy, often leading to fatal encapsulating peritoneal sclerosis. Intraperitoneal heparin and its derivatives, by their pleiotropic actions, may influence these crucial processes and improve the peritoneal dialysis technique survival in a complex and so far understudied way. These issues, novel medical approaches, and their likely mechanisms have been reviewed.

Hepatocyte growth factor/activin A/follistatin system activation during hemodialysis with different low molecular weight heparins.

Hepatocyte growth factor (HGF), activin A (Act A), and follistatin (FS) compose an organotrophic system; interestingly it is modified by heparin. To understand if LMWHs (considered distinct drugs) have different clinical profiles regarding the above growth factors, we studied the effects of enoxaparin, nadroparin, and dalteparin on their plasma levels. Seventeen chronic HD patients completed this prospective, crossover trial. They were randomized into six groups: each patient was administered enoxaparin (effective dose of 0.75 mg/kg), nadroparin (70.4 IU/kg) and dalteparin (78.6 IU/kg) in three time periods of two months each. At the end of this period, the cytokine's plasma levels were measured by immunoassays at the start and at 10 min and 180 min of the HD procedure. At 10 min, we observed a striking increase in plasma HGF (32-fold), Act A (4-fold), and FS (53%), all p = 0.0003. The levels of HGF and Act A remained markedly elevated after 180 min (by 295% and 87%, respectively; both p < 0.002), while those of FS returned to baseline. There were no differences in cytokine profile comparing both their peak concentrations and the areas under the curve. Enoxaparin, dalteparin, and nadroparin are seemingly not different considering the release of HGF/Act A/FS during HD procedures; this may reflect their similar profile in other aspects. Moreover, the concentrations of HGF/Act A/FS are close to therapeutic ones, which may partly explain the mechanisms underlying some of the emerging extra-anticoagulant effects of LMWHs.

Chronic viral hepatitis C, oxidative stress and the coagulation/fibrinolysis system in haemodialysis patients.

INTRODUCTION: The aim of the present study was to establish whether the presence of chronic viral hepatitis (PVH) could be implicated in the elevation of oxidative stress (SOX) and haemostasis system in haemodialysis (HD) patients. MATERIALS AND METHODS: In HD patients with and without PVH and in controls we compared the markers of: coagulation pathway- tissue factor (TF) and its inhibitor (TFPI), prothrombin fragment F (1+2) (F (1+2)); fibrinolysis: tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA) and its soluble receptor (suPAR), plasminogen activator inhibitor 1 (PAI-1), plasmin/antiplasmin complexes (PAP); and a marker of SOX-Cu/Zn superoxide dismutase (Cu/Zn SOD) levels. RESULTS: Patients, particularly those with PVH, showed a significant increase in the markers of the coagulation, fibrinolysis and oxidative status as compared to controls. All parameters of coagulation/fibrinolysis system were directly associated with the PVH and Cu/Zn SOD levels, and there was a relationship between the PVH and Cu/Zn SOD levels. Multivariable analysis showed that PVH and increased SOX were identified as independent variables significantly associated with the disturbances of coagulation/fibrinolysis system in these patients. CONCLUSIONS: We concluded that PVH is a novel determinant of the increased oxidative stress as well as the disturbances of coagulation/fibrinolysis system in haemodialysis patients.

Effects of Enoxaparin on Intravascular Sclerostin Release in Healthy Men.

Sclerostin (Scl) is implicated in vascular calcification and angiogenesis and localizes within vasculature. Its molecule incorporates a heparin-binding site that implies also binding to endothelial glycocalyx. We preliminary tested whether intravenous (IV) low-molecular-weight heparin enoxaparin can stimulate intravascular release of this calcification inhibitor in humans. Sixteen male volunteers were injected with a bolus of 1 mg/kg body weight of enoxaparin. After 10 minutes, plasma immunoreactive Scl levels increased uniformly by a mean of 184% versus baseline level of 0.56 ± 0.17 ng/mL ( P = .0004). Plasma Scl levels were found still elevated after 2 and 6 hours (with a median of 20.9% and 8.69%, respectively) and became normal after 24 hours. The percentage of increase (Δ) in plasma Scl after 10 minutes was directly correlated with enoxaparin dose per kg/m2 of body mass index (ρ = 0.587, P = .017) and strongly inversely correlated with the preinjection Scl levels (ρ = -0.747, P = .0008). A robust negative association between the ΔScl increase after 10 minutes and the ΔScl decrease after 2 hours versus 10 minutes was observed (ρ = -0.835, P < .0001). Complementary in vitro spiking experiment showed no effects of enoxaparin addition and whole blood incubation on plasma Scl levels when measured with the immunoassay. This study shows that enoxaparin has a stimulating effect on the intravascular release of calcification inhibitor Scl in healthy men. This novel pharmacological action of the popular anticoagulant drug seems important in cardiovascular medicine.

Sulodexide induces hepatocyte growth factor release in humans.

Heparin influences numerous pleiotropic growth factors, including hepatocyte growth factor (HGF), partially by their release from endothelial and extracellular matrix stores. The effects of sulodexide, a heparin-like glycosaminoglycan medication of growing importance in medicine, on HGF liberation are not known. We performed a 2-week open-label sulodexide trial in healthy male volunteers. The drug was initially administered intravenously (i.v.) in a single dose of 1200 Lipoprotein Lipase Releasing Units (LRU), then -- orally for 12 days (500 LRU twice a day), and -- again by i.v. route (1200 LRU) on day 14. Intravenous sulodexide injections were repeatedly found to induce marked and reproducible increases in immunoreactive plasma HGF levels (more than 3500% vs baseline after 10 min, and more than 1200% after 120 min), and remained unchanged when measured 120 min following oral sulodexide administration. The percentage increments in plasma HGF evoked by i.v. sulodexide at both time points and on both days inversely correlated with baseline levels of the growth factor. On day 14, the HGF levels after 120 min and their percentage increase vs baseline were strongly and directly dependent on i.v. sulodexide dose per kg of body weight. This study shows that sulodexide has a novel, remarkable and plausibly biologically important stimulating effect on the release of pleiotropic hepatocyte growth factor in humans.

Sulodexide for hemodialysis anticoagulation in heparin-induced thrombocytopenia type II.

Heparin-induced thrombocytopenia type II (HIT II) is an immune-mediated prothrombotic state. It requires cessation of all forms of heparin exposure. In maintenance hemodialysis (HD) patients, alternative anticoagulants (i.e. bivalirudin, danaparoid, fondaparinux) may be tried for HD procedure anticoagulation. Sulodexide (SLX) - a purified glycosaminoglycan preparation (80% heparan sulfate and 20% dermatan sulfate) - is not neutralized by platelet factor 4 and may be useful in HIT II. A 32-year-old man on continuous ambulatory peritoneal dilaysis (CAPD) and with protracted atrial fibrillation was given enoxaparin prophylaxis. On day 4, his platelets dropped from 119,000/micronL to 27,000/micronL and HIT II was diagnosed by positive heparin-induced platelet aggregation. While enoxaparin was withdrawn, the platelet count increased and remained stable. In the meantime, atrial fibrillation subsided but the patient developed pseudomonal peritonitis; the catheter was removed and the patient was switched to HD with SLX as an anticoagulant (bolus of 30 mg at HD onset). He was uneventfully treated with HD for 6 weeks and then reverted to CAPD. The widely available and inexpensive SLX may be a new, effective and potentially promising alternative anticoagulant in HD patients with HIT II.

Unexpected and striking effect of heparin-free dialysis on cytokine release.

Heparin (both unfractionated and low molecular weight) is not only a potent anticoagulant but also has many pleiotropic effects, some of which are mediated by cytokine release. We compared the effect of hemodialysis (HD) with enoxaparin as an anticoagulant and without systemic anticoagulation (heparin-grafted membrane-Evodial) on the release of monocyte chemoattractant protein 1 (MCP-1), endostatin (ES) and activin A (Act-A). Nineteen stable HD patients were dialyzed with or without heparin, and plasma levels of MCP-1, ES and Act-A were measured after such a dialysis. During HD with Evodial, the intradialytic levels of all three cytokines were 2-3 folds lower. The between-anticoagulant differences were significant over time for all three cytokines: MCP-1 (P < 0.001), ES (P < 0.001) and Act-A (P < 0.001). This striking effect of heparin-free dialysis with Evodial membrane may be beneficial not only because it reduces the possibility of bleeding complications but also because it might reduce proinflammatory cytokine concentration and therefore contribute to the improvement in endothelial function. Further studies are needed to determine whether it has a positive effect on morbidity and mortality of maintenance HD patients.

Myeloperoxidase as a marker of hemodialysis biocompatibility and oxidative stress: the underestimated modifying effects of heparin.

Myeloperoxidase (MPO) is a microbicidal and reactive species-generating enzyme. It traditionally is considered to be stored mostly within polymorphonuclear leukocytes and is strongly implicated in the pathogenesis of numerous diseases. MPO also has been studied for at least 20 years as a marker of hemodialysis procedure biocompatibility and oxidative stress generation; research yielded discordant and inconclusive results. In this review, a novel and growing body of evidence indicating that MPO also is a potent blood vessel-bound enzyme that can be mobilized rapidly and extensively into circulating blood by exogenous heparin is discussed. Beneficial consequences of such evoked arterial wall MPO depletion that may be counterbalanced in part by the harmful effects of circulating MPO on polymorphonuclear leukocyte activation and thus atherosclerosis propagation also are presented. Potential clinical implications of these undervalued phenomena in commonly atherosclerotic maintenance hemodialysis patients regularly administered large doses of heparin for temporary blood anticoagulation (frequently over years) are stressed, including the challenging issue of morbidity and mortality. In view of the plausible clinical importance of the novel MPO-oxidative stress-heparin interaction in this population, the need for additional studies assessing different dialyzer membranes, various heparin types (unfractionated heparin versus low-molecular-weight heparins versus pentasaccharides), as well as different anticoagulation regimens, is emphasized.

Hepatocyte growth factor in saliva is a potential marker of symptomatic periodontal disease.

Evidence has been emerging that hepatocyte growth factor (HGF) - a pluripotential regenerative cytokine - is a key factor in the pathogenesis and progression of periodontal disease, mostly through its over-stimulation of gingival epithelial cell growth and impairment of the regeneration of collagenous structures. We measured the levels of immunoreactive HGF in unstimulated whole mixed saliva from 26 patients referred for treatment of periodontal disease, and from 20 healthy subjects. HGF was detected in all saliva samples from the patients, the concentration ranging from 0.06 to 5.38 ng/ml, with a mean concentration of 1.87 +/- 1.32 ng/ml. In healthy individuals, the median salivary HGF level was 0.68 ng/ml (range: 0 - 7.33 ng/ml), being almost 3-fold lower (P < 0.0001) than that in the patients. Periodontal parameters in the patients were: gingival index (GI) 2.0 (0 - 2.8), papillary bleeding index (PBI) 2.2 (0 - 3.2), plaque index (PI) 2.0 (0 - 3.0), probing depth (PD) 3.0 (1.8 - 5.9) mm, and loss of clinical attachment level (CAL) 4.7 (1.1 - 10.6) mm. We found that the salivary HGF level was positively correlated with GI (P = 0.004), PBI (P = 0.046) and PI (P = 0.001), but not with PD (P = 0.351), CAL loss (P = 0.172), number of teeth (P = 0.279) or patient age (P = 0.362). Our findings suggest that salivary HGF concentration may be a novel marker of symptomatic periodontal disease, and that it warrants further validation.

[Relevance of some growth factors to cardiovascular disease in maintenance hemodialysis patients]. / Niektóre czynniki wzrostowe a choroby ukladu krazenia u pacjentów hemodializowanych.

Hepatocyte growth factor, activin A and follistatin compose an intricate, pleiotropic and mostly antagonistic cytokine network. They have a crucial impact on the cardiovascular system, including the development of atherosclerosis and its ischemic complications. We reviewed the significance of the above growth factors in maintenance hemodialysis patients, and stressed their likely causative role in the acceleration of cardiovascular disease progression. Recent clinical trials showing marked activation of the growth factors by heparin administered during hemodialysis procedures also were discussed, including the distinct effects of unfractionated heparin vs low-molecular-weight heparin enoxaparin.

[SEN virus infection in maintenance hemodialysis patients]. / Zakazenie wirusem sen u pacjentów przewlekle hemodializowanych.

SEN virus (SENV) is a new, mostly parenterally transmitted, hepatotropic agent. The prevalence of SENV among patients undergoing maintenance hemodialysis (HD) in Poland, as well as risk factors for the infection are not established. Serum samples of 91 patients receiving maintenance HD in Bialystok were tested for the presence of strain H SENV (SENV-H) DNA by means of polymerase chain reaction. Fifty-one non-dialysis subjects, age- and sex-matched with the HD patients, mostly with chronic kidney diseases (96%), without hepatitis B (HBV) and C (HCV) or the history of blood transfusion and donation served as controls. SENV-H viremia was prevalent in 40% of HD patients and in 2% of control subjects (p < 0.0001). On multivariable logistic analysis, neither age (63.1 +/- 13.2 years), gender (49% females), dialysis vintage (29, 2-200, months), previous transfusions of packed red blood cells (84%) or fresh frozen plasma (4%), seropositivity for HBs antigen (13%), HCV antibodies (23%) or HCV RNA (17%) were independently associated with SENV-H prevalence in HD patients (chi2 for the model = 13.3, p = 0.103). No associations between SENV-H status and clinical or biochemical markers of liver disease, including serum aminotransferases levels were observed. In conclusion, SENV-H viremia is widespread among patients receiving maintenance HD in north-eastern Poland. Risk factors for its occurrence are equivocal; the infection may well be transmitted by parenteral and feco-oral routes. SEN virus is not directly responsible for liver damage in maintenance HD patients.

[Evaluation of the thyroid size among school children aged 6-13 with the normal iodine excretion in the urine and the usability of referential values still applied]. / Ocena wielkosci tarczycy w populacji dzieci szkolnych w wieku 6-13 lat z prawidlowym wydalaniem jodu z moczem a przydatnosc stosowanych dotychczas wartosci referencyjnych.

BACKGROUND: The evaluation criteria of the enlarged thyroid gland becomes a key problem when analyzing the prevalence of goiter in the population of school children. The review of the literature and own experience indicate lack of a consensus concerning this problem among researchers. Similarly, in the report of WHO in the year 2001 concerning the problem of iodine deficit and goiter endemia, experts did not present universal referential values of the thyroid size in ultrasonography for children population aged 6-15 years living in the regions of proper iodine supply in the diet, thus suggesting the necessity of working out regional norms. OBJECTIVES: The aim of the study was to evaluate the prevalence of goiter in children aged 6-13 years from schools chosen randomly in Bialystok with proper iodine supplementation in the study population and to estimate the usability of referential values applied in the assessment of the thyroid size. MATERIAL AND METHODS: In the year 2002, the examination was carried out in 4 elementary schools chosen randomly from Bialystok. A total of 480 children aged 6-13 years were included in the study. All children were examined physically with palpation assessment of the thyroid size and had USG of the thyroid. The concentration of iodine was measured in the morning urine. The blood samples were collected to determine hTSH concentration. RESULTS: In palpation, with regard to WHO criteria of the year 2001, the prevalence of goiter was 6.8% in the study population. Applying WHO criteria of 1994 in palpation assessment of goiter increased this percentage up to 18.2%. When using WHO criteria for body surface of 1997 to evaluate goiter by USG, its percentage equaled 7%, whereas taking into consideration referential values for child's age doubled its percentage up to 13.5%. The percentage of goiter increased up to 45.5%, when referential values introduced by Gutekunst et al. were applied. CONCLUSIONS: When evaluating the thyroid size in ultrasonographic diagnostics of goiter in children aged 6-13 years, it seems more purposeful to apply referential values of the thyroid size regarding the body surface and sex (manifesting a child's actual physical development) than to use the norms concerning the calendar age. The prevalence of goiter amounting 7% in the population of school children in spite of adequate iodine prophylaxis suggests other than iodine deficit, factors causing goiter in this population.

Relationship between oxidative stress and extrinsic coagulation pathway in haemodialyzed patients.

Enhanced oxidative stress (SOX), endothelial dysfunction and haemostatic abnormalities are common in end-stage renal failure patients undergoing maintenance haemodialysis (HD). We studied associations among circulating immunoreactive total lipid peroxides as a marker of short-time SOX, autoantibodies against oxidized LDL as a surrogate of prolonged SOX, copper/zinc superoxide dismutase (Cu/Zn SOD) as a major antioxidant enzyme, tissue factor (TF) as a principal initiator of extrinsic coagulation pathway counteracted by its inhibitor (TFPI), and prothrombin fragment 1+2 (F 1+2) as a surrogate of activated haemostasis.Pre-dialysis blood levels of all the markers studied were higher in 24 clinically stable HD patients compared to 11 healthy controls. Spearman's correlations among the three SOX markers were positive but nonsignificant in both HD patients and controls. In HD subjects, increased Cu/Zn SOD levels directly correlated with those of TF (rho=0.551, p=0.005) and TFPI (rho=0.501, p=0.001); the coagulation markers were also positively associated with each other (rho=0.663, p=0.0004). In healthy subjects, the relations between Cu/Zn SOD, TF and TFPI levels were inverse but not significant, and the direct association between TF and TFPI was nonsignificant either. In conclusion, increased plasma levels of Cu/Zn SOD, the antioxidant enzyme with emerging endothelial cell-protective and antithrombotic properties, may be a novel part of the system counteracting activated extrinsic coagulation system in maintenance HD patients.

Effects of recombinant erythropoietin therapy on circulating endothelial markers in hemodialysis patients.

Effects of a 4-week course of recombinant human erythropoietin (rHuEpo) therapy on four circulating endothelium-derived cardiovascular risk markers were studied in 20 patients receiving maintenance hemodialysis in relation to surrogates of chronic inflammation, liver function, and arterial blood pressure. Soluble intercellular adhesion molecule-1 (sICAM-1), antigens of plasminogen activator inhibitor-1 (PAI-1:Ag) and von Willebrand factor (vWF:Ag), and soluble thrombomodulin (sTM) were determined by immunoenzymatic assays. C-reactive protein; alpha1 acid-glycoprotein; alpha1-antitrypsin; immunoglobulin M, A, and G; interleukin-6; lipoprotein(a); fibrinogen; total protein; albumin; total cholesterol; hepatitis B and C markers; liver enzymes; prothrombin time; and phosphorus were measured by routine methods. The rHuEpo treatment resulted in a 25% increase in sICAM-1 (Wilcoxon's p = 0.001), a 50% increase in PAI-1:Ag (p = 0.004), a 15% increase in sTM (p = 0.002), and did not change vWF:Ag levels. The increase in sICAM-1 concentration directly correlated with that of PAI-1:Ag (Spearman's rho = 0.483, p = 0.031). The rHuEpo-induced increases in hemoglobin, platelets, and pre-dialysis diastolic blood pressure levels did not correlate with the increments in the endothelial markers studied. In conclusion, short-term rHuEpo therapy activates vascular endothelium in patients receiving maintenance hemodialysis. This specific effect may influence cardiovascular risk.

Tissue factor and thrombomodulin in hemodialysis patients: associations with endothelial injury, liver disease, and erythropoietin therapy.

Patients receiving maintenance hemodialysis (HD) present with hemostatic abnormalities, which may be aggravated by comorbid conditions, especially liver disease. The factors that influence plasma levels of thrombomodulin (TM), an initiator of the anticoagulant protein C pathway, and those of tissue factor (TF), which triggers the extrinsic coagulation pathway, were assessed. In 63 HD patients, TM and TF levels were higher than those in healthy controls. In bivariate analysis, TF positively correlated with TM, and both were directly associated with the presence of viral hepatitis B or C marker, serum liver enzymes, use of erythropoietin therapy, hemoglobin levels, and duration of HD therapy, and inversely correlated with body mass index. TF was also positively associated with plasma von Willebrand factor (vWF) antigen, and inversely associated with activated partial thromboplastin time. In multivariate analysis, increased vWF, alanine aminotransferase, and use of erythropoietin independently predicted both TF and TM levels. HD patients with vWF and ALT levels lower than middle, and not treated with erythropoietin had normal TF but increased TM concentrations compared with levels in healthy controls. Increased plasma levels of TM and TF in patients on maintenance HD are surrogates of vascular endothelial injury. Liver disease and use of erythropoietin treatment are also important determinants of these markers, and should be considered in further studies.

Effect of hemodialysis on plasma levels of vascular endothelial markers.

Vascular endothelial cell dysfunction is linked to hemostatic abnormalities and accelerated atherosclerosis in patients receiving maintenance hemodialysis (HD). The relationships between pre-dialysis plasma levels of immunoreactive thrombomodulin, von Willebrand factor, tissue factor and its inhibitor were studied, and the effects of HD procedure on these endothelial markers were observed. All the markers were higher in 39 HD patients than in 15 healthy controls (p<0.0001). HD treatment resulted in a 50% increase in tissue factor pathway inhibitor (p<0.0001), but did not influence the other markers. This increment directly correlated with the post-dialysis decrease in diastolic (p=0.011) and mean arterial blood pressure (p=0.039), and the surface area of the dialysis membrane (p=0.007). There were no associations between the increase in tissue factor pathway inhibitor and the amount of fluid removed, dose of enoxaparin, or other HD-specific factors. In conclusion, HD is responsible for an increase in plasma tissue pathway factor inhibitor level. The release of tissue factor pathway inhibitor during HD is not only due to heparin injection but also to the contact between blood and artificial dialysis membrane, and to HD-activated hemodynamic forces.

Endothelial injury markers with high-dose intravenous iron therapy in renal failure.

Endothelial injury is prevalent in patients with chronic renal failure (CRF) and may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline, administered over 1 hour, median treatment duration 5 days) on circulating endothelium and/or tissue injury markers such as hepatocyte growth factor, thrombomodulin, von Willebrand factor, and C-reactive protein levels were studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre-dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined absolute and/or functional iron deficiency. The measurements were performed before iron administration and 24 hours after the last infusion. All the markers remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic or other adverse effects were observed. In conclusion, the above high-dose IV iron sucrose supplementation does not cause evident endothelial or other tissue injury in patients with CRF, and is clinically safe.

Effects of enoxaparin on myeloperoxidase release during hemodialysis.

Myeloperoxidase (MPO) is a proteolytic and prooxidant enzyme largely assembled with the vascular wall, and a heparin-binding protein. We studied if low-molecular-weight heparin enoxaparin administered for hemodialysis (HD) anticoagulation causes systemic MPO activation. Plasma MPO levels were measured in patients undergoing maintenance HD with an intravenous bolus of enoxaparin. Patients were retested during HD employing dialyzers with heparin-grafted polyacrylonitrile membrane and no systemic enoxaparin administration. During enoxaparin-anticoagulated HD plasma MPO levels strikingly increased in all patients (8.6-fold at 10 minutes and 3.3-fold at 120 minutes, both P < 0.0001). The increments were directly associated with the enoxaparin dosage and strongly inversely with the predialysis levels of the enzyme. The increase in plasma MPO during systemic heparin-free HD was significantly less pronounced. Enoxaparin administered for HD anticoagulation induces a marked and dose-dependent increase in plasma MPO as a plausibly favorable result of the liberation of the enzyme from the vascular wall.