Minutes Of Hemodialysis Research Articles

P1435RELATIONSHIP BETWEEN INTRA-DIALYTIC OXYGEN EXTRACTION RATIO (OER) CHANGE AND IDH

Abstract Background and Aims Intradialytic hypotension (IDH) involves a reduced tolerance to hemodialysis (HD), a poor quality of life and is associated with mortality. Intradialytic monitoring systems (blood pressure, heart rate, volemia) are not able to identify patients at greater risk of IDH. IDH is a hemodynamic phenomenon and attention has recently been given to the evaluation of oxygen saturation to evaluate its role in IDH. Oxygen Extraction Ratio (OER), the ratio between SaO2 and ScvO2, is a parameter used to monitor parenchyma oxygen consumption and stress. Recent evidence showed that HD patients with a greater delta OER (ΔOER) during HD (threshold 40%)had higher mortality risk. OER could be a new monitoring instrument to measure hemodialysis induced sub-clinical parenchyma hypoxia and stress, two elements included in the pathogenesis of IDH. The aim of the study was to evaluate the relationship between OER and IDH incidence. Method Inclusion criteria: age ≥18 years, chronic HD treatment by means of permanent jugular CVC, no evidence of acute underlying illness. We evaluated OER ([(SaO2 − ScvO2)/SaO2] × 100) before HD and at 15’, 30’, 60’ and post HD in three HD sessions (HD OER sessions). For the statistic analysis we considered for each patient the median OER value obtained from the three HD OER sessions. Then we started the follow-up study with a minimum follow-up of three months and end follow-up of two years, to record IDH (defined according to K/DOQI guidelines) for each patient. We divided the population in two groups using as a threshold the median percentage number of IDH in our population and evaluate the differences between the obtained two groups in pre HD OER, Delta OER and intradialytic OER trends. Results During the follow-up period (mean 12 ± 1.2 months), we enrolled 28 patients with permanent jugular CVC: 13 males and 15 females, aged 74±2.6 years, HD vintage 46 ± 6.5 months. The HD OER sessions for each patient were asymptomatic. Pre HD OER was 34 ± 1.4, post HD OER 46 ± 1.8, with a Delta OER of 39 ± 5 %. OER change during HD was evident since after 15 minutes (OER% 15’: 40 ± 1.2 p<.001) and continued to increase progressively (OER% end HD 46 ± 1.8; p<.0001). During the follow up period we monitored 4342 HD sessions of which 186 with IDH, the median incidence of IDH was 3.6% of all HD sessions. We divided patients into two groups based on the median value of IDH incidence: (IDH % ≤ 3.6 and IDH % > 3.6). The two groups were not different for age (76 ± 2.4 vs 73 ± 3.0 years; p <ns), HD vintage (52 ± 8.6 vs 40 ± 4.0 months; p <ns), systolic (125 ± 3.2 vs 129 ± 4.0 mmHg; p <ns) and diastolic blood pressure (67 ± 2.2 vs 70 ± 2.2 mmHg; p <ns) and heart rate (70 ± 2.2 vs. 76 ± 2.3 bpm; p <ns) (Tab. 2). The IDH % >3.6 group had 159 IDH out of a total of 1911 sessions (9%), while IDH % ≤ 3.6 group had 27 IDH out of 2431 sessions (0.9%). Pre HD OER values were not different between the groups while the IDH % >3.6 group had greater delta OER% than the IDH % ≤ 3.6 group (43 ± 4.8 vs. 35 ± 3.0 %; p <.05) (Figure). Evaluating the OER trend during HD session a higher ΔOER% was found at 15 minutes of HD treatment in the IDH % > 3.6 group (ΔOER 20± 3.0 % vs. 8.0 ± 3.0 %; IDH % > 3.6 group vs. IDH % ≤ 3.6 group, p <.05), data confirmed at 30' (24 ± 3.0 % vs. 13 ± 5.0 %; p <.05), and post HD (43 ± 5.0 % vs 35 ± 3.0 %; p <.05), but not at 60 minutes of HD treatment (19 ± 4.0 % vs. 17 ± 4.6 %; p <ns). Conclusion Our data show that intradialytic ΔOER, representative of the extent of tissue hypoxic stress, identifies patients at greater risk of IDH. In particular, a ΔOER of 20% after the first 15 minutes of HD and of 43% at the end of the HD session characterizes the more hemodynamically fragile patients. The measurement of the OER can be a new and easy monitoring instrument to identify the most hemodynamically fragile patients already after the first 15 minutes of HD treatment.

Different Effects of Enoxaparin, Nadroparin, and Dalteparin on Plasma TFPI During Hemodialysis

Low-molecular-weight heparins (LMWHs) are an alternative to unfractionated heparin (UFH) for anticoagulation during hemodialysis (HD). We performed a prospective randomized crossover study of the effect of enoxaparin, nadroparin, and dalteparin on some hemostatic factors, including tissue factor pathway inhibitor (TFPI), in patients with maintenance HD. Plasma levels (immunoassays) of total TFPI, platelet-derived growth factor-AB (PDGF-AB), and prothrombin fragment 1 + 2 (PF 1 + 2) were evaluated pre-HD, after 10 (T10) and 180 (T180) minutes of HD in 21 patients, who completed a 3-period (for 2 months each) crossover study in 6 groups (Latin-square design). The baseline TFPI, PDGF-AB, and PF 1 + 2 levels were comparable under all LMWH treatments. Tissue factor pathway inhibitor levels, compared with the baseline, significantly increased (all P < 10(-4)), whereas PDGF-AB levels remained stable at each interval during enoxaparin, nadroparin, and dalteparin anticoagulated HD. Interestingly, TFPI increment at T10 was the highest, dose-dependent, and accompanied by PF 1 + 2 decrease under enoxaparin administration. The switch from enoxaparin to nadroparin and dalteparin used as anticoagulants had no long-term effect on the baseline total TFPI and PF 1 + 2 levels in chronically HD patients. Only short-term, overdialytic differences were noticed, indicating a single bolus of enoxaparin (0.75 mg/kg) as the most potent stimulus for endothelial TFPI.

Unfractionated Heparin but Not Enoxaparin Causes Delayed Plasma PAI-1 Depletion in Hemodialysis Patients: A Prospective Study

Heparin modulates function of vascular endothelial cells. We studied the effects of unfractionated heparin (UFH) versus low-molecular-weight heparin (LMWH), enoxaparin, used as anticoagulants during hemodialysis (HD) on plasma levels of circulating endothelium-derived molecules: thrombomodulin (TM), von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), cell surface adhesion molecules (E-selectin), intercellular adhesion molecule-1 (ICAM-1), and prothrombin fragment 1+2 (PF 1+2). Twenty-five patients undergoing enoxaparin-anticoagulated HD were randomly assigned either to continue enoxaparin (n = 13) or receive UFH (n = 12) during HD and followed prospectively for 12 weeks. Plasma immunoreactive TM, vWF, PAI-1, ICAM-1, E-selectin, and PF 1+2 were measured before the randomization procedure and after 12 weeks, at the start, after 10 and 180 minutes of HD. The switch from LMWH to UFH resulted in decreased pre-HD levels of PAI-1 and TM and increased PF 1+2 concentrations. Predialysis PAI-1 negatively correlated with the total dose of UFH/kg/HD. No significant differences were observed in the other variables before and during HD after switching from LMWH to UFH. During enoxaparin-anticoagulated HD, only plasma PAI-1 levels decreased by 32% after 180 minutes compared with the baseline values. This percentage decrease positively correlated with predialysis PAI-1 levels and marginally with PF 1+2 concentrations after 180 minutes of enoxaparin-anticoagulated HD. Enoxaparin-anticoagulated HD is related to transient plasma PAI-1 decrease, whereas UFH anticoagulation may be the cause of delayed PAI-1 and TM depletion, which is an untoward consequence of enhanced coagulation activity in chronic HD patients.

Influence of Parenteral Iron Therapy and Oral Vitamin E Supplementation on Neutrophil Respiratory Burst in Chronic Hemodialysis Patients

Background. Bioincompatibility of hemodialysis (HD) membranes is responsible for neutrophil activation leading to oxidative stress, which can be further increased by intravenous (IV) iron (Fe) administration. The aim of our study was to monitor neutrophil respiratory burst during HD and to find out whether this process is influenced by IV Fe and oral vitamin E administration. Methods. Within four HD sessions, blood samples were taken from seven chronic HD patients at time 0 (before HD), 60, 70, and 130 min of HD session. Neutrophil respiratory burst was assessed by luminol-enhanced chemiluminescence (CL). Plasma advanced oxidation protein products (AOPP) concentration was measured spectrophotometrically. During the second and the fourth HD, 62.5 mg of sodium ferric gluconate was applied IV in the 65th minute of HD. Before the last two HD, the patients were given orally 200 mg of vitamin E daily for 7 days. Patient's results were compared with healthy controls. Results. Predialysis CL is higher in patients than in controls (1,926 ± 436 vs. 1,083 ± 325 RLU, p < .01). CL decreases in the 60th min of HD (1,926 ± 436 vs. 1,220 ± 599 RLU, p < .05); thereafter, it remains stable. After Fe application, CL increases at time 130 compared with CL at time 60 (1,303 ± 269 vs. 877 ± 292 RLU, p < .05). AOPP concentration is higher in patients than in controls (137.5 ± 42.7 vs. 88.9 ± 24.8 µmol/L, p < .01) and remains unaffected by vitamin E supplementation. After vitamin E intake, predialysis CL remains significantly higher than in controls, and changes in CL during HD are minimal despite Fe administration. Conclusion. HD patients' neutrophils generate more oxygen radicals than in healthy individuals. This production decreases during HD and then increases after IV Fe administration. Short-term vitamin Eadministration attenuates this fluctuation of neutrophil oxidative metabolism, without affecting the total degree of oxidative stress.

Anaphylactoid reactions during hemodialysis on AN69 membranes in patients receiving ACE inhibitors

We report five life-threatening anaphylactoid reactions occurring within the very first minutes of hemodialysis on polyacrylonitrile (AN69) capillary dialyzers in three patients receiving ACE inhibitors. Such reactions were not observed either in patients treated with ACE inhibitors but dialyzed on other membranes (N = 9), nor in patients on AN69 who did not receive ACE inhibitors (N = 19). These anaphylactoid reactions could be due to bradykinin accumulation, as a result of both increased synthesis--by interaction of blood with the AN69 polymer--and catabolism blockade by ACE inhibitors.

Plasma DNA in patients undergoing hemodialysis or hemofiltration: cytolysis in artificial kidney is responsible for the release of DNA in circulation.

Levels of circulating DNA increase under treatment by an artificial kidney. Using a new assay, levels of plasma DNA are studied in 45 patients during 99 sessions of hemodialysis or hemofiltration. Before the session, plasma DNA levels are increased in 41/99 samples and, among them, in 18/24 samples collected from hepatitis B surface antigen carriers. During the first 3 h of the session, plasma DNA levels increase whatever the method of treatment. At the 30th and 60th minute of hemodialysis, a positive gradient of plasma DNA exists between the output and the input of the artificial kidney. It is concluded that: (1) the increase in plasma DNA is related to the overall procedure of artificial kidney therapy; (2) death of leukocytes in the artificial kidney is responsible for the release and the increase in circulation of extracellular DNA.

Hemodialysis with calcium-free dialysate prevents myocardial creatine kinase depletion after brief coronary artery occlusion in dogs.

To evaluate the effect of hypocalcemia on myocardial creatine kinase (CK) depletion after brief coronary artery occlusion and reperfusion, dogs were rendered hypocalcemic via systemic hemodialysis for eighty minutes in the absence of Ca. Control animals were hemodialysed in the presence of Ca. The left anterior descending coronary artery was then occluded for six minutes and reperfusion for eighty minutes occurred at low flow of dialysate. A 50% decrease in serum Ca of the hypocalcemic animals during the eighty minutes of hemodialysis resulted in a significant (about 35%) decrease of myocardial Ca. Comparison of the myocardial creatine kinase activity following reperfusion showed preservation of the enzyme in the ischemic areas of the hypocalcemic animals, whereas the CK activities of the ischemic areas of the normocalcemic animals were much lower (p less than 0.005). During the reperfusion period serum Ca of the hypocalcemic group increased to 75% of that of the normocalcemic group while myocardial Ca of both ischemic and nonischemic areas reequilibrated to normocalcemic values. Hemodynamic parameters during the various phases of the experiment were not altered significantly. It is concluded that transient decrease of myocardial Ca produced by hypocalcemia prior to occlusion leads to protection against myocardial damage after brief coronary ligation.

Influence of hemodialysis on plasma chemotactic activity and the chemotactic responsiveness of polymorphonuclear neutrophils.

Thirty patients with chronic renal failure on maintenance hemodialysis (HD) were studied. Plasma chemotactic activity was estimated using the "under agarose" chemotaxis assay during the first 2 h of HD. It was found that in the fifth minute of HD, patients' plasma became chemotactic, reaching the maximum activity at the tenth minute. The chemotactic activity appearance correlated significantly with the decline in the number of the peripheral neutrophils. Patients' neutrophils, after a single passage through the cellophane coil of the dialyzer, revealed significant impairment of directed migration toward both complementary and bacterial chemoattractants. Moreover, the chemotactic properties of neutrophils obtained from dialyzed patients before HD were significantly lower than had been estimated in 15 nondialyzed patients with chronic renal failure. The results confirm HD-induced complement activation and might explain the mechanisms of the increased susceptibility of dialyzed patients to bacterial infections.

Studies of the plasma factor which induces augmented granulocyte adherence during hemodialysis.

Transient granulocytopenia develops during the first few minutes of hemodialysis, and is associated with a marked increase in granulocyte adherence as the cells marginate in the pulmonary circulation. The increased adherence is mediated by factors present in the plasma, thought to be complement components activated by the dialysis coil. In the present study, an assay of plasma for adherence-augmenting activity shows that it is maximal at 15 min after starting dialysis, and undetectable at 40 min. The factor is not affected by heating to 56 degrees C for 30 min, or by incubation at 37 degrees C for 7 days, nor does dialysis for 24 h against physiologic saline diminish its activity. However, exposure to pH 6.0 reduces the activity to 58.4% of control, and pH 5.0 reduces it to 40.1%. Finally, pretreatment of patients with prednisone before hemodialysis does not prevent granulocytopenia or increased adherence. These findings are discussed in relation to the known properties of various biologically active fragments of complement.