Raquel Ojeda

Effects of intravenous iron on mononuclear cells during the haemodialysis session

BACKGROUNDnThis study analysed, in vivo and in vitro, the effects of four different intravenous iron preparations (iron gluconate, iron sucrose, iron dextran and ferric carboxymaltose) on activation and damage of mononuclear cells.nnnMETHODSnA randomized prospective study was conducted in 10 haemodialysis (HD) patients. Blood samples were collected at baseline (T0); 1 h after starting HD, just before the iron or saline administration (T1); 30 min after the iron or saline infusion (T2) and at the end of HD (T3). In addition, peripheral blood mononuclear cells from 10 healthy individuals and 9 chronic kidney disease Stage-5 (CKD-5) without HD treatment were cultured with the 4 iron preparations.nnnRESULTSnIron infusion during the HD session increased the percentage of mononuclear cells with reactive oxygen species (ROS) production, Inter-Cellular Adhesion Molecule-1 (ICAM-1) and apoptosis. There were no significant differences between the four iron preparations. Culture of mononuclear cells from healthy individuals and CKD-5 patients with the different iron preparations resulted in a significant increase in ROS, ICAM-1 and apoptosis as compared with control. In an additional study, the effect of original iron sucrose formulation on mononuclear cells was compared with that of one generic formulation. The generic formulation produced a greater increase in ROS, ICAM-1 and apoptosis than the original iron sucrose.nnnCONCLUSIONSnOur results suggest that intravenous iron has deleterious effects on mononuclear cells. The four iron compounds evaluated produced similar effects on oxidative stress, cell activation and apoptosis. However, the effects of iron compounds with the same formulation were different, thus further investigation may be required to establish the safety of iron preparations that theoretically have the same composition.

Microinflammation and endothelial damage in hemodialysis.

BACKGROUNDnChronic kidney disease (CKD) stage 4-5 patients have increased cardiovascular morbidity and mortality rates compared with the general population. Chronic inflammation has been proposed as a cardiovascular risk factor. We have previously demonstrated that the majority of CKD patients show a microinflammatory state with an increased percentage of CD14+/CD16+ monocytes in peripheral blood, even in patients who do not show clinical evidence of inflammatory disease. However, the role played by these microinflammatory cells on the endothelial damage that precede the development of cardiovascular disease has not been investigated.nnnMETHODSnTo study the effect of microinflammation on endothelial cell injury we have developed an experimental co-culture model in which isolated CD14+/CD16+ cells were seeded in 24-well tissue-culture plates. Human umbilical vein endothelial cells were placed on the top of the culture well in a insert that permitted intercellular soluble network communication. To stimulate the release of proinflammatory products, monocytes were activated with substimulating doses of bacterial DNA. Endothelial injury was characterized measuring intracellular reactive oxygen species activity and cell apoptosis.nnnRESULTSnOnly CD14+/CD16+ cells released proinflammatory cytokines when they were stimulated by bacterial DNA. In the culture wells in which inflammatory cytokines were detected, endothelial cells showed an increased reactive oxygen species activity and features of apoptosis.nnnCONCLUSIONSnOur results support the hypothesis that independently of uremia, in CKD stage 4-5 patients microinflammation mediated by CD14+/CD16+ cells induces endothelial damage and thus may contribute to the increased risk of atherosclerosis and cardiovascular disease that has been reported in this population.

Effect of Different Dialysis Modalities on Microinflammatory Status and Endothelial Damage

BACKGROUND AND OBJECTIVESnWe studied the relationship between microinflammation and endothelial damage in chronic kidney disease (CKD) patients on different dialysis modalities.nnnDESIGN, SETTING, PARTICIPANTS, & MEASUREMENTSnFour groups of CKD stage 5 patients were studied: 1) 14 nondialysis CKD patients (CKD-NonD); 2) 15 hemodialysis patients (HD); 3) 12 peritoneal dialysis patients with residual renal function >1 ml/min (PD-RRF >1); and 4) 13 peritoneal dialysis patients with residual renal function <or=1 ml/min (PD-RRF <or=1). Ten healthy subjects served as controls. CD14(+)CD16(+) cells and apoptotic endothelial microparticles (EMPs) were measured by flow cytometry. Serum vascular endothelial growth factor (VEGF) was measured by ELISA.nnnRESULTSnCKD-NonD and HD patients had a higher percentage of CD14(+)CD16(+) monocytes than PD groups and controls. CD14(+)CD16(+) was similar in the PD groups, regardless of their RRF, and controls. The four uremic groups displayed a marked increase in apoptotic EMPs and VEGF compared with controls. Apoptotic EMPs and VEGF were significantly higher in HD patients than in CKD-NonD and both PD groups. However, there were no significant differences between CKD-NonD and the two PD groups. There was a correlation between CD14(+)CD16(+) and endothelial damage in CKD-NonD and HD patients, but not in PD and controls.nnnCONCLUSIONSnThere was an increase in CD14(+)CD16(+) only in CKD-NonD and HD patients. In these patients, there was a relationship between increased CD14(+)CD16(+) and endothelial damage. These results strongly suggest that other factors unrelated to the microinflammatory status mediated by CD14(+)CD16(+) are promoting the endothelial damage in PD, regardless of their RRF.

CD14+CD16+ monocytes from chronic kidney disease patients exhibit increased adhesion ability to endothelial cells.

Chronic kidney disease (CKD) patients present an inflammatory process that induces endothelial damage and therefore plays a role in the high rates of cardiovascular morbidity and mortality reported in these patients. Although new therapies have reduced the elevated serum levels of inflammatory mediators such as cytokines and CRP in CKD patients, the rise in the level of activated immunocompetent cells is maintained in peripheral blood, which appears to play a prominent role in the endothelial damage suffered by these patients. CD14+CD16+ monocytes are a subset of activated monocytes that are found in greater numbers in the peripheral blood of CKD patients. The increased presence of these cells is related to the endothelial damage suffered by these patients. However, the mechanism through which these cells damage the vascular endothelium is still unclear. One of the characteristics that differentiate CD14+CD16+ monocytes is their powerful ability to produce inflammatory cytokines, which may be responsible for causing damage to endothelial cells. However, it is difficult to imagine that the cytokines produced by a relatively small proportion of these cells are capable of damaging the endothelium. For this reason, we have suggested that these cells do not release their cytokines into the bloodstream, but that they possess cellular mechanisms that lead them to produce and release cytokines after adhering to the layer of endothelial cells. This hypothesis is based on the fact that unlike the CD14++CD16- monocytes found in healthy subjects, CD14+CD16+ monocytes in CKD patients show a high level of expression of chemokines that favors their migration to the vascular wall, and a low level of chemokines such as CCR2 that would prevent such migration. Furthermore, these CD14+CD16+ monocytes express a large number of adhesion molecules, which helps them attach to endothelial cells. In view of this scenario, it is easy to suggest that a moderate number of CD14+CD16+ monocytes might well be capable of producing endothelial damage; therefore, the rise in the number of these cells in CKD patients may play an important role in the development of vascular disease.

Tandem Plasmapheresis and Hemodialysis: Efficacy and Safety

Background: Hemodialysis (HD) and plasmapheresis (PE) are usually performed independently on patients who require renal replacement therapy. We analyzed our experience using a technique that performs both modalities simultaneously. Methods: Thirty-six patients who were treated with 287 tandem PE and HD (TPH) sessions (mean 7.97 ± 5.6 per patient) were included. PE was connected 30 min after HD started. The mean HD blood flow was 313.7 ± 44 mL/min, the mean PE blood flow was 141 ± 25 mL/min, and the duration of TPH was no longer than 240 min. The heparin dose was similar to that used for a standard HD procedure. Results: In 287 TPH sessions performed, 10.45% experienced minor complications. There were significant changes in mean blood pressure after connection of the PE system. However, these differences were not clinically relevant since patients remained asymptomatic and they did not require saline infusion. At the end of treatment, 38.9% of patients were no longer dependent on dialysis. Conclusions: Our results suggest that TPH is a safe and effective treatment that decreases exposure to an extracorporeal circuit, reducing the risks that are associated with anticoagulation agents and improving the comfortability of the patient.

Bioimpedance Spectroscopy as a Practical Tool for the Early Detection and Prevention of Protein-Energy Wasting in Hemodialysis Patients

OBJECTIVESnTo evaluate whether body composition monitor (BCM) could be a practical instrument for nephrologists to assess nutritional status in patients on hemodialysis (HD) and whether it is more effective in identifying patients at highest risk of developing protein-energy wasting (PEW) alone or in combination with other tools currently used for that purpose.nnnDESIGNnObservational cross-sectional study in 91 HD patients (60xa0±xa014xa0years, 70.3% male, 24xa0±xa04.1xa0kg/m2 body mass index) from 2 different locations.nnnMETHODSnNutritional status was evaluated by anthropometric methods (biceps and triceps skinfold thickness, waist circumference, and arm muscular circumference), biochemical nutritional markers, malnutrition-inflammation score (MIS), and BCM. The patients were grouped into those with and without PEW by using classical criteria and then classified as being adequately or inadequately nourished according to a BCM flow chart to detect those requiring preferential nutritional intervention. A multivariate approach was used to calculate the risk of developing PEW.nnnRESULTSnAnthropometric measurements revealed significantly lower body mass index (<23xa0kg/m2; odds ratios [OR]xa0=xa013.3 and Pxa0=xa00.001) and arm muscular circumferencexa0<xa0p10 (ORxa0=xa034, Pxa0<xa00.001) in the PEW group. MIS was above 5 in all the patients classified as having PEW. BCM showed that fat tissue index < p10 was significantly lower in this group (ORxa0=xa01.52), and a decision tree using the lean tissue index < p10, fat tissue indexxa0<xa0p10, and extracellular waterxa0>xa015% revealed that 42.9% of the patients would need nutritional monitoring. On multivariate analysis, insufficient nutritional status detected by BCM decision tree was an independent prognostic factor for developing PEW. About 9.89% of the patients were classified as PEW, with MIS > 5, and insufficient nutritional status detected by BCM required preferential nutritional intervention.nnnCONCLUSIONnBCM is a practical instrument for nephrologists to assess nutritional status in patients on HD and is useful for the early prevention and detection of PEW, as is able to identify differences in body composition, predict clinically important outcomes, and classify patients requiring preferential nutritional intervention.

Elimination of hepatitis C virus infection from a hemodialysis unit and impact of treatment on the control of anemia

INTRODUCTIONnIn the interferon era, the treatment of hepatitis C virus (HCV) infection in patients on haemodialysis (HD) was limited due to the significant number of treatment-related adverse events (AEs). Direct-acting antivirals (DAAs) have demonstrated their efficacy and safety in the treatment of HCV in patients with advanced chronic kidney disease on haemodialysis. The objective of the study was to evaluate the success in eliminating HCV infection from our dialysis unit using DAAs, and to assess the impact of HCV elimination on clinical and analytical outcomes.nnnPATIENTS AND METHODSnThis is a prospective, interventional, single-center study at Hospital Clínic de Barcelona. All HCV-RNA positive patients who received antiviral therapy with DAAs within a 3-year period (2014-2017) were analyzed (n=20). Data on virologic response, adverse events, and biochemical and hematological parameters during and after DAA therapy were analyzed.nnnRESULTSnAll patients achieved sustained virologic response (SVR) and only 40% of patients presented with mild AEs. None of the patients presented with HCV reinfection after a 1-year follow-up period, and thus HCV was eliminated from our HD unit. SVR was associated with a significant increase in hemoglobin and hematocrit, and a tendency toward the need for lower doses of iron supplementation with no changes in darbepoetin dose.nnnCONCLUSIONnHCV infection can be safely eliminated from HD units with the use of DAAs, preventing new infections in patients and healthcare staff. In the short term, the achievement of SVR is associated with an improvement in the control of anemia.