Biomedical subjects

Marion Morena

Publications and source records attributed to Marion Morena.

10 recordsLinked to original sources

PubMed2006

Overview of clinical studies in hemodiafiltration: what do we need now ?

Despite several technical advances in dialysis treatment modalities and a better patient care management including correction of anemia, suppression of secondary hyperparathyroidism, lipid and oxidative stress profiles improvement, the morbidity and the mortality of dialysis patients still remain still elevated. Recent prospective interventional trials in hemodialysis (HEMO study and 4D study) were not very conclusive in showing any significant improvement in dialysis patient outcomes. High-efficiency convective therapies, such as online hemodiafiltration (HDF), are claimed to be superior to conventional diffusive hemodialysis (HD) in improving the dialysis efficacy and in reducing intradialytic morbidity and all-cause and cardiovascular mortality in dialysis patients. The aim of this report was, first, to review the evidence-based facts tending to prove the superiority of HDF vs. HD in terms of efficacy and tolerance, and, second, to analyze the needs to prove the clinical superiority of HDF in terms of reducing morbidity and all-cause mortality of dialysis patients. A systematic review of studies comparing HDF and HD has been performed in the microbiological safety of online production, the solute removal capacity of small and medium-size uremic toxins, and its implication in the reduction of the bioactive dialysis system vs. patient interaction. Major planned randomized international studies comparing HDF and HD in terms of morbidity and mortality have been reviewed. To conclude, it is thought that these long-term prospective randomized trials will clarify on a scientific evidence-based level the putative beneficial role of high-efficiency HDF modalities on dialysis patient outcomes.

Cardiovascular Diseases↗

PubMed2005

Plasma osteoprotegerin is associated with mortality in hemodialysis patients.

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Regulating molecules such as osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) could play a key role in bone-vascular calcification imbalance. This study investigated the contribution of these proteins as well as mineral metabolism disorders in hemodialysis (HD) patient outcome. A total of 185 HD patients were followed up prospectively for 2 yr. In addition to clinical characteristics, mineral metabolism markers as well as OPG and soluble RANKL (sRANKL) were measured at baseline. After 2 yr, survival rates were described with Kaplan-Meier and compared with Cox regression analyses; 50 patients died (27 from cardiovascular diseases). Calcium, phosphate, and calcium x phosphate product were not associated with mortality. Both hyperparathyroidism (parathyroid hormone > or =300 pg/ml) and hypoparathyroidism (parathyroid hormone <150 pg/ml) were poorly associated with all-cause and cardiovascular mortality. By contrast, elevated OPG levels predicted all-cause (relative risk [RR] 2.67; 95% confidence interval [CI] 1.32 to 5.41; P = 0.006) and cardiovascular mortality (RR 3.15; 95% CI 1.14 to 8.69; P = 0.03). Low levels of sRANKL were associated with a protective effect for all-cause mortality (RR 0.45; 95% CI 0.21 to 0.94; P = 0.03). The association of OPG with all-cause mortality was stronger in patients with C-reactive protein > or =12.52 mg/L. In this condition, both highest (RR 5.68; 95% CI 1.48 to 22.73; P = 0.01) and lowest tertiles (RR 5.37; 95% CI 147 to 1968; P = 0.01) significantly predicted poor outcome. These results show that regulating-bone molecules, especially OPG, are strong predictors of mortality in HD patients, suggesting that OPG is a vascular risk factor, in particular in patients who have high C-reactive protein levels. OPG determination therefore should be added to the biologic follow-up of these patients.

Adult↗

PubMed2005

Overproduction of reactive oxygen species in end-stage renal disease patients: a potential component of hemodialysis-associated inflammation.

During the past decade, hemodialysis (HD)-induced inflammation has been linked to the development of long-term morbidity in end-stage renal disease (ESRD) patients on regular renal replacement therapy. Because interleukins and anaphylatoxins produced during HD sessions are potent activators for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an example of an enzyme that is responsible for overproduction of reactive oxygen species (ROS), this may constitute a link between leukocyte activation and cell or organ toxicity. Oxidative stress, which results from an imbalance between oxidant production and antioxidant defense mechanisms, has been documented in ESRD patients using lipid and/or protein oxidative markers. Characterization of HD-induced oxidative stress has included identification of potential activators for NADPH oxidase. Uremia per se could prime phagocyte oxidative burst. HD, far from improving the oxidative status, results in an enhancement of ROS owing to hemoincompatibility of the dialysis system, hemoreactivity of the membrane, and trace amounts of endotoxins in the dialysate. In addition, the HD process is associated with an impairment in antioxidant mechanisms. The resulting oxidative stress has been implicated in long-term complications including anemia, amyloidosis, accelerated atherosclerosis, and malnutrition. Prevention of oxidative stress in HD might focus on improving the hemocompatibility of the dialysis system, supplementation of deficient patients with antioxidants, and modulation of NADPH oxidase by pharmacologic approaches.

Anaphylatoxins↗

PubMed2004

Superoxide anion overproduction in sepsis: effects of vitamin e and simvastatin.

Oxidative stress during sepsis induces tissue damage, leading to organ dysfunction and high mortality. The antioxidant effects of vitamin E have been reported in several diseases, but not in sepsis. Statins have cholesterol-independent anti-inflammatory effects that are related to a decrease of isoprenoid proteins and oxidative stress. Therefore, we evaluated superoxide anion (O2- degree) production and ex vivo effects of vitamin E and simvastatin in sepsis. Fourteen healthy volunteers, 14 intensive care unit (ICU) nonseptic, and 14 ICU patients with sepsis were included in this prospective study. Plasma cholesterol, triglyceride, and vitamin E levels were determined by routine laboratory tests. Superoxide anion production was measured in the venous blood by chemiluminescence technique after phorbol myristate acetate stimulation. Effects of vitamin E and simvastatin on O2- degree production was investigated ex vivo. Luminescence was indexed to the leukocyte count. We also investigated the in vitro effect of simvastatin on translocation of NADPH oxidase p21 Rac2 subunit in THP-1 monocytic cell line. The ratio of vitamin E/cholesterol + triglycerides was significantly decreased in septic as compared with nonseptic patients and volunteers. The O2- degree production was significantly higher in the group of septic patients than in the others, regardless of the polymorphonuclear leukocyte count. Vitamin E and simvastatin induced ex vivo an inhibition of O2- degree production of 20% and 40% respectively. In vitro, simvastatin inhibited phorbol myristate acetate-induced- O2- degree production by monocytes through NADPH oxidase inactivation. We conclude that sepsis is associated with a significant decrease in vitamin E and an overproduction of O2- degree. Vitamin E and simvastatin lessen this phenomenon through NADPH oxidase inactivation.

APACHE↗

PubMed2004

On-line hemodiafiltration as routine treatment of end-stage renal failure: why pre- or mixed dilution mode is necessary in on-line hemodiafiltration today?

Hemodiafiltration (HDF) is a well-recognized treatment modality that offers a way of optimizing renal replacement therapy efficacy of end-stage renal disease (ESRD) patients. On-line production of substitution fluid by the 'cold sterilization' process (ultrafiltration) gives access to an unlimited amount of sterile and non-pyrogenic IV grade solution. This advantageous low-cost solution may therefore be employed to develop various forms of high-flux HDF modalities (ol-HDF). High-flux post-dilutional HDF (post-HDF) has mainly been used in clinical practice since it offers the most efficient and best compromise between diffusive and convective clearances. Nowadays, the new targets in anemia correction have created hemorheological conditions that render high filtration rate more difficult to achieve and/or at the expense of higher transmembrane pressure. To overcome this new challenging condition and keeping the same concept, it has been proposed to develop alternative modalities with various sites of fluid substitution (predilution, mixed pre-post with various percentages) in HDF. In this presentation we discuss the benefits of using pre-HDF and show how to match performances with post-HDF. Potential advantages of new ol-HDF options (pre-, mixed and mid-dilution) that are advocated have to be demonstrated in clinical trials. On-line HDF is a multipurpose treatment method that is employed to improve care and outcomes of ESRD patients. Due to its versatility, ol-HDF should be considered as a technical platform permitting to personalize and tailor treatment to patients' needs. The mode of substitution (post-, pre-, mixed or mid-dilution) should be established according to hemorheological conditions of the individual patient.

Dialysis Solutions↗

PubMed2003

Vitamin E supplementation increases LDL resistance to ex vivo oxidation in hemodialysis patients.

BACKGROUND: Oxidative stress and alterations in lipid metabolism observed in hemodialysis patients potentiate the low-density lipoprotein (LDL) oxidability, recognized as a key event during early atherogenesis. OBJECTIVE: To explore the effects of an oral vitamin E supplementation on oxidative stress markers and LDL oxidability in hemodialysis patients. METHODS: Fourteen hemodialysis patients and six healthy volunteers were given oral vitamin E (500 mg/day) for six months. Oxidative stress was assessed using: plasma and lipoprotein vitamin E levels [high-performance liquid chromatography (HPLC) procedure]; thiobarbituric acid reactive substances (TBARS, Yaggi method); and copper-induced LDL oxidation. All parameters were evaluated before initiation of vitamin E supplementation, and at three and six months thereafter. RESULTS: At baseline, a significantly higher TBARS concentration and a higher LDL oxidability were observed in hemodialysis patients when compared to controls. After six months of vitamin E supplementation, TBARS and LDL oxidability were normalized in hemodialysis patients. CONCLUSION: Our data confirm that hemodialysis patients are exposed to oxidative stress and increased susceptibility to ex vivo LDL oxidation. Since oral vitamin E supplementation prevents oxidative stress and significantly increases LDL resistance to ex vivo oxidation, supplementation by natural antioxidants such as vitamin E may be beneficial in hemodialysis patients.

Analysis of Variance↗

PubMed2002

Free knot splines for biochemical data.

The use of spline functions in the analysis of empirical two-dimensional (2-D) data (y(i), x(i)) is described. Spline functions are excellent empirical functions, which can be used with advantage instead of other ones, such as polynomials or exponentials. The knot location seen as variable value corresponds to classical parameter used to describe oxidation curves. An application on characterization of LDL oxidability shows free knot splines in a regression context.

Linear Models↗

PubMed2002

Oxidative stress in hemodialysis patients: is NADPH oxidase complex the culprit?

Oxidative stress results from an imbalance between oxidant production, including reactive oxygen species (ROS), reactive nitrogen species (RNS), chlorinated compounds, and antioxidant defense mechanisms. Most reports prove that oxidative stress is present in ESRD patients. Several studies tend to accreditate the hypothesis by which oxidative stress is a strong co-factor for the development of complications related to long-term HD such as atherosclerosis, amyloidosis, malnutrition, anemia, and infection. In order to evaluate the rationale for curative action against oxidative damage in chronic renal failure patients, we reviewed the putative factors involved in this process. Antioxidant systems are severely impaired in uremic patients and gradually altered with the degree of renal failure. Moreover, the inflammatory state caused by the hemoincompatibility of the dialysis system plays a critical role in the activation of NADPH oxidase, aggravating the pro-oxidant status of uremic patients. Prevention of ROS overproduction by improvement of dialysis biocompatibility, an important component of adequate dialysis, might be completed by antioxidant supplementation.

Humans↗

PubMed2002

Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients.

BACKGROUND: Enhanced oxidative stress in haemodialysis (HD) patients may be considered as a risk factor for accelerated atherosclerosis. Reduced antioxidant defences include impairment in enzyme activities and decreased plasma levels of hydrophilic vitamin C (vit C), and cellular levels of lipophilic vitamin E (vit E). METHODS: We investigated plasma levels of vit C in 19 patients undergoing regular haemodiafiltration (HDF) (mean age 62+/-7 years) and in 1846 healthy elderly subjects (HS) (mean age 69+/-5 years). The contribution of convection and diffusion was determined using paired filtration dialysis (PFD), a modified HDF technique which physically separates convective from diffusive fluxes. Blood samples were collected before and after the HDF session; in addition at 60 min of HDF, samples were drawn from arterial lines (AL) and venous lines (VL), dialysate (D) and ultrafiltrate (UF). Blood levels of total vit C were determined using an HPLC fluorescence method. Markers of oxidative stress were also assessed in both populations as follows: levels of malondialdehyde (MDA) were determined by fluorometric assay, measurements of advanced oxidation protein products (AOPP) and glutathione peroxidase (GSH-Px) activity were performed by spectrophotometric assay, and plasma vit E content was obtained by an HPLC procedure. RESULTS: A significant reduction in plasma vit C level was observed in HDF patients when compared with HS (1.6+/-1.4 microg/ml in HDF vs 6.6+/-3.7 microg/ml in HS; P<0.01). The HDF session was associated with a dramatic reduction in vit C levels (1.87+/-1.57 microg/ml before HDF and 0.98+/-0.68 microg/ml after HDF); at 60 min of HDF, concentrations were as follows: AL=1.35+/-1.27 microg/ml; VL=0.37+/-0.31 microg/ml, D=0.40+/-0.34 microg/ml, UF=1.24+/-1.18 microg/ml; corresponding to a diffusive flux of 271 microg/min and a convective flux of 126 microg/min. Total loss of vit C could be assessed at 66 mg/session (8--230 mg/session). According to this loss of vit C, presence of an oxidative stress was demonstrated in HD population as shown by a significant increase in MDA (1.66+/-0.27 microM in HD vs 0.89+/-0.25 microM in HS; P<0.01) and AOPP (77.5+/-29.3 microM in HD vs 23.5+/-13.2 microM in HS; P<0.01) levels, and a decrease in GSH-Px activity (259.2+/-106.3 U/l in HD vs 661.2+/-92.2 U/l in HS; P<0.01). No change in plasma vit E between both populations (30.7+/-9.1 microM in HD vs 35.3+/-7.34 microM in HS) was observed. CONCLUSIONS: These results suggest that HDF with highly permeable membranes is associated with a significant loss of vit C. Diffusive transport is responsible for two-thirds whereas convective phenomenon accounts for only one-third of this loss.

Adult↗

PubMed2002

Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are able to reduce superoxide anion production by NADPH oxidase in THP-1-derived monocytes.

Reactive oxygen species formation by phagocytes and subsequent modifications of vascular wall are involved in the early step of human atherogenesis. This study looked for the effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors on NADPH oxidase-dependent superoxide anion production in THP-1 cells, a monocyte-derived cell line, and on the translocation of p21 Rac 2 and p67. A 30-min incubation with simvastatin (50 micro M ) inhibited phorbol 12-myristate 13-acetate-induced superoxide anion production by monocytes (32%) and a maximum inhibition was obtained at 3 h of incubation (69.5%). In addition, after 3 h of incubation a dose-dependent inhibition was obtained in the range 10-50 micro M of simvastatin with a median inhibitory concentration of 36 +/- 2.3 micro M Mevalonic acid (100 and 300 micro M ) and geranylgeraniol (100 micro M ) totally prevented the simvastatin-induced inhibitory effect of superoxide production by monocytes whereas farnesyl PP (100 micro M ) partially prevented (50%) this effect. In addition, simvastatin inhibited the translocation of p21 rac 2 and p67, suggesting that geranylgeranylation is required for NADPH oxidase activation. In another set of experiments, the rank order of potency of different statins on NADPH oxidase was determined (pravastatin < cerivastatin < lovastatin < fluvastatin < simvastatin). In conclusion, inhibition of superoxide formation by HMG CoA reductase inhibitors is highly suitable to prevent or limit the oxidative stress involved in the atherosclerosis process.

Dose-Response Relationship, Drug↗