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Biomedical subjects

B Canaud

Publications and source records attributed to B Canaud.

At least 19 recordsLinked to original sources

Beta2-microglobulin, a uremic toxin with a double meaning.

beta(2)M is a strong and independent indicator of hemodialysis patient outcomes and an excellent surrogate for middle molecules, and deserves to be routinely monitored and incorporated into dialysis adequacy targets. beta(2)M has a double meaning, reflecting both dialysis efficacy in terms of solute mass transfer and patient bioactivity. The work of Ward et al. in this issue warrants a study to test the hypothesis that long daily hemodiafiltration treatment would be the optimal renal replacement modality to improve dialysis patient outcomes.

Body Fluid Compartments↗

Mortality risk for patients receiving hemodiafiltration versus hemodialysis: European results from the DOPPS.

Hemodiafiltration (HDF) is used sporadically for renal replacement therapy in Europe but not in the US. Characteristics and outcomes were compared for patients receiving HDF versus hemodialysis (HD) in five European countries in the Dialysis Outcomes and Practice Patterns Study. The study followed 2165 patients from 1998 to 2001, stratified into four groups: low- and high-flux HD, and low- and high-efficiency HDF. Patient characteristics including age, sex, 14 comorbid conditions, and time on dialysis were compared between each group using multivariate logistic regression. Cox proportional hazards regression assessed adjusted differences in mortality risk. Prevalence of HDF ranged from 1.8% in Spain to 20.1% in Italy. Compared to low-flux HD, patients receiving low-efficiency HDF had significantly longer average duration of end-stage renal disease (7.0 versus 4.7 years), more history of cancer (15.4 versus 8.7%), and lower phosphorus (5.3 versus 5.6 mg/dl); patients receiving high-efficiency HDF had significantly more lung disease (15.5 versus 10.2%) and received a higher single-pool Kt/V (1.44 versus 1.35). High-efficiency HDF patients had lower crude mortality rates than low-flux HD patients. After adjustment, high-efficiency HDF patients had a significant 35% lower mortality risk than those receiving low-flux HD (relative risk=0.65, P=0.01). These observational results suggest that HDF may improve patient survival independently of its higher dialysis dose. Owing to possible selection bias, the potential benefits of HDF must be tested by controlled clinical trials before recommendations can be made for clinical practice.

Europe↗

Mechanism of in vitro heme-induced LDL oxidation: effects of antioxidants.

BACKGROUND: Heme protein toxicity, owing to generation of reactive oxygen species most likely by direct interaction between heme iron and hydrogen peroxide (H2O2), may be involved in various pathologies, including atherogenesis and pigmentary acute renal failure. The aim of this study was to investigate the mechanism of heme cytotoxicity and the effects of antioxidant therapies in an in vitro model of heme-induced low-density lipoprotein (LDL) oxidation. MATERIALS AND METHODS: Human LDLs were exposed to heme, iron (Fe), protoporphyrin (PPIX) and PPIX-Zinc (Zn) with or without H2O2. Lipid peroxidation was monitored by measurement of conjugated diene formation (at the 234-nm absorbance). The effect of various antioxidants, such as vitamin E and vitamin C, reduced glutathione (GSH), and oxidized glutathione (GSSG), mannitol and desferoxamine (DFO) was further investigated in the established in vitro model of LDL oxidation. RESULTS: Incubation of LDLs in the presence of heme/H2O2 induced lipid peroxidation with the optimal oxidation rate being at 5 microm heme/100 microm H2O2 doses. By contrast, incubation of LDL with H2O2, Fe, Fe/H2O2, PPIX, PPIX/H2O2, heme or PPIX-Zn did not initiate any LDL oxidation. In vitro, the vitamin E load protected native LDLs against heme/H2O2 oxidative modifications. Incubation of LDLs with increasing doses of vitamin C, GSH and DFO conferred a dose-dependent protection, while mannitol and GSSG had no effect. CONCLUSIONS: Initiation and propagation of heme-induced lipid peroxidation is not mediated by a Fenton reaction but depends on specific interactions between heme and H2O2. It may result from the generation of ferryl and perferryl radicals derived from hemic Fe and H2O2 interactions. A protective effect of vitamins E, C, GSH and DFO was demonstrated in this model.

Antioxidants↗

[Is C-reactive protein a marker of inflammation?].

C-reactive protein (CRP) is the prototype of acute-phase protein which is secreted by the liver in response to a variety of inflammatory cytokines. Levels of CRP can increase up to 1000-fold very rapidly after the onset of inflammation and decrease just as rapidly with the resolution of aggression. CRP is a member of the ancient highly conserved pentraxin family of proteins and it is arranged in a cyclic homopentameric structure. The important role of CRP in innate immunity is largely due to its opsonizing abilities, its capability to activate human complement and to bind to immunoglobulin G receptors. CRP can bind phosphocholine largely present in bacterial membranes, cell membrane and lipoproteins, in addition CRP can recognize nuclear constituent in damaged cells. CRP can activate C3 convertase through the classical pathway but not C5 convertase resulting in generation of opsonic complement fragments. Interactions of CRP with Fc receptors lead to the generation of proinflammatory cytokines and reactive oxygen species by monocyte/macrophage while inhibit neutrophiles functions. Recently, CRP was demonstrated to play an active role in atherogenesis and it has been largely proven that a microinflammatory state as defined by a moderate increase in CRP (up to 3 mg/l), is associated with an increased risk for arterial disease. Moreover it has been postulated that CRP may be a useful tool for monitoring drug therapy.

C-Reactive Protein↗

[Vascular access, an underestimated source of inflammation in dialysis patients].

The surveillance of inflammation in dialysis patient, by means of sensitive markers such as CRP, is strongly recommended in a continuous quality improvement treatment approach. Chronic inflammation being deleterious via several pathways including malnutrition, accelerated arteriosclerosis and beta 2M-amyloidosis, microinflammation must diagnosed and corrected as soon as possible in dialysis patients. Vascular access represents an underestimated source of inflammation in hemodialysis patients. In the absence of organic cause of inflammation, the vascular access should be always incriminated and meticulously investigated. Withdrawing the suspected prosthetic or unused material (PTFE or catheter) should be considered as the best way of correcting the inflammation and restoring the recombinant erythropoietin (EPO) activity in the dialysis patient.

Acute Disease↗

Necrotic skin lesions in a dialysis patient: a multifactorial entity.

A female dialysis patient with a consistently high serum calcium phosphate product presented with large necrotic skin lesions with ulcers. The clinical course was highly suggestive of calciphylaxis. Parathyroidectomy was followed by the healing of the lesions. New skin lesions appeared following relapse of hyperparathyroidism. Her clinical records included a long past of hypertension, which was the cause of her renal failure. She had a limited walking range and previously had presented bilateral ulcers of vascular origin. This case presents a type of lesion which bears a serious prognosis in dialysis patients. The clinical context and the presentation of the lesions are compatible with multiple etiology: vascular lesions and calciphylaxis. The documented longitudinal follow-up illustrates the importance of treating the different factors known to participate in the appearance of skin lesions in dialysis patients. Particularly, it stresses the benefit of performing parathyroidectomy, even if the parathyroid hormone level is not in the range normally accepted as requiring surgical removal of parathyroid glands.

Aged↗

[Evolution of medical practice in the care of anemia amd the use of erythropoietin in chronic renal insufficiency hemodialysis in the past six years].

In order to analyze changes in anemia management in the hemodialysis patients, a retrospective survey was performed in 1999 on a representative French sample of patients in hemodialysis treated by EPO since 1992, 1994, 1996, and 1998 respectively. 368 patients were enrolled in 97 centres. At treatment initiation, some patients characteristics have significantly changed: the percentage of type 2 diabetic patients has increased marquedly from 4.5% in 1992 to 22.1% in 1998. The mean time lag between dialysis and EPO treatment initiation has decreased from 3.3 years to 0.9 on the 6-year period. Lastly, the mean hemoglobin level has increased from 73.7 to 78.5 g/l. No significant evolution in the EPO protocol was observed at the initiation as well as in the maintenance phase. An average percentage of 33.7% of patients were treated in i.v. route at initiation with a mean posology of 105.2 IU/kg (respectively 91.4 in s.c.). In the first year of follow-up, the overall mean posology was 84 IU/kg. In conclusion, this survey suggests that anemia management has been optimized over the last 6 years follow-up, including an earlier initiation of EPO treatment and a higher target of hemoglobin while EPO needs were reduced in the same time.

Anemia↗

[Oxidative stress, hemo-incompatibility and complications of long-term dialysis].

Oxidative stress which results from an imbalance between oxidant production and antioxidant defense mechanisms is now a well recognized pathogenesis factor that could be implicated in the hemodialysis (HD)-related pathology. This review focuses on: 1) factors that may be responsible for oxidative stress in HD patients (hemoincompatibility of the dialysis system--hemoreactivity of the membrane and trace amounts of endotoxins- and uremia per se); 2) implication of such phenomenon in long term complications including anemia, amyloidosis, accelerated atherosclerosis and malnutrition and finally and 3) prevention ways consisting in improving the hemocompatibility of the dialysis system and supplementing the deficiency patients with antioxidants.

Anemia↗

[Extrarenal dialysis in end-stage renal disease].

Renal replacement therapy (RRT) has reached its plain maturity. RRT is an unavoidable and banal tool in the armamentorium in the treatment of end stage renal failure (ESRD). It relies on several practical modalities (hemodialysis, peritoneal dialysis and their variants) that permit to satisfy various patient's needs and to ensure the continuity of life support system. Substitution of certain renal endocrine functions (human recombinant erythropoietin, active vitamin D) has brought a new dimension to the treatment of ESRD in improving substantially the quality of life of these patients. Now, if the long-term outcomes confirm the high efficiency of the renal replacement therapies they also draw their limits bounded by the occurrence of a specific pathology of the "long term dialysis" patient. Such dialysis-related pathology is clearly the new challenge for the nephrologist in the XXIst century that should lead to a deep revision of the RRT concept. Optimal treatment of ESRD patients rely clearly on several options that may be used sequentially to solve specific complications and should be part of a complete management program including renal transplantation in patient non contraindicated.

Humans↗

Factors influencing survival in hemodialysis patients aged older than 75 years: 2.5-year outcome study.

The incidence of malnutrition is widely held to be greater in the elderly, but this specific factor has not been extensively studied in elderly dialysis patients. In a 30-month follow-up prospective study, we evaluated the role of nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8 +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in January 1996, predialysis and postdialysis blood samples were collected according to recommended procedures for dialysis quantification. Normalized protein catabolic rate, dialysis adequacy parameters, and estimation of lean body mass (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from predialysis and postdialysis urea and creatinine levels. Overall survival rates were 80% and 65% after 1 and 2 years of follow-up, respectively, and were significantly less in patients with the lower quartile of obs/exp LBM. In univariate analysis using the Cox proportional hazards model, survival was significantly influenced by age, albumin level, prealbumin level, body mass index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable remained significant. Cardiovascular mortality accounted for 52.1% of the patient deaths. We conclude that in elderly HD patients, malnutrition influences overall survival despite adequate dialysis treatment.

Aged↗

Influence of nutritional factors and hemodialysis adequacy on the survival of 1,610 French patients.

Nutritional factors and dialysis adequacy are associated with outcome in hemodialyzed patients, but their relative contribution remains controversial, particularly when dialysis adequacy complies with current recommendations (Kt/V >1.2). Survival, clinical, and nutritional data from a cohort of prevalent 1,610 patients treated by hemodialysis in 20 centers in France have been collected over a 2.5-year period, from January 1996 to July 1998. Data including age, sex, cause of end-stage renal disease (ESRD), clinical outcome, time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were analyzed. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) from creatinine generation were computed from pre- and postdialysis urea and creatinine levels. The characteristics of the patients were as follows: age 59.6 +/- 16.5 years, 58.8% males, 11% of diabetics, time on dialysis 63.2 +/- 64.5 m. Weekly dialysis time was 12.18 +/- 1.78 hrs, Kt/V 1.34 +/- 0.34, nPCR 1.10 +/- 0.35 g/kg body weight/day. Albumin concentration was 39.4 +/- 5.3 g/L, prealbumin was 0.33 +/- 0.09 g/L, BMI was 23.0 +/- 4.5 kg/m(2). Overall survival was 89.7% +/- 0.8% and 78.4% +/- 1.1% after 1 and 2 years. In the Cox proportional hazard model, survival was significantly influenced by age, the presence of diabetes, and by concentrations of albumin and prealbumin, but not by other variables, including Kt/V and urea reduction ratio. These results indicate that nutritional protein concentrations were predictive of dialysis outcome, whereas variables reflecting actual body composition and dialysis dose were not. Furthermore, in this well-dialyzed population, dialysis adequacy had no influence on survival. In conclusion, when adequacy targets are met in hemodialyzed patients, survival is mainly dependent on age and nutritional status. Efforts should be focused on the most efficient ways to maintain nutritional status in these patients.

Adult↗

Cellular interleukin-1 receptor antagonist production in patients receiving on-line haemodiafiltration therapy.

BACKGROUND: Repetitive exposure to cytokine-inducing substances (pyrogens) results in chronic inflammation, which may significantly contribute to some of the long-term complications in dialysis patients. On-line dialysis modalities, such as on-line haemodiafiltration (HDF), raise particular concerns because of the administration of infusate prepared from potentially contaminated dialysis fluid. Hence, great retention capability for pyrogens is of critical importance for the safe performance of on-line systems. METHODS: The microbiological safety of a novel on-line system, ONLINEplus(TM), was assessed in clinical practice in five centres for 3 months. Infusate and dialysis fluid were regularly monitored for microbial counts, endotoxins, and cytokine-inducing activity. Levels of interleukin-1 receptor antagonist (IL-1Ra) were determined in supernatants of whole blood incubated either under pyrogen-free conditions (spontaneous cytokine production) or following low-dose endotoxin exposure (LPS-stimulated cytokine production). RESULTS: We failed to detect microorganisms or endotoxin contamination of infusate during the entire study period. Moreover, neither infusate nor dialysis fluid demonstrated cytokine-inducing activity. Intradialytic IL-1Ra induction was not detected, as there was no difference between pre- and post-session values for both spontaneous and LPS-stimulated IL-1Ra production (115+/-26 vs 119+/-27 and 2445+/-353 vs 2724+/-362 pg/10(6) white blood cells (WBC), respectively). Neither the number of immunocompetent cells nor their capacity to produce IL-1Ra declined during this period, indicating that cells were not significantly stimulated during treatment. Spontaneous and LPS-induced exvivo IL-1Ra generation remained unchanged after 3 months of on-line HDF therapy as compared with the start of the study (71+/-30 pre- vs 48+/-14 post-study, and 2559+/-811 vs 2384+/-744 pg/10(6) WBC, respectively). CONCLUSIONS: The present on-line system performed safely from a microbiological view-point as both the dialysis fluid and infusate were consistently free of microorganisms, endotoxins, and cytokine-inducing substances. As a result, on-line HDF therapy had no effect upon the chronic inflammatory responses in end-stage renal disease patients.

Adult↗