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Biomedical subjects

François Madore

Publications and source records attributed to François Madore.

14 recordsLinked to original sources
PubMed2006

Uraemic plasma decreases the expression of ABCA1, ABCG1 and cell-cycle genes in human coronary arterial endothelial cells.

BACKGROUND: Uraemia is associated with endothelial dysfunction, but the effect of uraemic plasma on the gene expression pattern of human coronary arterial endothelial cells (HCAEC) has never been defined. METHODS: HCAECs were exposed for 48 h to a culture medium supplemented with 20% uraemic vs normal plasma. We extracted mRNA and hybridized it onto Affymetrix HG-U133 Plus2 microarrays. We validated our findings for five genes of interest by real-time PCR and performed evaluations of cell proliferation and apoptosis in HCAECs exposed to uraemic vs normal plasma. RESULTS: Six genes involved in the regulation of cell-cycle progression (CDK-1, topoisomerase II, PDZ-binding kinase, CDCA1, protein SDP35, E2F transcription factor 8) and two genes of the cholesterol efflux system (ABCA1 and ABCG1) were down-regulated in HCAECs exposed to uraemic plasma (>1.75-fold change vs normal). Real-time PCR confirmed the down-regulation observed in the microarray experiment. Cell proliferation was significantly decreased in HCAECs exposed to uraemic vs normal plasma for 48 h (86 vs 95% of serum-starved control, P = 0.006). Exposure to uraemic plasma for 48 h was associated with increased apoptosis of HCAEC as compared with normal plasma (7.7 vs 2.8%, P < 0.001), a phenomenon that was further enhanced when oxidized LDLs (150 microg protein/ml) were added to the medium containing uraemic plasma (16.9 vs 7.7%, P < 0.001). CONCLUSIONS: The down-regulation of genes involved in cell-cycle progression and cholesterol efflux from HCAECs exposed to uraemic conditions could contribute to enhancing endothelial dysfunction and atherosclerosis in patients with chronic renal failure.

ATP Binding Cassette Transporter 1↗
PubMed2006

Prescription patterns of pharmacological agents for left ventricular systolic dysfunction among hemodialysis patients.

BACKGROUND: Recommendations for the management of left ventricular (LV) systolic dysfunction in the general population and patients with end-stage renal disease (ESRD) include the use of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers. Limited data from the literature suggest that these pharmacological agents may be underused in patients with ESRD. The goal of this study is to describe the use of these medications and investigate barriers to their use in dialysis patients. METHODS: We prospectively studied 420 hemodialysis patients. Diagnosis of systolic dysfunction was based on echocardiogram results. Use of cardiac medication was recorded for all patients with systolic dysfunction, and a questionnaire was administered to nephrologists to determine the basis for decisions concerning ACE-inhibitors and beta-blockers use/nonuse. RESULTS: Forty-seven patients (11%) were found to have an LV ejection fraction of 40% or less. Of those, 72% were administered a beta-blocker and 36% were administered an ACE inhibitor. Only 12 patients (25.5%) were administered a combination of beta-blocker and ACE inhibitor. Reasons indicated by nephrologists for not prescribing these medications were "concern about adverse reactions (eg, hypotension, hyperkalemia)" in 88% of cases, "adequate control of symptoms with ultrafiltration" in 38%, "unproven benefit" in 25%, and "unfavorable risk-benefit ratio" in 17%. Medication costs and concern about patient compliance were not identified as significant concerns by physicians. CONCLUSION: Only 25.5% of patients with ESRD with LV systolic dysfunction receive appropriate treatment. Concern regarding adverse reactions was the most frequent reason indicated by nephrologists for not prescribing ACE inhibitors and beta-blockers.

Adrenergic beta-Antagonists↗
PubMed2004

[Vascular risk factors and renal failure].

Patients with chronic kidney disease (CKD) have a substantially increased risk of cardiovascular disease (CVD) compared with the general population. The high prevalence of established traditional risk factors for atherosclerosis (diabetes, hypertension, dyslipidemia) in these patients undoubtedly contributes to the accelerated rate of vascular disease. In addition, several hypotheses have emerged to explain the high prevalence of CVD in patients with chronic renal failure. Growing evidence has been gathered over the last 15 years regarding the role of uremia-related risk factors such as inflammation and oxidant stress in the pathogenesis of atherosclerosis in subjects with renal failure. This paper will review current knowledge regarding the potential role of these non-traditional or uremia-related risk factors for atherosclerosis with special emphasis on prevalence, cardiac risk, and management in patients with CKD.

Cardiovascular Diseases↗
PubMed2004

Increased risk of thrombotic microangiopathy in patients receiving a cyclosporin-sirolimus combination.

A single-center cohort study of kidney and kidney-pancreas recipients was conducted to evaluate the association between new immunosuppressive regimens and risk of thrombotic microangiopathy (TMA). From January 1st,1996 to December 31, 2002, 368 patients received a kidney or kidney-pancreas transplant at our center. Four immunosuppressive regimens were evaluated as potential risk factors of TMA: cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA + SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus (FK + SRL). Thirteen patients developed biopsy-proven TMA in the absence of vascular rejection. The incidence of TMA was significantly different in the four immunosuppressive regimens studied (p < 0.001). The incidence of TMA was highest in the CsA + SRL group (20.7%). The relative risk of TMA was 16.1 [95% confidence interval (CI): 4.3-60.8] for patients in the CsA + SRL group as compared with those in the FK + MMF group. We also investigated in vitro the pathophysiological basis of this association. The CsA-SRL combination was found to be the only regimen that concomitantly displayed pro-necrotic and anti-angiogenic activities on arterial endothelial cells. We propose that this combination concurs to development of TMA through dual activities on endothelial cell death and repair.

Adult↗
PubMed2003

A novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration.

OBJECTIVE: Validation of a novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration (CVVHDF). DESIGN AND SETTING: Prospective cohort trial in medicosurgical intensive care units of two university-affiliated teaching institutions. PATIENTS: Participants were patients at high risk for bleeding, with renal failure requiring CVVHDF without heparin. Fourteen patients completed the study. INTERVENTION: A convection-based citrate anticoagulation CVVHDF regimen using an isotonic replacement fluid containing citrate administered in predilution. A neutralizing solution of calcium chloride and magnesium sulfate was infused at the end of the circuit. Blood flow rate was set and kept at 125 ml/min, and the flow rate of the replacement fluid was initiated at 1250 ml/h and adjusted thereafter according to the monitoring of blood activated coagulation time (ACT), with a target between 180 to 220 s. MEASUREMENTS AND RESULTS: The average filter time-life was 44 h. Thrombosis of the proximal portion of the circuit (which was not anticoagulated) was the main reason for technique failure. A mean urea clearance of 21 ml/min was obtained. Electrolytes and acid-base balance were both well maintained. Six percent (16/287) of Ca(i) readings less than 0.3 mmol/l were associated with very high ACT levels (>300 s). CONCLUSIONS: This regimen is shown to be safe, efficacious, and convenient. Citrate anticoagulation should be monitored using postfilter ACT and/or ionized calcium with respective targets of 200-250 s or 0.3-0.4 mmol/l.

Anticoagulants↗
PubMed2003

Soluble Fas: a novel predictor of atherosclerosis in dialysis patients.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death in patients with end-stage renal disease (ESRD). Disregulation of apoptosis within the vessel wall and upregulation of the Fas/Fas-ligand (Fas-L) system contribute to the development of atherosclerosis. Cross-sectional studies have suggested that elevated plasma levels of the soluble form of Fas (sFas) are associated with CVD. However, the role of sFas and sFas-L in predicting future cardiovascular events has yet to be defined. METHODS: We evaluated the role of plasma sFas and sFas-L levels as predictors of CVD in a prospective cohort of 107 chronic hemodialysis patients. RESULTS: During the study period (27 months), 53 patients (49.5%) presented with at least one cardiovascular end point. On univariate analysis, baseline sFas levels were significantly associated with the occurrence of cardiovascular end points, whereas sFas-L levels were not. Using Cox proportional hazards, increased sFas levels were associated with a significantly greater risk for cardiovascular end points (P = 0.03). This effect was independent of baseline CVD history, classic risk factors for atherosclerosis (diabetes, hypercholesterolemia, hypertension, and smoking), and markers of inflammation (C-reactive protein [CRP], soluble intercellular adhesion molecule-1). Increased CRP levels also were associated with cardiovascular end points (P = 0.04). In addition, increased cardiovascular mortality was found in patients in the highest sFas tertile compared with those in the lowest tertile (27.8% versus 8.6%; P = 0.04). CONCLUSION: Increased plasma sFas levels are predictive of future CVD. These results suggest that sFas is a novel and independent predictor of active atherosclerotic disease in patients with ESRD.

Aged↗
PubMed2002

Enhanced development of caspase-independent cortical cell death during cold storage in kidneys of non-heart-beating donors.

BACKGROUND: Understanding the mechanisms of injury associated with cardiac arrest is essential for defining strategies aimed at improving preservation and function of kidneys harvested in non-heart-beating (NHB) donors. METHODS: We standardized a model of NHB donors in rats and studied the kinetics and types (apoptosis vs. necrosis) of renal cell death developing during cold storage. Using quantitative polymerase chain reaction, immunoblotting, and caspase inhibition, we also studied the molecular pathways regulating renal cell death in this model. RESULTS: The kinetics and extent of cell death developing in cortical tubules during cold storage were found to be increased in non-heart-beating (NHB) kidneys. Apoptosis of cortical tubules predominated in NHB kidneys exposed to 10 hr of cold storage, whereas necrosis increased after longer periods of cold ischemia. Shortly after cardiac arrest, a rapid up-regulation of Bax and Hsp 70 was found at the protein level in NHB kidneys. After 24 hr of cold storage, induction of Bax was maintained, whereas protein levels of Hsp70 returned to levels comparable to heart-beating (HB) controls. Also, mRNA levels of Bax were found to increase during cold storage in NHB kidneys. Cortical cell death was found to be largely caspase-independent but responsive to hydroxyl-radical scavenging with dimethyl sulfoxide (DMSO). CONCLUSIONS: Cardiac arrest promotes activation of death-inducing molecules such as Bax and is associated with increased development of caspase-independent renal cell death during cold storage. Developing strategies, such as free radical scavenging, aimed at inhibiting cell death during cold storage, could prove useful for improving preservation of NHB kidneys.

Amino Acid Chloromethyl Ketones↗
PubMed2002

Plasmapheresis. Technical aspects and indications.

In summary, use of plasmapheresis has changed in recent years given advances in medical technology that have allowed a wider clinical application in the critical care setting. Membrane filtration technology has provided an alternative to centrifugation that can be easily applied in intensive care units. Use of plasmapheresis has also changed in recent years reflecting the availability of evidence largely obtained from controlled prospective studies. However, the clinical efficacy of plasmapheresis for many acute renal conditions is still controversial. Plasmapheresis appears to be a useful adjunct to conventional therapy in the treatment of anti-GBM nephritis, severe dialysis-dependent forms of pauciimmune RPGN, cryoglobulinemia, and HUS-TTP. Reported data also suggest a possible benefit of plasmapheresis in patients with myeloma cast nephropathy, sepsis, and poisoning/overdose, but the case for plasmapheresis in these disorders is largely unproven and the reported evidence insufficient to recommend its use outside research settings. In contrast, data from controlled trials do not support a role for plasmapheresis in immune complex-mediated RPGN, such as lupus nephritis, and acute allograft rejection. The more widespread application of prospective, randomized, controlled clinical trials should help to better define the value of plasmapheresis for treatment of acute renal diseases.

Glomerulonephritis↗
PubMed2002

Soluble Fas is a marker of peripheral arterial occlusive disease in haemodialysis patients.

BACKGROUND: Peripheral arterial occlusive disease (PAOD) including lower-extremity and cerebrovascular atherosclerosis is a leading cause of morbidity in haemodialysis patients. Recent evidence suggests that the expression of Fas, a molecule implicated in the initiation of apoptosis in various cell types, is increased at sites of atherosclerotic plaques. However, the significance of plasma levels of the soluble form of Fas (sFas) as a marker of peripheral arterial disease has yet to be defined. METHODS: The present report is based on a cross-sectional analysis of baseline data from an ongoing prospective study designed to evaluate the role of sFas as marker of PAOD in end-stage renal disease (ESRD). We evaluated the association between sFas levels and evidence of PAOD in a cohort of 107 chronic haemodialysis patients. RESULTS: Compared with subjects without evidence of disease (n=56), subjects with PAOD (n=51) had significantly higher plasma levels of sFas (30.0+/-8.9 vs 26.4+/-9.5 ng/ml; P=0.04). Using multiple regression, sFas was found to be associated with PAOD independently of classical risk factors for atherosclerosis (hypercholesterolaemia, diabetes, hypertension, and smoking), markers of inflammation (e.g. C-reactive protein, intercellular cell adhesion molecule type 1), and other risk factors (e.g. age, gender). An increase of one quintile in the plasma concentration of sFas was associated with an odds ratio of PAOD of 1.69 (95% CI: 1.09--2.63, P=0.01). In addition, models that incorporated sFas were significantly better at predicting PAOD than models limited to classical risk factors for atherosclerosis, alone or in combination with CRP levels (P=0.01). CONCLUSIONS: Increased plasma levels of sFas are associated with established PAOD. These results suggest that sFas may represent a novel and independent marker of atherosclerosis.

Aged↗
PubMedDate not supplied

Uremia-related metabolic cardiac risk factors in chronic kidney disease.

Growing evidence has been gathered over the last 15 years regarding the role of nontraditional or uremia-related risk factors in the pathogenesis of atherosclerosis in subjects with renal failure. Among those factors, dyslipidemia, inflammation, hyperhomocysteinemia, and oxidant stress have been extensively studied. However, the clinical significance of many of these factors remains controversial in light of reported studies. In this article, the existing evidence regarding the role of uremia-related risk factors in the pathogenesis of atherosclerosis is reviewed, with special emphasis on prevalence, cardiac risk, and management in patients with chronic kidney disease (CKD). Consensus treatment recommendations are provided for risk factors for which there is evidence to support preventive or therapeutic interventions.

Arteriosclerosis↗
PubMedDate not supplied

Biofeedback regulation of ultrafiltration and dialysate conductivity for the prevention of hypotension during hemodialysis.

Intradialytic hypotension remains a frequent complication of dialysis, occurring in up to 33% of patients. We tested a fully integrated biofeedback system (the Hemocontrol system) that monitors and regulates blood volume contraction during hemodialysis. Seven hypotension prone patients were selected for the study. We conducted a prospective crossover study alternating dialysis sessions using the blood volume regulation system and standard dialysis sessions. Event free sessions were defined as dialysis sessions not requiring any therapeutic intervention for hypotension related signs or symptoms. There was a significant improvement in the number of event free sessions with blood volume regulation compared with standard dialysis (50.8% of sessions vs. 29.2%; p < 0.01). Percentages of event free sessions and mean postdialysis systolic blood pressure improved progressively over the course of the study, indicating improved hemodynamic stability over the study period. Therefore, the use of a biofeedback system to monitor and regulate blood volume during dialysis was helpful in restoring cardiovascular stability in a population of hypotension prone hemodialysis patients. Further studies are needed to confirm these preliminary results and to establish the role of blood volume regulation systems in reducing the incidence of hypotension during hemodialysis.

Adult↗
PubMedDate not supplied

Measurement of blood volume during hemodialysis is a useful tool to achieve safely adequate dry weight by enhanced ultrafiltration.

Chronic fluid overload and hypertension are highly prevalent in the dialysis population. Measurement of blood volume (BV) during hemodialysis (HD) may prove useful to achieve dry weight (DW). Twelve (12) chronic hemodynamically stable dialysis patients were randomly selected to participate in a pilot study. BV changes were measured using an online blood volume monitor (Hemoscan, Gambro AB, Stockholm, Sweden). As part of an initial observation phase, the magnitude of BV variation (deltaBV) in percentage and total UF volume (UF) in liters were recorded for each dialysis session, and the deltaBV/UF ratio was calculated. DW was subsequently reduced by 0.5 kg in all patients and the tolerance of the procedure was assessed. Attempted DW reduction was successful in seven patients, whereas it resulted in hypotension or symptoms in the other five cases. The deltaBV/UF ratio was found to be significantly lower in patients in whom attempted DW reduction was successful (2.47%/L vs. 3.45%/L, P < 0.05). Using receiver operating characteristic (ROC) curve analysis, a deltaBV/UF ratio of less than 2.6%/L offered the best overall prediction of successful DW reduction. These results suggest that measurement of BV changes during HD and calculation of the deltaBV/UF ratio are valuable tools for management of DW in clinically stable patients.

Aged↗
PubMedDate not supplied

Systemic anticoagulation and prevention of hemodialysis catheter malfunction.

Although chronic anticoagulation is commonly prescribed to prevent thrombosis and malfunction of hemodialysis tunneled cuffed catheters (TCC), there are only limited data regarding its efficacy. The aim of this prospective study was to evaluate whether anticoagulation with adjusted-dose warfarin targeting an international normalized ratio (INR) of 1.5-2.0 is associated with improved catheter outcome in long-term patients at high risk of TCC malfunction. Among the 65 patients included in the study, 35 were considered at high risk (i.e., patients with a history of previous TCC thrombosis requiring catheter replacement and/or with TCC malfunction occurring within 2 weeks after catheter insertion in the absence of mechanical problems) and were prescribed warfarin, whereas 30 low-risk patients did not receive anticoagulation. During follow-up, TCC malfunction, defined as the need for inversion of catheter lines and/or recombinant tissue-type plasminogen activator infusion, was observed in 61.5% of patients. Among patients receiving warfarin, 19 (54.3%) achieved adequate anticoagulation (i.e., > 80% of follow-up INR values and INR value at the time of malfunction within target range). Anticoagulation was considered inadequate in 16 patients (45.7%). Malfunction-free catheter survival at 9 months was 47.1% in patients with adequate anticoagulation compared with 8.1% in patients with inadequate anticoagulation (p = 0.01). This difference remained statistically significant after adjustment for aspirin intake. These results suggest that achieving adequate anticoagulation with target INR 1.5-2.0 may prevent TCC malfunction and improve catheter outcome.

Aged↗