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Research Interests: Immunology, Kidney transplantation, Medicine, Serology, Humans, and 15 moreFemale, Male, Cytomegalovirus, Incidence, CD, Middle Aged, Adult, Retrospective Studies, Cytomegalovirus Infections, Graft Rejection, Chronic Kidney Failure, Postoperative Complications, Human Cytomegalovirus, Human leukocyte antigen, and Medical and Health Sciences
Research Interests: Kidney transplantation, Medicine, Logistic Regression, Humans, Female, and 15 moreMale, Regression Analysis, Data Collection, Cyclosporine, Renal Function, Cadaver, Kidney Transplant, Adult, Analysis of Variance, MULTINATIONAL CORPORATION, Observational Study, Delayed graft function, Glomerular Filtration Rate, Immunosuppressive Agents, and Medical and Health Sciences
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Eculizumab In Prevention Of Acute Antibody-Mediated Rejection In Sensitized Deceased-Donor Kidney Transplant Recipients : 1-Year Outcomes
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Research Interests: Urology, Kidney transplantation, Medicine, Prospective studies, Humans, and 15 moreFemale, Male, Cyclosporine, Renal Function, Clinical Sciences, Middle Aged, Adult, Prognosis, Proteinuria, Regimen, Sirolimus, Vascular Endothelial Growth Factor, Glomerular Filtration Rate, Immunosuppressive Agents, and Kidney glomerulus
Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in... more
Whether or not a cyclosporine A (CsA)-free immunosuppressant regimen based on sirolimus (SRL) prevents aortic stiffening and improves central hemodynamics in renal recipients remains unknown. Forty-four patients (48 ± 2 years) enrolled in the CONCEPT trial were randomized at week 12 (W12) to continue CsA or switch to SRL, both associated with mycophenolate mofetil. Carotid systolic blood pressure (cSBP), pulse pressure (cPP), central pressure wave reflection (augmentation index, AIx) and carotid-to-femoral pulse-wave velocity (PWV: aortic stiffness) were blindly assessed at W12, W26 and W52 together with plasma endothelin-1 (ET-1), thiobarbituric acid-reactive substances (TBARS) and superoxide dismutase (SOD) and catalase erythrocyte activities. At W12, there was no difference between groups. At follow-up, PWV, cSBP, cPP and AIx were lower in the SRL group. The difference in PWV remained significant after adjustment for blood pressure and eGFR. In parallel, ET-1 decreased in the SRL group, while TBARS, SOD and catalase erythrocyte activities increased in both groups but to a lesser extent in the SRL group. Our results demonstrate that a CsA-free regimen based on SRL reduces aortic stiffness, plasma endothelin-1 and oxidative stress in renal recipients suggesting a protective effect on the arterial wall that may be translated into cardiovascular risk reduction.
Research Interests: Urology, Kidney transplantation, Medicine, Humans, Internal Medicine, and 15 moreBlood Pressure, Female, Male, Cyclosporine, Arterial stiffness, Aged, Middle Aged, Adult, Endothelin-1, Aorta, Sirolimus, Pulse Wave Velocity, Immunosuppressive Agents, Mycophenolic Acid, and Medical and Health Sciences
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RESUME La place de la France dans la realisation des essais cliniques a promotion industrielle recule depuis 10 ans. Les raisons en sont multiples : 1/ une diminution de l’offre therapeutique francaise liee a un recul de l’industrie... more
RESUME La place de la France dans la realisation des essais cliniques a promotion industrielle recule depuis 10 ans. Les raisons en sont multiples : 1/ une diminution de l’offre therapeutique francaise liee a un recul de l’industrie pharmaceutique francaise qui n ‘a pas pris a temps le virage des biotechnologies, a la difficulte des Biotechs a atteindre une taille critique et des Medtechs a creer des leaders de taille mondiale. 2/ des lourdeurs administratives entrainant un retard des reponses de l’ANSM et des CPP aux procedures d’essais cliniques. 3/ une capacite d’inclusion insuffisante dans les delais impartis. 4 /une demotivation des investigateurs. A l’issue de ses auditions, le groupe de travail de l’Academie nationale de medecine formule des pistes de reflexion et une serie de propositions pour permettre a la France de retrouver son attractivite dans un domaine capital de l’innovation medicale pour le bien des patients.
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ObjectivesHigh rates of clinical acute rejection after kidney transplantation have been reported in people living with HIV (PLHIV), probably as a consequence of drug interactions. We therefore investigated the incidence of acute rejection... more
ObjectivesHigh rates of clinical acute rejection after kidney transplantation have been reported in people living with HIV (PLHIV), probably as a consequence of drug interactions. We therefore investigated the incidence of acute rejection within 6 months of transplantation in HIV‐infected recipients treated with a protease‐inhibitor‐free raltegravir‐based regimen.MethodsThe Agence Nationale de Recherche sur le Sida et les Hépatites Virales (ANRS) 153 TREVE (NCT01453192) study was a prospective multicentre single‐arm trial in adult PLHIV awaiting kidney transplantation, with viral load < 50 HIV‐1 RNA copies/mL, CD4 T‐cell count > 200 cells/μL, and HIV‐1 strains sensitive to raltegravir, aiming to demonstrate 6‐month clinical acute rejection rates < 30%. Time to transplantation was compared with that for uninfected subjects matched for age, sex and registration date.ResultsIn total, 61 participants were enrolled in the study, and 26 underwent kidney transplantation. Two parti...
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Remarkable progress in organ transplantation has led to a dramatic rise in the demand for organs both in adults and children. All pediatric intensive care units (PICUs) are involved in harvesting organs, nevertheless, organs are collected... more
Remarkable progress in organ transplantation has led to a dramatic rise in the demand for organs both in adults and children. All pediatric intensive care units (PICUs) are involved in harvesting organs, nevertheless, organs are collected from a limited number of potential donors. This situation is more a problem of organisation, willingness and ethics than one of techniques.
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We assessed the long-term (M +/- SE: 68 +/- 3 months) arterial pressure and renal function of cadaveric kidney transplant recipients with and without significant (> 70% diameter reduction) transplant renal artery stenosis (TRAS) at... more
We assessed the long-term (M +/- SE: 68 +/- 3 months) arterial pressure and renal function of cadaveric kidney transplant recipients with and without significant (> 70% diameter reduction) transplant renal artery stenosis (TRAS) at angiography. Baseline clinical, immunological and outcome data for 26 patients with TRAS (incidence of TRAS: 6.6%) before and following angioplasty and 72 patients without stenosis at angiography were reviewed and analyzed. The 2 groups were similar with respect to recipient sex ratio and age (45 vs 46), duration of transplantation (7 months), cause of renal failure, donor sex and age, HLA-antigen mismatches and titers of anti-HLA antibodies, CMV infection and anti-CMV antibodies in donors and recipients. The technical success of angioplasty was 92.3%. Restenosis was documented in 6/26 patients (23.1%). Revascularization resulted in a decrease of arterial pressure and number of antihypertensive medications and a lower serum creatinine compared to basel...
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Research Interests: Kidney transplantation, Medicine, Biopsy, Prospective studies, Humans, and 15 moreKidney, Female, Feasibility Studies, Male, Cyclosporine, Risk factors, Middle Aged, Adult, Risk Factors, Graft Rejection, Regimen, Immunosuppressive Agents, discontinuation, Adrenal cortex hormones, and Medical and Health Sciences
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Polymorphonuclear neutrophils (PMN) play a key role in innate immunity. Their activation and survival are tightly regulated by microbial products via pattern recognition receptors such as TLRs, which mediate recruitment of the... more
Polymorphonuclear neutrophils (PMN) play a key role in innate immunity. Their activation and survival are tightly regulated by microbial products via pattern recognition receptors such as TLRs, which mediate recruitment of the IL-1R-associated kinase (IRAK) complex. We describe a new inherited IRAK-4 deficiency in a child with recurrent pyogenic bacterial infections. Analysis of the IRAK4 gene showed compound heterozygosity with two mutations: a missense mutation in the death domain of the protein (pArg12Cys) associated in cis-with a predicted benign variant (pArg391His); and a splice site mutation in intron 7 that led to the skipping of exon 7. A nontruncated IRAK-4 protein was detected by Western blotting. The patient’s functional deficiency of IRAK-4 protein was confirmed by the absence of IRAK-1 phosphorylation after stimulation with all TLR agonists tested. The patient’s PMNs showed strongly impaired responses (L-selectin and CD11b expression, oxidative burst, cytokine producti...
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Summary Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid (MPA) and the area under the curve (AUC) in... more
Summary Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) treatment strategy is based on immunosuppressive agents. Little information is available concerning mycophenolic acid (MPA) and the area under the curve (AUC) in patients treated for AAV. We evaluated the variations in pharmacokinetics for MPA in patients with AAV and the relationship between MPA–AUC and markers of the disease. MPA blood concentrations were measured through the enzyme-multiplied immunotechnique (C0, C30, C1, C2, C3, C4, C6 and C9) to determine the AUC. Eighteen patients were included in the study. The median (range) MPA AUC0–12 was 50·55 (30·9–105·4) mg/h/l. The highest coefficient of determination between MPA AUC and single concentrations was observed with C3 (P < 0·0001) and C2 (P < 0·0001) and with C4 (P < 0·0005) or C0 (P < 0·001). Using linear regression, the best estimation of MPA AUC was provided by a model including C30, C2 and C4: AUC = 8·5 + 0·77 C30 + 4·0 C2 + 1·7 C4 (P &...
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Lymphocyte adhesion to allogeneic endothelium is a critical step in graft rejection. To further characterize the expression and the regulation of adhesion molecules involved in this process, we stimulated endothelial cells with... more
Lymphocyte adhesion to allogeneic endothelium is a critical step in graft rejection. To further characterize the expression and the regulation of adhesion molecules involved in this process, we stimulated endothelial cells with Interleukin 4 or tumor necrosis factor alpha (TNF alpha) and blocked lymphocyte adhesion to stimulated-endothelial cells with monoclonal antibodies. We demonstrated that lymphocytes bound endothelial cells by at least four adhesion pathways: a) a LFA 1/ICAM 1 dependent pathway on TNF alpha-stimulated endothelial cells, b) a LFA 1 dependent/ICAM 1 independent pathway on unstimulated or IL 4-stimulated endothelial cells, c) a VLA 4/VCAM 1 dependent pathway on unstimulated and stimulated-endothelial cells, d) a CD 2 dependent/LFA 3 independent pathway on IL 4 and TNF alpha-stimulated endothelial cells.
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Research Interests: Economics, Kidney transplantation, Comparative Study, Medicine, Prevention, and 15 moreApplied Economics, Clinical Practice, Humans, Cytomegalovirus, Cost effectiveness, Kidney Transplant, Immunocompromised host, Cost Benefit Analysis, Intensive Care Medicine, Management Strategy, Cytomegalovirus Infections, Decision Models, Antiviral Agents, Acyclovir, and High risk
Research Interests: Endocrinology, Chemistry, Biology, Medicine, Lipids, and 15 morePlatelet, Internal Medicine, Platelet aggregation, Fatty acids, Cholesterol, Animals, Eicosanoids, Hypercholesterolemia, Lipid metabolism, Arachidonic Acid, Eicosapentaenoic Acid, Docosahexaenoic Acid, Biochemistry and cell biology, epoprostenol, and Medical and Health Sciences
Research Interests: Epidemiology, Gastroenterology, Incidence Geometry, Kidney transplantation, Adolescent, and 15 moreMedicine, France, Lymphoma, Humans, Internal Medicine, Female, Male, American, Incidence, Middle Aged, Adult, Graft Rejection, Cumulative Incidence, Lymphoproliferative disorders, and Medical and Health Sciences
The IMPACT study was a meticulously designed doubleblinded study, which has been scrutinized and considered robust enough in design, endpoints and outcome, by US and EU health authorities, so as to lead to global label changes in... more
The IMPACT study was a meticulously designed doubleblinded study, which has been scrutinized and considered robust enough in design, endpoints and outcome, by US and EU health authorities, so as to lead to global label changes in prescribing valganciclovir for kidney transplant patients. Kalil et al. state a major weakness of the IMPACT study was inadequate blinding. Active drug and placebo were indistinguishable and fully matched in terms of shape, size, color and labeling. All study investigators, site staff and sponsor, were fully blinded to the treatment allocation until after the analysis of the primary endpoint. Therefore, any conclusions regarding the lack of valid blinding are not scientifically sound. Withdrawal from treatment between groups was indeed different, however the reason for withdrawal was not due to compliance or unblinding as suggested, but due to the development of cytomegalovirus (CMV) disease after the first 100 days. Obviously patients who are being treated for CMV disease can’t continue to get blinded study drug. The suggestion to separately analyze CMV disease in patients who completed 200 days of drug simply does not make sense. Furthermore, a compliance issue did not occur. Compliance was closely monitored, with drug dispense and return logs being performed at each study visit and was comparable between arms. Similarly, the author’s conclusion that patients in the 100day group had more frequent dose adjustments is incorrect; the results show that each group was similar for renal function over time. Dose adjustments were carried out alike for all patients regardless of group, according to renal function.