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2. Rapport 21-13. Formation des chirurgiens/des équipes chirurgicales à la chirurgie robot-assistée. État de la situation actuelle. Propositions d’améliorations

Author

Bagot, M., Pion, M., Vuitton, D.A., Bertrand, D., Bonnin, A., Bontoux, D., Boudjema, K., Bringer, J., Caton, J., Charpentier, B., Chays, A., Christmann, D., Couturier, D., Delpech, M., Deugnier, Y., Dubousset, J., Dussaule, J.C., Fabiani, J.N., Gueant, J.L., Hauet, T., Hubert, J., Huriet, C., Lebranchu, Y., Le Gall, J.Y., Legent, F., Levy-Brul, D., Levy, P., Logeais, Y., Loisance, D., Ludes, B., Malafosse, M., Mandarim-De-Lacerda, C., Mantion, G., Marescaux, J., Michot, F., Mornex, R., Ourabah, R., Poitout, D., Queneau, P., Ricco, J.B., Richard, F., de Saint Julien, J., Sassard, J., Stoltz, J.F., Vouhé, P., Tran Ba Huy, P., Delmas, V., and Vouhe, P.

Published
2022
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5. Reduction of Extended-Release Tacrolimus Dose in Low-Immunological-Risk Kidney Transplant Recipients Increases Risk of Rejection and Appearance of Donor-Specific Antibodies: A Randomized Study

Author

Gatault, P., Kamar, N., Büchler, M., Colosio, C., Bertrand, D., Durrbach, A., Albano, L., Rivalan, J., Le Meur, Y., Essig, M., Bouvier, N., Legendre, C., Moulin, B., Heng, A.-E., Weestel, P.-F., Sayegh, J., Charpentier, B., Rostaing, L., Thervet, E., and Lebranchu, Y.

Published
2017
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6. Genome-Wide Association Study of Acute Renal Graft Rejection

Author

Ghisdal, L., Baron, C., Lebranchu, Y., Viklický, O., Konarikova, A., Naesens, M., Kuypers, D., Dinic, M., Alamartine, E., Touchard, G., Antoine, T., Essig, M., Rerolle, J.P., Merville, P., Taupin, J.L., Le Meur, Y., Grall-Jezequel, A., Glowacki, F., Noël, C., Legendre, C., Anglicheau, D., Broeders, N., Coppieters, W., Docampo, E., Georges, M., Ajarchouh, Z., Massart, A., Racapé, J., Abramowicz, D., and Abramowicz, M.

Published
2017
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24. The Spiesser Study: Results at 8 Years.: Abstract# B983

Author

Gatault, P., Snanoudj, R., Toupance, O., Weestel, F., de Ligny, Hurault B., Buchler, M., Rerolle, J., Thierry, A., Moulin, B., Subra, J., Heng, A., Etienne, I., LePogamp, P., Sautenet, B., and Lebranchu, Y.

Published
2014

28. Efficiency of immunoglobulin G replacement therapy in common variable immunodeficiency: correlations with clinical phenotype and polymorphism of the neonatal Fc receptor

Author

Gouilleux-Gruart, V., Chapel, H., Chevret, S., Lucas, M., Malphettes, M., Fieschi, C., Patel, S., Boutboul, D., Marson, M.-N., Gérard, L., Lee, M., Watier, H., Oksenhendler, E., Galicier, L., Fermand, J. P., Viallard, J. F., Jaccard, A., Hoarau, C., Lebranchu, Y., Bérezné, A., Mouthon, L., Karmochkine, M., Georgin-Lavialle, S., Schleinitz, N., Durieu, I., Nove-Josserand, R., Chanet, V., Le-Moing, V., Just, N., Salanoubat, C., Jaussaud, R., Suarez, F., Hermine, O., Solal-Celigny, P., Hachulla, E., Sanhes, L., Gardembas, M., Pellier, I., Tisserant, P., Pavic, M., Bonnotte, B., Haroche, J., Amoura, Z., Alric, L., Thiercelin, M. F., Tetu, L., Adoue, D., Bordigoni, P., Perpoint, T., Sève, P., Rohrlich, P., Pasquali, J. L., Soulas, P., Couderc, L. J., Catherinot, E., Giraud, P., Baruchel, A., Deleveau, I., Chaix, F., Donadieu, J., Tron, F., Larroche, C., Blanc, AP, Masseau, A., Hamidou, M., Kanny, G., Morisset, M., Millot, F., Fain, O., Borie, R., Perlat, A., Martinez, V., Bienvenu, B., Debré, P., Mouillot, G., Théodorou, I., Rabian, C., Carmagnat, M., Vince, N., and Bono, C.

Published
2013
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38. Safety and efficacy of eculizumab for the prevention of antibody-mediated rejection after deceased-donor kidney transplantation in patients with preformed donor-specific antibodies

Author

Glotz, D., Russ, G., Rostaing, L., Legendre, C., Tufveson, G., Chadban, S., Grinyo, J., Mamode, N., Rigotti, P., Couzi, L., Buchler, M., Sandrini, S., Dain, B., Garfield, Malcolm, Ogawa, M., Richard, T., Marks, W. H., Merville, P., Lebranchu, Y., Mjornstedt, L., Hughes, P., Torpey, N., and Kamar, N.

Subjects
Graft Rejection, Male, donors and donation, kidney transplantation/nephrology, 030230 surgery, sensitization, complement biology, clinical research/practice, donors and donation: deceased, immunosuppressant-fusion proteins and monoclonal antibodies, rejection: antibody-mediated (ABMR), 0302 clinical medicine, Isoantibodies, Risk Factors, deceased, Immunology and Allergy, Medicine, Pharmacology (medical), Kidney transplantation, biology, Graft Survival, Eculizumab, Middle Aged, Prognosis, practice, Tissue Donors, Survival Rate, Monoclonal, Female, Patient Safety, rejection, Antibody, medicine.drug, Adult, Adolescent, nephrology, kidney transplantation, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Young Adult, antibody-mediated (ABMR), Humans, In patient, Survival rate, Aged, Transplantation, business.industry, Kirurgi, medicine.disease, Kidney Transplantation, Complement Inactivating Agents, clinical research, Immunology, biology.protein, Kidney Failure, Chronic, Surgery, business, Follow-Up Studies
Abstract

The presence of preformed donor-specific antibodies in transplant recipients increases the risk of acute antibody-mediated rejection (AMR). Results of an open-label single-arm trial to evaluate the safety and efficacy of eculizumab in preventing acute AMR in recipients of deceased-donor kidney transplants with preformed donor-specific antibodies are reported. Participants received eculizumab as follows: 1200 mg immediately before reperfusion; 900 mg on posttransplant days 1, 7, 14, 21, and 28; and 1200 mg at weeks 5, 7, and 9. All patients received thymoglobulin induction therapy and standard maintenance immunosuppression including steroids. The primary end point was treatment failure rate, a composite of biopsy-proved grade II/III AMR (Banff 2007 criteria), graft loss, death, or loss to follow-up, within 9 weeks posttransplant. Eighty patients received transplants (48 women); the median age was 52 years (range 24-70 years). Observed treatment failure rate (8.8%) was significantly lower than expected for standard care (40%; P < .001). By 9 weeks, 3 of 80 patients had experienced AMR, and 4 of 80 had experienced graft loss. At 36 months, graft and patient survival rates were 83.4% and 91.5%, respectively. Eculizumab was well tolerated and no new safety concerns were identified. Eculizumab has the potential to provide prophylaxis against injury caused by acute AMR in such patients (EudraCT 2010-019631-35).

Published
2018

39. Early Conversion From Calcineurin Inhibitor- to Everolimus-Based Therapy Following Kidney Transplantation: Results of the Randomized ELEVATE Trial

Author

de Fijter, J. W., Holdaas, H., Oyen, O., Sanders, J. -S., Sundar, S., Bemelman, F. J., Sommerer, C., Pascual, J., Avihingsanon, Y., Pongskul, C., Oppenheimer, F., Toselli, L., Russ, G., Wang, Z., Lopez, P., Kochuparampil, J., Cruzado, J. M., van der Giet, M., Gaite, L. E., Lopez, V. F., Maldonado, R., Massari, P., Novoa, P., Palti, G., Chadban, S., Kanellis, J., Masterson, R., Oberbauer, R., Saemann, M., Kuypers, D., Lohmus, A., Cassuto, E., Frimat, L., Lebranchu, Y., Le Meur, Y., Rostaing, L., Hauser, A., Muehlfeld, A., Nashan, B., Suwelack, B., Weithofer, P., Witzke, O., Zeier, M., Apostolou, T., Boletis, I., Gourmenos, D., Jasuja, S., Khullar, D., Ravishankar, M. S., Sharma, R. K., Garosi, G., Rigotti, P., Tisone, G., Todeschini, P., Acevedo, R., Rozentais, R., Juarez, F. J., Mier, G. M., Urrea, M., Machado, D., Nolasco, F., Sampaio, S., Dubanova, A., Lucan, M., Kolsanov, A. V., Medvedev, V. L., Moysyuk, Y. G., Nesterenko, V., Perlin, D. V., Ulyankina, I. V., Zagainov, E., Dalmau, A., Hernandez, D., Millan, S., Avhingsanon, Y., Turkmen, A., Tuncer, M., Yildiz, A., DIPARTIMENTO DI MEDICINA SPECIALISTICA, DIAGNOSTICA E SPERIMENTALE, Facolta' di MEDICINA e CHIRURGIA, Kuypers, Dirk, AII - Inflammatory diseases, Nephrology, AII - Amsterdam institute for Infection and Immunity, Groningen Kidney Center (GKC), and Groningen Institute for Organ Transplantation (GIOT)

Subjects
Graft Rejection, Male, HLA ANTIBODIES, immunosuppressant, kidney transplantation/nephrology, ELEVATE study, SIROLIMUS, immunosuppression/immune modulation, 030204 cardiovascular system & hematology, 030230 surgery, Pharmacology, Kidney Function Tests, Kidney Failure, 0302 clinical medicine, Postoperative Complications, cardiovascular disease, Risk Factors, Clinical endpoint, Immunology and Allergy, DONOR-SPECIFIC ANTIBODIES, Pharmacology (medical), Chronic, CARDIAC-HYPERTROPHY, Kidney transplantation, calcineurin inhibitor (CNI), clinical research/practice, clinical trial, kidney (allograft) function/dysfunction, mechanistic target of rapamycin: everolimus, Everolimus, Female, Follow-Up Studies, Glomerular Filtration Rate, Graft Survival, Humans, Immunosuppressive Agents, Kidney Failure, Chronic, Kidney Transplantation, Middle Aged, Prognosis, Tacrolimus, RENAL-TRANSPLANTATION, Kidney transplant, ELEVATE study, Certican, Life Sciences & Biomedicine, medicine.drug, medicine.medical_specialty, Certican, Urology, Renal function, Mycophenolic acid, 03 medical and health sciences, LEFT-VENTRICULAR MASS, PRESSURE-OVERLOAD, medicine, Kidney transplant, Transplantation, Science & Technology, business.industry, medicine.disease, Settore MED/18, Calcineurin, RECIPIENTS, MAMMALIAN TARGET, Sirolimus, CYCLOSPORINE, Surgery, business
Abstract

none 24 si In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n = 359) or remain on standard calcineurin inhibitor (CNI) therapy (n = 356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and steroids. The primary endpoint, change in estimated glomerular filtration rate (eGFR) from randomization to month 12, was similar for everolimus versus CNI: mean (standard error) 0.3(1.5) mL/min/1.732 versus -1.5(1.5) mL/min/1.732 (p = 0.116). Biopsy-proven acute rejection (BPAR) at month 12 was more frequent under everolimus versus CNI overall (9.7% vs. 4.8%, p = 0.014) and versus tacrolimus-treated patients (2.6%, p < 0.001) but similar to cyclosporine-treated patients (8.8%, p = 0.755). Reporting on de novo donor-specific antibodies (DSA) was limited but suggested more frequent anti-HLA Class I DSA under everolimus. Change in left ventricular mass index was similar. Discontinuation due to adverse events was more frequent with everolimus (23.6%) versus CNI (8.4%). In conclusion, conversion to everolimus at 10-14 weeks posttransplant was associated with renal function similar to that with standard therapy overall. Rates of BPAR were low in all groups, but lower with tacrolimus than everolimus open de Fijter JW, Holdaas H, Øyen O, Sanders JS, Sundar S, Bemelman FJ, Sommerer C, Pascual J, Avihingsanon Y, Pongskul C, Oppenheimer F, Toselli L, Russ G, Wang Z, Lopez P, Kochuparampil J, Cruzado JM, van der Giet M; ELEVATE Study Group: [...; Guido Garosi; Paolo Rigotti; Giuseppe Tisone; Paola Todeschini; ...] de Fijter JW, Holdaas H, Øyen O, Sanders JS, Sundar S, Bemelman FJ, Sommerer C, Pascual J, Avihingsanon Y, Pongskul C, Oppenheimer F, Toselli L, Russ G, Wang Z, Lopez P, Kochuparampil J, Cruzado JM, van der Giet M; ELEVATE Study Group: [..; Guido Garosi; Paolo Rigotti; Giuseppe Tisone; Paola Todeschini; ..]

Published
2017

40. Pretransplant identification of acute rejection risk following kidney transplantation

Author

Lebranchu, Y. (Yvon), Baan, C.C. (Carla), Biancone, L. (Luigi), Legendre, C. (Christophe), Morales, J.M. (José Maria), Naesens, L., Thomusch, O. (Oliver), Friend, P. (Peter), Lebranchu, Y. (Yvon), Baan, C.C. (Carla), Biancone, L. (Luigi), Legendre, C. (Christophe), Morales, J.M. (José Maria), Naesens, L., Thomusch, O. (Oliver), and Friend, P. (Peter)

Abstract

Lack of an accepted definition for 'high immunological risk' hampers individualization of immunosuppressive therapy after kidney transplantation. For recipient-related risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor. Conventional immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant anti-HLA alloantibodies, and panel reactive antibodies) are being reassessed in light of growing understanding about the role of donor-specific antibodies (DSA). At the time of transplant, delayed graft function is one of the most clear-cut risk factors for acute rejection. Extended cold ischemia time (≥24 h) may also play a contributory role. While it is not yet possible to establish conclusively the relative contribution of different risk factors for acute rejection after kidney transplantation, the available data point to variables that should be taken into account at the time of transplant. Together, these offer a realistic basis for planning an appropriate immunosuppression regimen in individual patients.

Published
2014
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41. Pretransplant identification of acute rejection risk following kidney transplantation

Author

Lebranchu, Y, Baan, Carla, Biancone, L, Legendre, C, Morales, JM, Naesens, M, Thomusch, O, Friend, P, Lebranchu, Y, Baan, Carla, Biancone, L, Legendre, C, Morales, JM, Naesens, M, Thomusch, O, and Friend, P

Abstract

Lack of an accepted definition for high immunological risk' hampers individualization of immunosuppressive therapy after kidney transplantation. For recipient-related risk factors for acute rejection, the most compelling evidence points to younger age and African American ethnicity. Recipient gender, body mass, previous transplantation, and concomitant infection or disease do not appear to be influential. Deceased donation now has only a minor effect on rejection risk, but older donor age remains a significant predictor. Conventional immunological markers (human leukocyte antigen [HLA] mismatching, pretransplant anti-HLA alloantibodies, and panel reactive antibodies) are being reassessed in light of growing understanding about the role of donor-specific antibodies (DSA). At the time of transplant, delayed graft function is one of the most clear-cut risk factors for acute rejection. Extended cold ischemia time (24h) may also play a contributory role. While it is not yet possible to establish conclusively the relative contribution of different risk factors for acute rejection after kidney transplantation, the available data point to variables that should be taken into account at the time of transplant. Together, these offer a realistic basis for planning an appropriate immunosuppression regimen in individual patients.

Published
2014

42. TRANSPLANTATION BASIC SCIENCE, ALLOGENIC AND XENOGENIC TOLERANCE

Author

Berthelot, L., primary, Robert, T., additional, Tabary, T., additional, Vuiblet, V., additional, Drame, M., additional, Toupance, O., additional, Rieu, P., additional, Monteiro, R. C., additional, Toure, F., additional, Ferrario, S., additional, Cantaluppi, V., additional, De Lena, M., additional, Dellepiane, S., additional, Beltramo, S., additional, Rossetti, M., additional, Manzione, A. M., additional, Messina, M., additional, Gai, M., additional, Dolla, C., additional, Biancone, L., additional, Camussi, G., additional, Pontrelli, P., additional, Oranger, A. R., additional, Accetturo, M., additional, Rascio, F., additional, Gigante, M., additional, Castellano, G., additional, Schena, A., additional, Fiorentino, M., additional, Zito, A., additional, Zaza, G., additional, Stallone, G., additional, Gesualdo, L., additional, Grandaliano, G., additional, Pattonieri, E. F., additional, Gregorini, M., additional, Corradetti, V., additional, Rocca, C., additional, Milanesi, S., additional, Peloso, A., additional, Ferrario, J., additional, Cannone, M., additional, Bosio, F., additional, Maggi, N., additional, Avanzini, M. A., additional, Minutillo, P., additional, Paulli, M., additional, Maestri, M., additional, Rampino, T., additional, Dal Canton, A., additional, Wu, K. S. T., additional, Coxall, O., additional, Luque, Y., additional, Candon, S., additional, Rabant, M., additional, Noel, L.-H., additional, Thervet, E., additional, Chatenoud, L., additional, Snanoudj, R., additional, Anglicheau, D., additional, Legendre, C., additional, Zuber, J., additional, Hruba, P., additional, Brabcova, I., additional, Krepsova, E., additional, Slatinska, J., additional, Sekerkova, A., additional, Striz, I., additional, Zachoval, R., additional, Viklicky, O., additional, Scholbach, T. M., additional, Wang, H.-K., additional, Loong, C.-C., additional, Yang, A.-H., additional, Wu, T.-H., additional, Guberina, H., additional, Rebmann, V., additional, Dziallas, P., additional, Dolff, S., additional, Wohlschlaeger, J., additional, Heinemann, F. M., additional, Witzke, O., additional, Zoet, Y. M., additional, Claas, F. H. J., additional, Horn, P. A., additional, Kribben, A., additional, Doxiadis, I. I. N., additional, Prasad, N., additional, Yadav, B., additional, Agarwal, V., additional, Jaiswal, A., additional, Rai, M., additional, Hope, C. M., additional, Coates, P. T., additional, Heeger, P. S., additional, Carroll, R., additional, Masola, V., additional, Secchi, M. F., additional, Onisto, M., additional, Gambaro, G., additional, Lupo, A., additional, Matsuyama, M., additional, Kobayashi, T., additional, Yoneda, Y., additional, Chargui, J., additional, Touraine, J. L., additional, Yoshimura, R., additional, Vizza, D., additional, Perri, A., additional, Lupinacci, S., additional, Toteda, G., additional, Lofaro, D., additional, Leone, F., additional, Gigliotti, P., additional, La Russa, A., additional, Papalia, T., additional, Bonofilgio, R., additional, Sentis Fuster, A., additional, Kers, J., additional, Yapici, U., additional, Claessen, N., additional, Bemelman, F. J., additional, Ten Berge, I. J. M., additional, Florquin, S., additional, Glotz, D., additional, Rostaing, L., additional, Squifflet, J.-P., additional, Merville, P., additional, Belmokhtar, C., additional, Le Ny, G., additional, Lebranchu, Y., additional, Papazova, D. A., additional, Friederich-Persson, M., additional, Koeners, M. P., additional, Joles, J. A., additional, Verhaar, M. C., additional, Trivedi, H. L., additional, Vanikar, A. V., additional, Dave, S. D., additional, Suarez Alvarez, B., additional, Garcia Melendreras, S., additional, Carvajal Palao, R., additional, Diaz Corte, C., additional, Ruiz Ortega, M., additional, Lopez-Larrea, C., additional, Yadav, A. K., additional, Bansal, D., additional, Kumar, V., additional, Minz, M., additional, Jha, V., additional, Kaminska, D., additional, Koscielska-Kasprzak, K., additional, Chudoba, P., additional, Mazanowska, O., additional, Banasik, M., additional, Zabinska, M., additional, Boratynska, M., additional, Lepiesza, A., additional, Korta, K., additional, Klinger, M., additional, Csohany, R., additional, Prokai, A., additional, Pap, D., additional, Balicza-Himer, N., additional, Vannay, A., additional, Fekete, A., additional, Kis-Petik, K., additional, Peti-Peterdi, J., additional, Szabo, A., additional, Masajtis-Zagajewska, A., additional, Muras, K., additional, Niewodniczy, M., additional, Nowicki, M., additional, Pascual, J., additional, Srinivas, T. R., additional, Chadban, S., additional, Citterio, F., additional, Henry, M., additional, Oppenheimer, F., additional, Lee, P.-C., additional, Tedesco-Silva, H., additional, Zeier, M., additional, Watarai, Y., additional, Dong, G., additional, Hexham, M., additional, Bernhardt, P., additional, Vincenti, F., additional, Rocchetti, M. T., additional, Su owicz, J., additional, Wojas-Pelc, A., additional, Ignacak, E., additional, Janda, K., additional, Krzanowski, M., additional, Su owicz, W., additional, Mitsuhashi, M., additional, Murakami, T., additional, Benso, A., additional, Leuning, D., additional, Reinders, M., additional, Lievers, E., additional, Duijs, J., additional, Van Zonneveld, A. J., additional, Van Kooten, C., additional, Engelse, M., additional, Rabelink, T., additional, Assounga, A., additional, Omarjee, S., additional, Ngema, Z., additional, Ersoy, A., additional, Gultepe, A., additional, Isiktas Sayilar, E., additional, Akalin, H., additional, Coskun, F., additional, Oner Torlak, M., additional, Ayar, Y., additional, Riegersperger, M., additional, Plischke, M., additional, Steinhauser, C., additional, Jallitsch-Halper, A., additional, Sengoelge, G., additional, Winkelmayer, W. C., additional, Sunder-Plassmann, G., additional, Foedinger, M., additional, Kaziuk, M., additional, Kuz'Niewski, M., additional, B Tkowska- Prokop, A., additional, Pa Ka, K., additional, Dumnicka, P., additional, Kolber, W., additional, and Su Owicz, W., additional

Published
2014
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43. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

Author

Legendre, C.M., Licht, C., Muus, P., Greenbaum, L.A., Babu, S., Bedrosian, C., Bingham, C., Cohen, D.J., Delmas, Y., Douglas, K., Eitner, F., Feldkamp, T., Fouque, D., Furman, R.R., Gaber, O., Herthelius, M., Hourmant, M., Karpman, D., Lebranchu, Y., Mariat, C., Menne, J., Moulin, B., Nurnberger, J., Ogawa, M., Remuzzi, G., Richard, T., Sberro-Soussan, R., Severino, B., Sheerin, N.S., Trivelli, A., Zimmerhackl, L.B., Goodship, T., Loirat, C., Legendre, C.M., Licht, C., Muus, P., Greenbaum, L.A., Babu, S., Bedrosian, C., Bingham, C., Cohen, D.J., Delmas, Y., Douglas, K., Eitner, F., Feldkamp, T., Fouque, D., Furman, R.R., Gaber, O., Herthelius, M., Hourmant, M., Karpman, D., Lebranchu, Y., Mariat, C., Menne, J., Moulin, B., Nurnberger, J., Ogawa, M., Remuzzi, G., Richard, T., Sberro-Soussan, R., Severino, B., Sheerin, N.S., Trivelli, A., Zimmerhackl, L.B., Goodship, T., and Loirat, C.

Abstract

Item does not contain fulltext, BACKGROUND: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. METHODS: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). RESULTS: A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. CONCLUSIONS: Eculizumab inhibited complement-mediated

Published
2013

44. Terminal Complement Inhibitor Eculizumab in Atypical Hemolytic-Uremic Syndrome

Author

Legendre, C. M., Licht, C., Muus, P., Greenbaum, L. A., Babu, S., Bedrosian, C., Bingham, C., Cohen, D. J., Delmas, Y., Douglas, K., Eitner, F., Feldkamp, T., Fouque, D., Furman, R. R., Gaber, O., Herthelius, M., Hourmant, M., Karpman, Diana, Lebranchu, Y., Mariat, C., Menne, J., Moulin, B., Nuernberger, J., Ogawa, M., Remuzzi, G., Richard, T., Sberro-Soussan, R., Severino, B., Sheerin, N. S., Trivelli, A., Zimmerhackl, L. B., Goodship, T., Loirat, C., Legendre, C. M., Licht, C., Muus, P., Greenbaum, L. A., Babu, S., Bedrosian, C., Bingham, C., Cohen, D. J., Delmas, Y., Douglas, K., Eitner, F., Feldkamp, T., Fouque, D., Furman, R. R., Gaber, O., Herthelius, M., Hourmant, M., Karpman, Diana, Lebranchu, Y., Mariat, C., Menne, J., Moulin, B., Nuernberger, J., Ogawa, M., Remuzzi, G., Richard, T., Sberro-Soussan, R., Severino, B., Sheerin, N. S., Trivelli, A., Zimmerhackl, L. B., Goodship, T., and Loirat, C.

Abstract

Background Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease. Methods We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases. Patients with low platelet counts and renal damage (in trial 1) and those with renal damage but no decrease in the platelet count of more than 25% for at least 8 weeks during plasma exchange or infusion (in trial 2) were recruited. The primary end points included a change in the platelet count (in trial 1) and thrombotic microangiopathy event-free status (no decrease in the platelet count of >25%, no plasma exchange or infusion, and no initiation of dialysis) (in trial 2). Results A total of 37 patients (17 in trial 1 and 20 in trial 2) received eculizumab for a median of 64 and 62 weeks, respectively. Eculizumab resulted in increases in the platelet count; in trial 1, the mean increase in the count from baseline to week 26 was 73x10(9) per liter (P<0.001). In trial 2, 80% of the patients had thrombotic microangiopathy event-free status. Eculizumab was associated with significant improvement in all secondary end points, with continuous, time-dependent increases in the estimated glomerular filtration rate (GFR). In trial 1, dialysis was discontinued in 4 of 5 patients. Earlier intervention with eculizumab was associated with significantly greater improvement in the estimated GFR. Eculizumab was also associated with improvement in health-related quality of life. No cumulative toxicity of therapy or serious infection-related adverse events, including meningococcal infections, were observed through the extension period. Conclusions Eculizumab inhibited complement-mediated thr

Published
2013

45. Geographical prevalence, risk factors and impact of hepatitis B and C after renal transplantation

Author

Kliem, V, Michel, U, Burg, M, Bock, A, Chapman, J, Dussol, B, Fritsche, L, Lebranchu, Y, Oppenheimer, F, Pohanka, E, Salvadori, M, Tufveson, Gunnar, Kliem, V, Michel, U, Burg, M, Bock, A, Chapman, J, Dussol, B, Fritsche, L, Lebranchu, Y, Oppenheimer, F, Pohanka, E, Salvadori, M, and Tufveson, Gunnar

Abstract

BACKGROUND: Hepatitis B (HBV) and hepatitis C (HCV) virus infections are major risk factors affecting long-term morbidity and mortality after renal transplantation. Hepatitis prevalence is subject to geographical variations. OBJECTIVE: To compare and analyze the geographical prevalence, risk factors and impact of HBV and HCV infection in multinational cohorts of renal transplant recipients. METHODS: From 1989 - 2002, data on 12,856 kidney transplant recipients in 37 countries were collected within the prospective MOST (Multinational Observational Study in Transplantation). Subgroup analyses of hepatitis-related prevalence, risk factors and impact were conducted on patients whose HBV and HCV status was available at time of transplantation. Countries were substratified according to population prevalence of > or = 5% HBV or > or = 10% HCV. RESULTS: The prevalence of HBV was 2.9%, of HCV 8.7% and of HBV together with HCV 0.4%. Risk factors for hepatitis infection in renal transplant recipients were long dialysis time, retransplantation and blood transfusions. At each study endpoint up to 5 years after transplantation, no significant differences in graft function were observed, although the 1-year acute rejection rate tended to be lower in HCV+ patients. At 5 years post-transplant, there were no differences between the subgroups and regions regarding infections, post-transplant diabetes mellitus or malignancies including PTLD. CONCLUSIONS: Overall, HCV infections are more prevalent than HBV. Despite large geographical differences in prevalence, HBV and HCV status did not appear to have a significant impact on renal graft function, infections, malignancies and post-transplant diabetes mellitus up to 5 years after renal transplantation throughout the MOST countries.

Published
2009

46. Mutations in STAT3 and IL12RB1 impair the development of human IL-17-producing T cells

Author

de Beaucoudrey, L, Puel, A, Filipe-Santos, O, Cobat, A, Ghandil, P, Chrabieh, M, Feinberg, J, von Bernuth, H, Samarina, A, Jannière, L, Fieschi, C, Stéphan, J L, Boileau, C, Lyonnet, S, Jondeau, G, Cormier-Daire, V, Le Merrer, M, Hoarau, C, Lebranchu, Y, Lortholary, O, Chandesris, M O, Tron, F, Gambineri, E, Bianchi, L, Rodriguez-Gallego, C, Zitnik, S E, Vasconcelos, J, Guedes, M, Vitor, A B, Marodi, L, Chapel, H, Reid, B, Roifman, C, Nadal, D, Reichenbach, J, Caragol, I, Garty, B Z, Dogu, F, Camcioglu, Y, Gülle, S, Sanal, O, Fischer, A, Abel, L, Stockinger, B, Picard, C, Casanova, J L, de Beaucoudrey, L, Puel, A, Filipe-Santos, O, Cobat, A, Ghandil, P, Chrabieh, M, Feinberg, J, von Bernuth, H, Samarina, A, Jannière, L, Fieschi, C, Stéphan, J L, Boileau, C, Lyonnet, S, Jondeau, G, Cormier-Daire, V, Le Merrer, M, Hoarau, C, Lebranchu, Y, Lortholary, O, Chandesris, M O, Tron, F, Gambineri, E, Bianchi, L, Rodriguez-Gallego, C, Zitnik, S E, Vasconcelos, J, Guedes, M, Vitor, A B, Marodi, L, Chapel, H, Reid, B, Roifman, C, Nadal, D, Reichenbach, J, Caragol, I, Garty, B Z, Dogu, F, Camcioglu, Y, Gülle, S, Sanal, O, Fischer, A, Abel, L, Stockinger, B, Picard, C, and Casanova, J L

Abstract

The cytokines controlling the development of human interleukin (IL) 17--producing T helper cells in vitro have been difficult to identify. We addressed the question of the development of human IL-17--producing T helper cells in vivo by quantifying the production and secretion of IL-17 by fresh T cells ex vivo, and by T cell blasts expanded in vitro from patients with particular genetic traits affecting transforming growth factor (TGF) beta, IL-1, IL-6, or IL-23 responses. Activating mutations in TGFB1, TGFBR1, and TGFBR2 (Camurati-Engelmann disease and Marfan-like syndromes) and loss-of-function mutations in IRAK4 and MYD88 (Mendelian predisposition to pyogenic bacterial infections) had no detectable impact. In contrast, dominant-negative mutations in STAT3 (autosomal-dominant hyperimmunoglobulin E syndrome) and, to a lesser extent, null mutations in IL12B and IL12RB1 (Mendelian susceptibility to mycobacterial diseases) impaired the development of IL-17--producing T cells. These data suggest that IL-12Rbeta1- and STAT-3--dependent signals play a key role in the differentiation and/or expansion of human IL-17-producing T cell populations in vivo.

Published
2008

47. Genetic diseases and molecular genetics

Author

Legendre, C., primary, Cohen, D., additional, Delmas, Y., additional, Feldkamp, T., additional, Fouque, D., additional, Furman, R., additional, Gaber, O., additional, Greenbaum, L., additional, Goodship, T., additional, Haller, H., additional, Herthelius, M., additional, Hourmant, M., additional, Licht, C., additional, Moulin, B., additional, Sheerin, N., additional, Trivelli, A., additional, Bedrosian, C. L., additional, Loirat, C., additional, Legendre, C., additional, Babu, S., additional, Jungraithmayr, T., additional, Lebranchu, Y., additional, Riedl, M., additional, Gaber, A. O., additional, Bedrosian, C., additional, Muus, P., additional, Douglas, K., additional, Remuzzi, G., additional, Kourouklaris, A., additional, Ioannou, K., additional, Athanasiou, I., additional, Demetriou, K., additional, Panagidou, A., additional, Zavros, M., additional, Rodriguez C, N. Y., additional, Blasco, M., additional, Arcal, C., additional, Quintana, L. F., additional, Rodriguez de Cordoba, S., additional, Campistol, J. M., additional, Bachmann, N., additional, Eisenberger, T., additional, Decker, C., additional, Bolz, H. J., additional, Bergmann, C., additional, Pesce, F., additional, Cox, S. N., additional, Serino, G., additional, De Palma, G., additional, Sallustio, F. P., additional, Schena, F., additional, Falchi, M., additional, Pieri, M., additional, Stefanou, C., additional, Zaravinos, A., additional, Erguler, K., additional, Lapathitis, G., additional, Dweep, H., additional, Sticht, C., additional, Anastasiadou, N., additional, Zouvani, I., additional, Voskarides, K., additional, Gretz, N., additional, Deltas, C. C., additional, Ruiz, A., additional, Bonny, O., additional, Sallustio, F., additional, Curci, C., additional, Cox, S., additional, Kemter, E., additional, Sklenak, S., additional, Aigner, B., additional, Wanke, R., additional, Kitzler, T. M., additional, Moskowitz, J. L., additional, Piret, S. E., additional, Lhotta, K., additional, Tashman, A., additional, Velez, E., additional, Thakker, R. V., additional, Kotanko, P., additional, Leierer, J., additional, Rudnicki, M., additional, Perco, P., additional, Koppelstaetter, C., additional, Mayer, G., additional, Sa, M. J. N., additional, Alves, S., additional, Storey, H., additional, Flinter, F., additional, Willems, P. J., additional, Carvalho, F., additional, Oliveira, J., additional, Arsali, M., additional, Papazachariou, L., additional, Demosthenous, P., additional, Lazarou, A., additional, Hadjigavriel, M., additional, Stavrou, C., additional, Yioukkas, L., additional, Deltas, C., additional, Pierides, A., additional, Kkolou, M., additional, Toka, H. R., additional, Dibartolo, S., additional, Lanske, B., additional, Brown, E. M., additional, Pollak, M. R., additional, Familiari, A., additional, Zavan, B., additional, Sanna Cherchi, S., additional, Fabris, A., additional, Cristofaro, R., additional, Gambaro, G., additional, D'Angelo, A., additional, Anglani, F., additional, Toka, H., additional, Mount, D., additional, Pollak, M., additional, Curhan, G., additional, Sengoge, G., additional, Bajari, T., additional, Kupczok, A., additional, von Haeseler, A., additional, Schuster, M., additional, Pfaller, W., additional, Jennings, P., additional, Weltermann, A., additional, Blake, S., additional, Sunder-Plassmann, G., additional, Kerti, A., additional, Csohany, R., additional, Wagner, L., additional, Javorszky, E., additional, Maka, E., additional, Tulassay, T., additional, Tory, K., additional, Kingswood, J., additional, Nikolskaya, N., additional, Mbundi, J., additional, Jozwiak, S., additional, Belousova, E., additional, Frost, M., additional, Kuperman, R., additional, Bebin, M., additional, Korf, B., additional, Flamini, R., additional, Kohrman, M., additional, Sparagana, S., additional, Wu, J., additional, Brechenmacher, T., additional, Stein, K., additional, Bissler, J., additional, Franz, D., additional, Zonnenberg, B., additional, Cheung, W., additional, Wang, J., additional, Lam, D., additional, Budde, K., additional, Ivanitskiy, L., additional, Sowershaewa, E., additional, Krasnova, T., additional, Samokhodskaya, L., additional, Safarikova, M., additional, Jana, R., additional, Jitka, S., additional, Obeidova, L., additional, Kohoutova, M., additional, Tesar, V., additional, Evrengul, H., additional, Ertan, P., additional, Serdaroglu, E., additional, Yuksel, S., additional, Mir, S., additional, Yang n Ergon, E., additional, Berdeli, A., additional, Zawada, A., additional, Rogacev, K., additional, Rotter, B., additional, Winter, P., additional, Fliser, D., additional, Heine, G., additional, Bataille, S., additional, Moal, V., additional, Berland, Y., additional, Daniel, L., additional, Rosado, C., additional, Bueno, E., additional, Fraile, P., additional, Lucas, C., additional, Garcoa-Cosmes, P., additional, Tabernero, J. M., additional, Gonzalez, R., additional, Garcia-Cosmes, P., additional, Silska-Dittmar, M., additional, Zaorska, K., additional, Malke, A., additional, Musielak, A., additional, Ostalska-Nowicka, D., additional, Zachwieja, J., additional, K d r, V., additional, Uz, E., additional, Yigit, A., additional, Altuntas, A., additional, Yigit, B., additional, Inal, S., additional, Sezer, M., additional, Yilmaz, R., additional, Visciano, B., additional, Porto, C., additional, Acampora, E., additional, Russo, R., additional, Riccio, E., additional, Capuano, I., additional, Parenti, G., additional, Pisani, A., additional, Feriozzi, S., additional, Perrin, A., additional, West, M., additional, Nicholls, K., additional, Torras, J., additional, Cybulla, M., additional, Conti, M., additional, Angioi, A., additional, Floris, M., additional, Melis, P., additional, Asunis, A. M., additional, Piras, D., additional, Pani, A., additional, Warnock, D., additional, Guasch, A., additional, Thomas, C., additional, Wanner, C., additional, Campbell, R., additional, Vujkovac, B., additional, Okur, I., additional, Biberoglu, G., additional, Ezgu, F., additional, Tumer, L., additional, Hasanoglu, A., additional, Bicik, Z., additional, Akin, Y., additional, Mumcuoglu, M., additional, Ecder, T., additional, Paliouras, C., additional, Mattas, G., additional, Papagiannis, N., additional, Ntetskas, G., additional, Lamprianou, F., additional, Karvouniaris, N., additional, and Alivanis, P., additional

Published
2013
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49. Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function : an insight from MOST, a multinational observational study.

Author

Salvadori, M, Rosati, A, Bertoni, E, Bock, A, Chapman, J, Dussol, B, Fritsche, L, Kliem, V, Lebranchu, Y, Oppenheimer, F, Pohanka, E, Tufveson, G, Soergel, M, Salvadori, M, Rosati, A, Bertoni, E, Bock, A, Chapman, J, Dussol, B, Fritsche, L, Kliem, V, Lebranchu, Y, Oppenheimer, F, Pohanka, E, Tufveson, G, and Soergel, M

Published
2006

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