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1. Paternity in male kidney transplant recipients: a French national survey, the PATeRNAL study

Author

Annabel Boyer, Thierry Lobbedez, Mohamed Ouethrani, Angélique Thuillier Lecouf, Nicolas Bouvier, Valérie Châtelet, Bruno Hurault de Ligny, and On behalf of the Spiesser transplant group

Subjects
Paternity, Kidney transplant, Pregnancy, Congenital malformation, Immunosuppression, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background There is concern about the impact of immunosuppressive agents taken by male kidney transplant (KT) recipients on the risk of foetal malformations. The aim of our survey was to estimate the paternity rate and the outcomes of pregnancies fathered by kidney transplanted males. Methods This survey analysed 1332 male KT recipients older than 18 years, followed in 13 centres in France. A self-reported questionnaire was used to collect data on the patients, treatments at the time of conception and the pregnancy outcomes. Results The study included data on 349 children from 404 pregnancies fathered by 232 male KT recipients. The paternity rate was 17% (95% CI [15–20]). There were 37 (9%, 95% CI [7–12]) spontaneous abortions, 12 (3%, 95% CI [2–5]) therapeutic abortions, 2 (0.5%, 95% CI [0.1–1]) still births, and 13 (4%, 95% CI [2–6]) malformations reported. Compared to the general population, there was no difference in the proportion of congenital malformations nor unwanted outcomes whether the father was exposed or not to immunosuppressive agents. Conclusions This survey does not provide any warning signal that pregnancies fathered by male patients exposed to immunosuppressive agents, notably the debated MMF/MPA, have more complications than pregnancies in the general population.

Published
2020
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2. Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years

Author

Mathilde Lemoine, Dimitri Titeca Beauport, Thierry Lobbedez, Gabriel Choukroun, Bruno Hurault de Ligny, Marc Hazzan, Dominique Guerrot, and Dominique Bertrand

Subjects
Diseases of the genitourinary system. Urology, RC870-923
Abstract

Introduction: Although kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population. Methods: All patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included (n = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death. Results: The mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08–4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18–4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04–4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22–6.3), and acute rejection (OR 2.77; 95% CI 1.2–6.3). Conclusion: In kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival. Keywords: cardiovascular disease, elderly, graft failure, infectious disease, kidney transplantation, patient death

Published
2019
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3. Lymphomatoid Granulomatosis Treated Successfully with Rituximab in a Renal Transplant Patient

Author

Cindy Castrale, Wael El Haggan, Françoise Chapon, Oumedaly Reman, Thierry Lobbedez, Jean Philippe Ryckelynck, and Bruno Hurault de Ligny

Subjects
Surgery, RD1-811
Abstract

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

Published
2011
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4. The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Author

Friederike Petzold, Katy Billot, Xiaoyi Chen, Charline Henry, Emilie Filhol, Yoann Martin, Marina Avramescu, Maxime Douillet, Vincent Morinière, Pauline Krug, Cécile Jeanpierre, Kalman Tory, Olivia Boyer, Anita Burgun, Aude Servais, Remi Salomon, Alexandre Benmerah, Laurence Heidet, Nicolas Garcelon, Corinne Antignac, Mohamad Zaidan, Sophie Saunier, Tania Attié-Bitach, Valerie Comier-Daire, Jean-Michel Rozet, Yaacov Frishberg, Brigitte Llanas, Michel Broyer, Nabil Mohsin, Marie-Alice Macher, Nicole Philip, Véronique Baudouin, Damian Brackman, Chantal Loirat, Marina Charbit, Maud Dehennault, Claude Guyot, Pierre Bataille, Mariet Elting, Georges Deschenes, Andrea Gropman, Geneviève Guest, Marie-France Gagnadoux, Philippe Nicoud, Pierre Cochat, Bruno Ranchin, Albert Bensman, Anne-Marie Guerrot, Bertrand Knebelmann, Ilmay Bilge, Danièle Bruno, Stéphane Burtey, Caroline Rousset Rouvière, Valérie Caudwell, Denis Morin, Hélène Dollfus, Anne Maisin, Christian Hamel, Eric Bieth, Sophie Gie, Judith Goodship, Gwenaelle Roussey, Hermine La Selve, Hubert Nivet, Lucie Bessenay, Mathilde Caillez, Jean Bernard Palcoux, Stéphane Benoît, Philippe Dubot, Marc Fila, Fabienne Giuliano, Daouya Iftene, Michele Kessler, Theresa Kwon, Anine Lahoche, Audrey Laurent, Anne-Laure Leclerc, David Milford, Thomas Neuhaus, Sylvie Odent, Philippe Eckart, Dominique Chauveau, Patrick Niaudet, Horacio Repetto, Sophie Taque, Alexandra Bruel, Alexandra Noel-Botte, Emma Allain Launay, Lisa Allard, Dany Anlicheau, Anne-Laure Adra, Arnaud Garnier, Arvind Nagra, Remy Baatard, Justine Bacchetta, Banu Sadikoglu, Christine Barnerias, Anne Barthelemy, Lina Basel, Nader Bassilios, Hedi Ben Maiz, Fatma Ben Moussa, Faïza Benmati, Romain Berthaud, Aurélia Bertholet, Dominique Blanchier, Jean Jacques Boffa, Karim Bouchireb, Ihab Bouhabel, Zakaria Boukerroucha, Guylhène Bourdat-Michel, Odile Boute, Karine Brochard, Roseline Caumes, Siham Chafai Elalaoui, Bernard Chamontin, Marie Caroline Chastang, Christine Pietrement, Christine Richer, Christophe Legendre, Karin Dahan, Fabienne Dalla-Vale, Damien Thibaudin, Maxime Dauvergne, Salandre Davourie, Martin Debeukelaer, Jean Daniel Delbet, Constantinos Deltas, Denis Graber, Nadège Devillars, Boucar Diouf, Martine Doco Fenzy, Jean-Luc André, Dominique Joly, Alan Fryer, Laetitia Albano, Elisabeth Cassuto, Aline Pincon, Ana Medeira, Annabelle Chaussenot, Anne Mensire-Marinier, Francois Bouissou, Stephane Decramer, Armand Bottani, Aurélie Hummel, Alexandre Karras, Avi Katz, Christine Azema, Bénédicte Janbon, Bernard Roussel, Claude Bonniol, Christiophe Mariat, Gérard Champion, Deborah Chantreuil, Nicolas Chassaing, Christiane Mousson, Christine Baudeau, Delphine Hafdar Cuntz, Cyril Mignot, Laurene Dehoux, Didier Lacombe, Thierry Hannedouche, Elodie Mérieau, Emmanuelle Charlin, Eric Gauthier, Florent Plasse, Stanislas Faguer, Fanny Lebas, Florence Demurger, Francesco Emma, François Cartault, Geneviève Dumont, Nathalie Godefroid, Vincent Guigonis, Sophie Hillaire, Jaap Groothoff, Jan Dudley, Noémie Jourde-Chiche, Khalil El Karoui, Saoussen Krid, Krier Coudert, Larbi Bencheick, Laurent Yver, Marie-Pierre Lavocat, Le Monies De Sagazan, Valerie Leroy, Lise Thibaudin, Liz Ingulli, Lorraine Gwanmesia, Lydie Burglen, Marie-Hélène Saïd-Menthon, Marta Carrera, Mathilde Nizon, Catherine Melander, Michel Foulard, Monique Blayo, Jacques Prinseau, Nadine Jay, Nathalie Brun, Nicolas Camille, François Nobili, Olivier Devuyst, Ouafa Ben Brahim, Paloma Parvex, Laurence Perrin Sabourin, Philippe Blanc, Philippe Vanhille, Pierre Galichon, Sophie Pierrepont, Vincent Planquois, Gwenaelle Poussard, Claire Pouteil Noble, Radia Allal, Raphaelle Bernard, Raynaud Mounet, Rémi Cahen, Renaud Touraine, Claire Rigothier, Amélie Ryckewaert, Mathieu Sacquepee, Salima El Chehadeh, Charlotte Samaille, Shuman Haq, Ari Simckes, Stéphanie Lanoiselée, Stephanie Tellier, Jean-François Subra, Sylvie Cloarec, Julie Tenenbam, Thomas Lamy, Valérie Drouin Garraud, Huguette Valette, Vanina Meyssonnier, Rosa Vargas-Poussou, Yves Snajer, Sandrine Durault, Emmanuelle Plaisier, Etienne Berard, Fadi Fakhouri, Ferielle Louillet, Paul Finielz, Michel Fischbach, Bernard Foliguet, Hélène Francois-Pradier, Florentine Garaix, Marion Gerard, Gianfranco Rizzoni, Brigitte Gilbert, Denis Glotz, Astrid Godron Dubrasquet, Jean-Pierre Grünfeld, Guillaume Bollee, Michelle Hall, Sverker Hansson, Damien Haye, Hélène Taffin, Friedhelm Hildebrandt, Maryvonne Hourmand, Hümya Kayserili, Ivan Tack, Marie Line Jacquemont, Jennifer Fabre-Teste, Cliff Kashtan, Kkoen Van Hoeck, Alexandre Klein, Yannick Knefati, Nine Knoers, Martin Konrad, Alain Lachaux, Isabelle Landru, Gilbert Landthaler, Philippe Lang, Patrick Le Pogamp, Tristan Legris, Catherine Didailler, Thierry Lobbedez, Loïc de Parscau, Lucile Pinson, Hervé Maheut, Marc Duval-Arnould, Marlène Rio, Marie-Claire Gubler, Pierre Merville, Guillaume Mestrallet, Maite Meunier, Karine Moreau, Jérôme Harambat, Graeme Morgan, Georges Mourad, Niksic Stuber, Odile Boespflug-Tanguy, Olivier Dunand, Olivier Niel, Nacera Ouali, Paolo Malvezzi, Pauline Abou Jaoude, Solenne Pelletier, Julie Peltier, M.B. Petersen, Philippe Michel, Philippe Rémy, Jean-Baptiste Philit, Valérie Pichault, Thierry Billette de Villemeur, Bernard Boudailliez, Bruno Leheup, Claire Dossier, Djamal-Dine Djeddi, Yves Berland, Bruno Hurault de Ligny, Susan Rigden, Christophe Robino, Annick Rossi, Sabine Sarnacki, Messaoud Saidani, Albane Brodin Sartorius, Elise Schäfer, Sztriha Laszlo, Marie-Christine Thouret, Angélique Thuillier-Lecouf, Howard Trachtman, Claire Trivin, Michel Tsimaratos, Rita Van Damme-Lombaerts, Marjolaine Willems, Michel Youssef, Ariane Zaloszyc, Alexis Zawodnik, and Marie-Julia Ziliotis

Subjects
Nephrology
Abstract

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease.

Published
2023
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5. Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

Author

Bénédicte Janbon, Sophie Caillard, Isabelle Jollet, Elisabeth Cassuto, Elodie Bailly, Bruno Hurault de Ligny, Michel Delahousse, Marc Hazzan, Anne Devys, Antoine Thierry, Pierre Merville, Sophie Girerd, Renaud Snanoudj, Dany Anglicheau, Vincent Vuiblet, Nassim Kamar, Kahina Amokrane, Philippe Grimbert, Eric Rondeau, Gabriel Choukroun, Alexandre Hertig, Marie Metzger, Jean-Luc Taupin, Yann Le Meur, Christophe Legendre, Emmanuel Morelon, Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Néphrologie et Transplantation [Strasbourg], Hôpital Civil [Strasbourg], CHU Strasbourg-CHU Strasbourg, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Etablissement français du sang [Poitiers] (EFS), Service de néphrologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Henri Mondor, Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Néphrologie [Amiens], CHU Amiens-Picardie-hôpital Sud, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Etablissement français du sang [Angers], Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Foch [Suresnes], Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France (Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de néphrologie et de transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Lymphocytes B, Autoimmunité et Immunothérapies (LBAI), and Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-LabEX IGO Immunothérapie Grand Ouest-Institut Brestois Santé Agro Matière (IBSAM)

Subjects
Adult, Graft Rejection, Male, 0301 basic medicine, Isoantigens, Allosensitization, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Population, 030232 urology & nephrology, kidney transplantation, Human leukocyte antigen, acute rejection, Epitope, 03 medical and health sciences, 0302 clinical medicine, Antigen, HLA-DQ Antigens, immunosuppression minimization, Humans, Transplantation, Homologous, Medicine, Everolimus, education, Kidney transplantation, education.field_of_study, biology, Drug Substitution, business.industry, Histocompatibility Testing, Patient Selection, Graft Survival, Immunosuppression, Middle Aged, epitopes, medicine.disease, HLA mismatching, 3. Good health, 030104 developmental biology, Nephrology, Immunology, Cyclosporine, antibody-mediated rejection, biology.protein, Female, Antibody, business, Immunosuppressive Agents, Follow-Up Studies
Abstract

International audience; Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.

Published
2019
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6. Néphropathie associée à une vascularite urticarienne hypocomplémentémique : présentation d’un cas clinique et revue de la littérature

Author

Nicolas Gautier, Antoine Lanot, A. Boyer, Bruno Hurault de Ligny, F. Comoz, Achille Aouba, Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Université de Caen Normandie - UFR Santé (UNICAEN Santé), Normandie Université (NU)-Normandie Université (NU), Laboratoire d'Anatomie Pathologique [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and Service de médecine interne [CHU Caen]

Subjects
Systemic disease, medicine.medical_specialty, medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Glomerulonephritis, Hydroxychloroquine, urologic and male genital diseases, medicine.disease, Dermatology, Sialadenitis, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Membranoproliferative glomerulonephritis, Biopsy, medicine, business, Nephritis, Systemic vasculitis, medicine.drug
Abstract

Hypocomplementemic urticarial vasculitis is a rare systemic vasculitis, affecting small vessels, characterised by chronicle urticaria, hypocomplementemia, and systemic manifestations. Renal involvement, whose prevalence varies between 9% and 60%, is mainly glomerular. We here report the case of a 59 years old woman presenting kidney failure, associated with chronicle urticaria and arthralgias. Laboratory investigation showed haematuria, proteinuria, hypocomplementemia and anti-SSa antibody positivity. A percutaneous kidney biopsy revealed focal and segmental glomerulonephritis associated with an acute interstitial nephritis. Hypocomplementemic urticarial vasculitis diagnosis was established after identifying anti-C1q antibodies. The lack of a dry syndrome, the negativity of a Schirmer test and the lack of sialadenitis on a salivary gland biopsy excluded an associated Gougerot-Sjogren Syndrome. The patient was treated with hydroxychloroquine and low-dose steroids, enabling a clinical and biological recovery. Of the 82 cases in the literature describing hypocomplementemic urticarial vasculitis associated nephropathies, 72 (88%) were a glomerular impairment, most frequently secondary to membranoproliferative glomerulonephritis. Only 6 (7%) tubulo-interstitial nephritis have been reported, 4 of them being associated with a glomerulonephritis. Patients were more likely to be women, aged in their third decade. The most frequent renal manifestations were haematuria (60%), and proteinuria (52%). Kidney failure was rarely observed (22%), with a fairly good renal prognosis. Hypocomplementemic urticarial vasculitis was associated with a systemic disease in 11 (13%) patients. In the absence of recommendations, the treatment strategy remains to be defined.

Published
2020
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7. Risk Factors for Early Graft Failure and Death After Kidney Transplantation in Recipients Older Than 70 Years

Author

Bruno Hurault de Ligny, Mathilde Lemoine, Marc Hazzan, Dominique Bertrand, Gabriel Choukroun, Dominique Guerrot, Dimitri Titeca Beauport, Thierry Lobbedez, Service de Néphrologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Réanimations [CHU Amiens-Picardie], CHU Amiens-Picardie, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie], Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Endothélium, valvulopathies et insuffisance cardiaque (EnVI), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Guerrot, Dominique

Subjects
medicine.medical_specialty, medicine.medical_treatment, graft failure, infectious disease, 030232 urology & nephrology, kidney transplantation, Disease, 030204 cardiovascular system & hematology, lcsh:RC870-923, elderly, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, cardiovascular disease, Internal medicine, medicine, Kidney transplantation, Ejection fraction, business.industry, Proportional hazards model, Immunosuppression, Odds ratio, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Confidence interval, 3. Good health, Transplantation, patient death, Nephrology, business
Abstract

Introduction Although kidney transplantation carries a survival benefit compared with dialysis, mortality, especially the first year after transplantation, is high in recipients older than 70. The aim of this study was to evaluate early death and graft failure, and to determine the risk factors associated with these events in this specific population. Methods All patients older than 70 years who received a kidney transplant between January 2000 and December 2014 in the North-West of France were included (n = 171). Baseline characteristics and outcomes after transplantation were studied. Kaplan-Meier analysis was performed to assess patient and graft survival, and Cox regression analysis to evaluate risk factors for graft failure and patient death. Results The mean recipient age was 73.3 ± 2.5 years. Death-censored graft survival at 1, 3, and 5 years were 82.6%, 78.7%, and 75.4%, respectively. Patient survival at 1, 3, and 5 years was 90.1%, 82.5%, and 68.1%, respectively. One year after transplantation, 17 patients (9.9%) were dead, mainly from infectious (58.5%) or cardiovascular disease (29.4%). According to the Cox multivariate analysis, the independent risk factors for death or graft failure during the first year were arrhythmia (odds ratio [OR] 2.26; 95% confidence interval [CI] 1.08–4.8), left-ventricular ejection fraction (LVEF) under 56% (OR 2.38; 95% CI 1.18–4.83), human leucocyte antigen (HLA) antibodies (OR 2.1; 95% CI 1.04–4.2), deceased donor from cardiovascular cause (OR 5.18; 95% CI 1.22–6.3), and acute rejection (OR 2.77; 95% CI 1.2–6.3). Conclusion In kidney transplant recipients older than 70 years, cardiac evaluation and immunosuppression optimization seem to be crucial to improve short-term patient and graft survival., Graphical abstract

Published
2019
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8. Does daily urine output really matter in renal transplantation?

Author

Alexis Desmonts, Henri Bensadoun, Arnaud Doerfler, Clement Orczyk, Xavier Tillou, Adrien Lee-Bion, Sophie Le Gal, and Bruno Hurault de Ligny

Subjects
Adult, Male, medicine.medical_specialty, Databases, Factual, Urinary system, medicine.medical_treatment, Urinary Bladder, Urology, Kidney, Postoperative Complications, medicine, Humans, Risk factor, Kidney transplantation, Dialysis, Aged, Transplantation, Proteinuria, business.industry, Graft Survival, General Medicine, Middle Aged, medicine.disease, Kidney Transplantation, Surgery, Relative risk, Female, medicine.symptom, Complication, business
Abstract

Summary Background: Our objective was to clarify the clinical outcome of renal transplantation based on residual daily urine output (RDUO). Material/Methods: We retrospectively analyzed a prospective database of 276 patients who underwent renal transplantation (Tx) between January 2008 and December 2012. Patients had pre-transplantation daily urine output measurement of 24-h proteinuria and were clinically re-evaluated the day before transplantation. We included patients with no daily urine output and those with residual daily urine output. Real bladder capacity was not measured. We excluded patients with a history of lower urinary tract malformation, those treated by trans-ileal conduit or enterocystoplasty, and those with early graft thrombosis or graft primary non-function. Results: Sex ratio, age at Tx, pre-Tx MHC antibodies levels, donor age, and cold ischemia duration were not significantly different between the 2 groups. Dialysis duration was longer in group I (p

Published
2013
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9. Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study

Author

Vincent Vuiblet, Guy Touchard, Marie Essig, Jean-Claude Aldigier, Antoine Thierry, Yann Lemeur, Vincent Javaugue, Bruno Hurault de Ligny, Ramzi Abou-Ayache, Isabelle Etienne, Charlotte Laurent, Frank Bridoux, Nicolas Bouvier, Elise Gand, Charlotte Colosio, Jean-Philippe Rerolle, Laure Ecotiere, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Rouen, Normandie Université (NU), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Sciences Pour l'Oenologie (SPO), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut de Recherche pour le Développement (IRD [Nouvelle-Calédonie])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de néphrologie - hémodialyse et transplantation rénale, Université Montpellier 1 (UM1)-Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), and Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Renal function, Azathioprine, Cyclosporins, 030230 surgery, Pharmacology, Risk Assessment, Mycophenolic acid, Statistics, Nonparametric, Nephropathy, Maintenance Chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Prospective Studies, Prospective cohort study, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Immunosuppression Therapy, Transplantation, business.industry, Graft Survival, Immunosuppression, Middle Aged, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Survival Analysis, 3. Good health, Treatment Outcome, Drug Therapy, Combination, Female, business, Immunosuppressive Agents, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Follow-Up Studies
Abstract

Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).

Published
2016
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10. Lymphomatoid Granulomatosis Treated Successfully with Rituximab in a Renal Transplant Patient

Author

Wael El Haggan, Oumedaly Reman, Jean Philippe Ryckelynck, Cindy Castrale, Françoise Chapon, Bruno Hurault de Ligny, and Thierry Lobbedez

Subjects
Pathology, medicine.medical_specialty, Lung, Lymphomatoid granulomatosis, business.industry, medicine.medical_treatment, lcsh:Surgery, Renal function, Case Report, Immunosuppression, lcsh:RD1-811, medicine.disease, Tacrolimus, Transplantation, medicine.anatomical_structure, Prednisone, medicine, Rituximab, business, medicine.drug
Abstract

Lymphomatoid granulomatosis (LYG) in renal transplant recipients is rare multisystemic angiocentric lymphoproliferative disorder with significant malignant potential. Here, we describe LYG in a 70-year-old renal allograft recipient who, 4 years after transplantation, on tacrolimus and mycophenolate mofetil and prednisone maintenance immunosuppression, complained of low-grade fever, persistent headache and gait disturbance. The MRI of the brain revealed diffuse periventricular cerebral and cerebellar contrast-enhanced lesions. The CT scan of the thorax showed multiple pulmonary nodular opacities in both lung fields. The patient was diagnosed LYG based on the cerebral biopsy showing perivascular infiltration of CD20-positive B-lymphocytes with granulomatous lesions and immunofluorescence staining with anti-EBV antibodies. With careful reduction of the immunossuppression combined with the use of rituximab, our patient showed a complete disappearance of LYG, and she is clinically well more than 4 years after the diagnosis, with good kidney function. No recurrence has been observed by radiological imaging until now. This is the first report of a durable (>4 years) complete remission of LYG after treatment with rituximab in renal transplantation.

Published
2011
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11. Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients

Author

Jeremy Bellien, Michel Godin, Robinson Joannides, Isabelle Etienne, Christian Thuillez, S. Barbier, Michele Iacob, Bruno Hurault de Ligny, and Yvon Lebranchu

Subjects
Transplantation, medicine.medical_specialty, business.industry, Urology, Renal function, medicine.disease, Surgery, Calcineurin, Hyperaemia, Blood pressure, medicine.anatomical_structure, Cyclosporin a, Medicine, medicine.symptom, Endothelial dysfunction, business, Artery
Abstract

Summary This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n = 15) or cyclosporin A (CsA, n = 14) associated with mycophenolate mofetil (MMF) and steroids (6 months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7 months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119 ± 3 vs. CsA: 138 ± 4 mmHg, P

Published
2010
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12. Kidney and Recipient Weight Incompatibility Reduces Long-Term Graft Survival

Author

Magali Giral, Pascal Daguin, Bruno Hurault de Ligny, Nathalie Trehet, Yohann Foucher, Jean-Paul Soulillou, Yann Labrune, Georges Karam, Carole Meyer, Karine Renaudin, François Bayle, M. Kessler, Anne Moreau, and Mathias Büchler

Subjects
Adult, Male, medicine.medical_specialty, Urology, Kidney, Cohort Studies, Risk Factors, medicine, Humans, Transplantation, Homologous, Kidney transplantation, Retrospective Studies, Transplantation, Proteinuria, business.industry, Body Weight, Graft Survival, Retrospective cohort study, Organ Size, General Medicine, Middle Aged, medicine.disease, Kidney Transplantation, Surgery, Treatment Outcome, surgical procedures, operative, medicine.anatomical_structure, Nephrology, Hypertension, Cohort, Female, Graft survival, medicine.symptom, business, Follow-Up Studies, Cohort study
Abstract

Long-term function of kidney allografts depends on multiple variables, one of which may be the compatibility in size between the graft and the recipient. Here, we assessed the long-term consequences of the ratio of the weight of the kidney to the weight of the recipient (KwRw ratio) in a multicenter cohort of 1189 patients who received a transplant between 1995 and 2006. The graft filtration rate increased by a mean of 5.74 ml/min between the third and sixth posttransplantation months among patients with a low KwRw ratio (

Published
2010
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13. A 50% reduction in cyclosporine exposure in stable renal transplant recipients: renal function benefits

Author

Bruno Hurault de Ligny, Jacques Benichou, Pierre-François Westeel, Pierre Marquet, Olivier Toupance, Michel Godin, Yannick Le Meur, Antoine Thierry, Marie-France Hellot, Azmi Al Najjar, Isabelle Etienne, and Arnaud François

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Urology, Renal function, Kidney Function Tests, Mycophenolic acid, Nephrotoxicity, Young Adult, chemistry.chemical_compound, Cadaver, Humans, Medicine, Tissue Distribution, Prospective Studies, Kidney transplantation, Aged, Transplantation, Creatinine, business.industry, Graft Survival, Middle Aged, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Tissue Donors, Surgery, Survival Rate, Treatment Outcome, chemistry, Nephrology, Area Under Curve, Cyclosporine, Kidney Failure, Chronic, Female, Hemodialysis, business, Immunosuppressive Agents, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease, medicine.drug
Abstract

Background. Although cyclosporine maintenance therapy reduces the risk of acute rejection and increases short-term graft survival in renal transplant recipients, its associated nephrotoxicity increases the risk of chronic graft dysfunction. The dose that allows an optimal risk-to-benefit ratio has not been established. Methods. This multicentre study enrolled stable renal allograft recipients receiving cyclosporine and mycophenolate mofetil without corticosteroids in their second year post-transplant. Patients were randomized to a cyclosporine dose targeted to a standard area under the concentration–time curve (AUC)0–12 h (usual exposure, n =1 04) or 50% of the study standard AUC0–12 h (low exposure, n = 108) using a three-point pharmacokinetic sampling. The primary endpoint was the percentage of patients with treatment failure at 24 months (graft loss/acute rejection/ nephrotoxicity/>15% serum creatinine level increase). Results. Treatment failure was reported in 37 out of 101 (37%) patients in the usual-exposure and 19 out of 106 (18%) patients in the low-exposure groups (P = 0.003). Mean estimated glomerular filtration rate decreased from baseline to 2 years with usual exposure and increased with low exposure (P < 0.001). Mean systolic and diastolic blood pressures were lower with low exposure (P = 0.03 and P = 0.008, respectively). Conclusion. In renal transplant recipients receiving maintenance therapy without corticosteroids, a minimization strategy using three-point pharmacokinetic sampling to reduce and maintain cyclosporine exposure to 50% of the usual levels is safe and reduces the risk of graft dysfunction.

Published
2010
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14. The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients

Author

Michaela Prokopova, Friedrich Thaiss, Andries J. Hoitsma, Bruno Hurault de Ligny, Anja Mühlfeld, Séverine Martin, Oliver Gross, Władysław Sułowicz, Annick Massart, Judith Racapé, Miguel Angel Gentil Govantes, A. Yussim, Frieder Keller, Umberto Maggiore, Matthew Howse, Gian Benedetto Piredda, Ricardo Lauzurica, Magali Giral, Luis Antonio Jiménez del Cerro, Marie-Christine Moal, Tomas Reischig, François Glowacki, Jean-François Subra, Bénédicte Janbon, Consuelo De Biase, María José Pérez-Sáez, Marian Klinger, Goce Spasovski, Philippe Gatault, Gaetano La Manna, David Berglund, Cem Tugmen, Giovanni M. Frascà, Uyen Huynh-Do, Christophe Legendre, Annaïck Pallier, Christopher Dudley, Mélanie Chesneau, Laura Braun, Daniel Abramowicz, Karine Hadaya, Christian Noel, Evangeline Pillebout, Carmen Díaz-Corte, Julio Pascual, Ondrej Viklicky, Florence Villemain, Luigi Biancone, Ana Ramírez Puga, Marije C. Baas, Alain Le Moine, Marc Abramowicz, Frederike J. Bemelman, Rainer Oberbauer, Jean-Paul Soulillou, Nurhan Seyahi, Jadranka Buturović Ponikvar, Johan W. de Fijter, Maarten Naesens, Vania Cuna, Klemens Budde, Serhan Tuglular, Pierrick Guerif, Angel Alonso Hernandez, Piero Stratta, Arnaud Garnier, Hulya Colak, K. Clemente, Sophie Brouard, Marc Hazzan, Søren Schwartz Sørensen, Giuseppe Orlando, Daniel Serón, Luboslav Beňa, Quirino Lai, Francesco Pisani, Aisling E. Courtney, Alexandre Dufay, Mehmet Sukru Sever, Thomas Wekerle, Hervé Le Monies De Sagazan, Hakim Mazouz, Aljoša Kandus, Maria Carmen Cantarell, André Gaasbeek, Massart, A, Pallier, A, Pascual, J, Viklicky, O, Budde, K, Spasovski, G, Klinger ,M, Sever, MS, Sørensen, SS, Hadaya, K, Oberbauer, R, Dudley, C, De Fijter, JW, Yussim, A, Hazzan, M, Wekerle, T, Berglund, D, De Biase, C, Pérez-Sáez, MJ, Mühlfeld, A, Orlando, G, Clemente, K, Lai, Q, Pisani, F, Kandus, A, Baas, M, Bemelman, F, Ponikvar, JB, Mazouz ,H, Stratta, P, Subra, JF, Villemain, F, Hoitsma, A, Braun, L, Cantarell, MC, Colak, H, Courtney, A, Frasca, GM, Howse, M, Naesens, M, Reischig, T, Serón, D, Seyahi, N, Tugmen, C, Alonso Hernandez, A, Beňa, L, Biancone, L, Cuna, V, Díaz-Corte, C, Dufay, A, Gaasbeek, A, Garnier, A, Gatault, P, Gentil Govantes, MA, Glowacki, F, Gross, O, Hurault de Ligny, B, Huynh-Do, U, Janbon, B, Jiménez Del Cerro, LA, Keller, F, La Manna, Gaetano, Lauzurica, R, Le Monies De Sagazan, H, Thaiss, F, Legendre, C, Martin, S, Moal, MC, Noël, C, Pillebout, E, Piredda, GB, Puga, AR, Sulowicz, W, Tuglular, S, Prokopova, M, Chesneau, M, Le Moine, A, Guérif, P, Soulillou, JP, Abramowicz, M, Giral, M, Racapé, J, Maggiore, U, Brouard, S, Abramowicz, D, AII - Amsterdam institute for Infection and Immunity, Nephrology, Renal Unit [Brussels, Belgium] (ULB), Université libre de Bruxelles (ULB)-CUB Hôpital Erasme [Bruxelles, Belgium], Medical Genetics Department [Brussels, Belgium], Université libre de Bruxelles (ULB), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Nephrology [Barcelona, Spain] (Hospital del Mar), Hospital del Mar [Barcelona, Spain], Department of Nephrology [Prague, Czech Republic] (Transplant Center), Institute for Clinical and Experimental Medicine (IKEM), Department of Nephrology [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Nephrology [Skopje, Macedonia], Ss. Cyril and Methodius University in Skopje, Nephrology and Transplantation Medicine [Wrocław, Poland], University of Wrocław [Poland] (UWr), Internal Medicine, Nephrology [Istanbul, Turkey], Istanbul School of Medicine [Istanbul, Turkey], Nephrology P [Copenhagen, Denmark], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, Nephrology and Transplantation [Geneva, Switzerland], Geneva University Hospitals - HUG [Switzerland], Department of Medicine III–Nephrology, Hypertension and Renal Transplantation [Linz, Austria], Krankenhaus Elisabethinen Linz [Linz, Austria], Richard Bright Renal Centre [Bristol, UK], Southmead Hospital [Bristol, UK]-North Bristol NHS Trust [Bristol, UK], Department of Nephrology [Leiden, The Netherlands], Leiden University Medical Center (LUMC), Department of Transplantation [Tel Aviv, Israël] (Rabin Medical Center), Rabin Medical Center [Tel Aviv, Israël]-Tel Aviv University Sackler School of Medicine [Tel Aviv, Israël], Département de Néphrologie [CHRU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Surgery [Vienna, Austria] (Section of Transplantation Immunology), Medizinische Universität Wien = Medical University of Vienna, Section of Clinical Immunology [Uppsala, Sweden] (Department of Immunology, Genetics and Pathology), Uppsala University, UOS Trapianti Rene Pancreas [Parma, Italy] (Centro Trapianti di Parma), Azienda Ospedaliero-Universitaria di Parma, Department of Nephrology [Aachen, Germany], University Hospital Aachen, Section of Transplantation [Winston-Salem, NC, USA] (Department of Surgery), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, U.O.C. Trapianti D’Organo [L’Aquila, Italy], Department of Nephrology [Ljubljana, Slovenia] (Renal Transplantation Centre Ljubljana), University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Kidney Diseases [Nijmegen, The Netherlands], Radboudumc Nijmegen [The Netherlands], Renal Transplant Unit [Amsterdam, The Netherlands] (Department of Nephrology), Academic Medical Center [Amsterdam, Netherlands], Unité de Transplantation Rénale et Pancréatique [CHU Sud, Amiens] (Service de Néphrologie), CHU Amiens-Picardie, Department of Translational Medicine [Novara, Italy], Amedeo Avogadro University of Eastern Piedmont, Service de Néphrologie-Dialyse-Transplantation [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), service de Néphrologie et Transplantation Rénale [CHU Strasbourg] (Hôpital de jour de Néphrologie), Centre Hospitalier Universitaire de Strasbourg (CHU de Strasbourg )-Nouvel Hôpital Civil - NHC [Strasbourg], Pediatric Nephrology [Barcelona, Spain] (Vall d’Hebron Hospital), Universitat Autònoma de Barcelona (UAB)-Vall d'Hebron University Hospital [Barcelona], Department of Nephrology [Izmir, Turkey], Tepecik Training and Research Hospital [Izmir, Turkey], Regional Nephrology Unit [Belfast, UK], Belfast City Hospital [Belfast, UK], Nefrologia, Dialisi e Trapianto di rene [Ancona, Italy], AO Torrette Umberto I [Ancona, Italy], Nephrology/Transplantation [Liverpool, UK], Royal Liverpool University Hospital [Liverpool, UK], Department of Nephrology and Renal Transplantation [Leuven, Belgium], University Hospitals Leuven [Leuven]-Catholic University Leuven, Nephrology Ward [Pilsen, Czech Republic] (Department of Internal Medicine), University Hospital Pilsen [Pilsen, Czech Republic], Istanbul University, Servicio de Nefrología, Hospital Universitario, A Coruña, Transplant Centre, University Hospital Louis Pasteur Kosice, University of Turin, St. Orsola University Hospital, University of Bologna, Hospital Universitario Central de Asturias (HUCA), Service Néphrologie [Roubaix], Hôpital Victor Provo, Leids Universitair Medisch Centrum [Leiden, The Netherlands], Néphrologie - Médecine Interne - Hypertension Pédiatrique, Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service Néphrologie - Immunoclinique [CHRU Tours], Hôpital Bretonneau, Hospital Universitario Virgen del Rocío [Sevilla], Service de Néphrologie et Transplantation rénale [CHRU-lille], University Medicine Göttingen, Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University of Bern [Bern, Switzerland] (University Hospital Bern ), Transplantation rénale [CHU Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Hospital General Universitario de Alicante, Universitätsklinikum Ulm - University Hospital of Ulm, Hospital Universitario Germans Trias I Pujol, University Hospital Hamburg-Eppendorf, Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hémodialyse et de Néphrologie [Libourne], Hôpital Robert Boulin, CHRU - Service de néphrologie, dialyse et transplantation rénale, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Néphrologie et transplantation [Hôpital Saint Louis - APHP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Kidney Transplant Az. Osp. G. Brotzu, Hospital Universitario Insular de Gran Canaria, University Hospital in Krakow, Marmara School of Medicine Hastanesi, Institute of Transplantation Urology and Nephrology [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, Research Center of Epidemiology, Biostatistics and Clinical Research, Nephrology-Renal Transplantation Department, Université libre de Bruxelles (ULB)-Universitair Ziekenhuis Antwerp, ERA-EDTA-DESCARTES working group, the Fonds Erasme (research grant), the Fonds Carine Vyghen, the Fonds Horlait-Dapsens, the RTRS Fondation de Coopération Scientifique CENTAURE and the IHUCesti project., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Ss. Cyril and Methodius University in Skopje (UKIM), Tel Aviv University (TAU)-Rabin Medical Center [Tel Aviv, Israël], Università degli studi di Torino = University of Turin (UNITO), University of Bologna/Università di Bologna, Service Néphrologie, médecine interne et hypertension pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CUB Hôpital Erasme [Bruxelles, Belgium]-Université libre de Bruxelles (ULB), and Hadaya, Karine

Subjects
0301 basic medicine, Nephrology, Graft Rejection, Male, medicine.medical_treatment, 030230 surgery, Kidney transplant, 0302 clinical medicine, Surveys and Questionnaires, Allograft survival, Kidney transplantation, ddc:616, Graft Survival/immunology, Survival Rate/trends, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Incidence, Graft Survival, Immunosuppression, operational tolerance, Transplantation, 3. Good health, Europe, Survival Rate, frequency, minimally immunosuppressed patients, Female, Hemodialysis, Graft Rejection/epidemiology/immunology/prevention & control, Homologous, Adult, medicine.medical_specialty, Ronyons -- Trasplantació -- Aspectes immunològics, Immunosuppression/methods, kidney transplantation, Europe/epidemiology, 03 medical and health sciences, Immune Tolerance/immunology, Internal medicine, medicine, Immune Tolerance, Humans, Transplantation, Homologous, Survival rate, Immunosuppression Therapy, graft survival, business.industry, medicine.disease, Kidney Transplantation, Transplant Recipients, Surgery, 030104 developmental biology, Operational tolerance, Human medicine, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background Kidney recipients maintaining a prolonged allograft survival in the absence of immunosuppressive drugs and without evidence of rejection are supposed to be exceptional. The ERA-EDTA-DESCARTES working group together with Nantes University launched a European-wide survey to identify new patients, describe them and estimate their frequency for the first time. Methods Seventeen coordinators distributed a questionnaire in 256 transplant centres and 28 countries in order to report as many operationally tolerant patients (TOL; defined as having a serum creatinine

Published
2015
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15. Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation

Author

Bruno Moulin, Joseph Rivalan, Matthias Büchler, Anne-Elisabeth Heng, Johnny Sayegh, Pierre-François Weestel, Bruno Hurault de Ligny, Renaud Snanoudj, Dominique Bertrand, Yvon Lebranchu, Antoine Thierry, Jean-Philippe Rerolle, Philippe Gatault, Bénédicte Sautenet, Charlotte Colosio, Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Universitaire de Reims (CHU Reims), Affectations Mineralisantes du Systeme Cardiovasculaire : Calcifications Arterielles et Valvulaires Aortiques, Université de Picardie Jules Verne (UPJV)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dyalise et transplantation, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Department of Kidney Transplantation CHU Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de néphrologie adultes [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Université Francois Rabelais [Tours], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de Néphrologie, Immunologie clinique, Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Service de Néphrologie et d’Immunologie Clinique, and Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Graft Rejection, Male, Time Factors, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Kaplan-Meier Estimate, 030230 surgery, 0302 clinical medicine, target of rapamycin-inhibitors, Cause of Death, Prospective Studies, Prospective cohort study, Kidney transplantation, immunosuppression, Statistics, Graft Survival, Immunosuppression, clinical trial, Middle Aged, 3. Good health, Survival Rate, surgical procedures, operative, Treatment Outcome, Cyclosporine, Female, Drug, Immunosuppressive Agents, medicine.drug, Adult, medicine.medical_specialty, Urology, Renal function, Risk Assessment, Drug Administration Schedule, Statistics, Nonparametric, Dose-Response Relationship, 03 medical and health sciences, medicine, Humans, Nonparametric, Survival rate, Immunosuppression Therapy, Sirolimus, Transplantation, Analysis of Variance, Dose-Response Relationship, Drug, business.industry, human leukocyte antigen-antibody posttransplantation, medicine.disease, Kidney Transplantation, Surgery, Regimen, business, Follow-Up Studies
Abstract

International audience; We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Published
2015
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16. Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients

Author

Bruno Moulin, Bruno Hurault de Ligny, Jacques Chanard, Corine Bernaud, Sylvie Lavaud, and Olivier Toupance

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Vasodilator Agents, Urology, Renal function, Hyperuricemia, Thiophenes, Kidney Function Tests, urologic and male genital diseases, Risk Assessment, Propanolamines, Double-Blind Method, Reference Values, Transplantation Immunology, Internal medicine, Cyclosporin a, medicine, Humans, Amlodipine, Transplantation, Kidney, business.industry, Graft Survival, Middle Aged, Kidney Transplantation, Treatment Outcome, Endocrinology, Blood pressure, medicine.anatomical_structure, Tertatolol, Nephrology, Renal blood flow, Renal physiology, Hypertension, Cyclosporine, Female, business, Immunosuppressive Agents, Follow-Up Studies, medicine.drug
Abstract

Background. Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5–10 mg/day) and the � adrenoceptor antagonist tertatolol (5–10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension. Methods. Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n ¼ 24) or tertatolol (n ¼ 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure. Results. Amlodipine significantly decreased serum uric acid levels from 483 ± 99 to 431 ± 110mmol/l (P < 0.001), while tertatolol significantly increased uric acid from 450 ± 98 to 476 ± 84mmol/l (P ¼ 0.006). Amlodipine also significantly increased glomerular filtration rate (P ¼ 0.0048) and the clearance rate of uric acid (P ¼ 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P ¼ 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated. Conclusions. Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients.

Published
2003
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17. Immunoprophylaxis with Basiliximab Compared with Antithymocyte Globulin in Renal Transplant Patients Receiving MMF-containing Triple Therapy

Author

Gérard Rifle, Yannick Le Meur, Bruno Moulin, Michel Guignard, O Reigneau, Patrick Le Pogamp, Matthias Büchler, Isabelle Etienne, Bruno Hurault de Ligny, Olivier Toupance, Yvon Lebranchu, Guy Touchard, and Frank Bridoux

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Time Factors, Basiliximab, Recombinant Fusion Proteins, medicine.medical_treatment, Urology, Mycophenolic acid, chemistry.chemical_compound, medicine, Humans, Immunology and Allergy, Pharmacology (medical), Kidney transplantation, Dialysis, Antilymphocyte Serum, Immunosuppression Therapy, Transplantation, Creatinine, Thymoglobulin, business.industry, Racial Groups, Antibodies, Monoclonal, Immunosuppression, Middle Aged, Mycophenolic Acid, medicine.disease, Kidney Transplantation, Tissue Donors, Surgery, chemistry, Tolerability, Cyclosporine, Kidney Failure, Chronic, Drug Therapy, Combination, Female, France, Safety, business, medicine.drug
Abstract

Acute graft rejection remains a major problem in renal transplant recipients, and there is no consensus on the optimal immunosuppressive strategy. Immunoprophylaxis with Thymoglobulin or basiliximab has significantly reduced the incidence of acute rejection episodes and graft loss following kidney transplantation. This open, randomized, multicenter study investigated the efficacy and tolerability of basiliximab (20mg day 0-day 4) plus early cyclosporine from day 0 (n = 50) compared with Thymoglobulin plus delayed cyclosporine (n = 50) in adult kidney transplant patients. In addition, all patients received steroids and mycophenolate mofetil (MMF) at standard doses from day 0. Patient and graft survival rates at 12 months were 98 and 94% in the basiliximab group, respectively, compared with 100 and 96% in the Thymoglobulin' group. The incidences of biopsy-confirmed acute rejection (8.0% in each group) and treatment failure (14% in the basiliximab group vs. 8% in the Thymoglobulin group) were comparable in the two groups. There was a non-significant tendency to more dialysis (14 vs. 6%), and fewer cytomegalovirus (CMV) infections (p = 0.005) in the basiliximab group, but the percentage of clinical CMV was not different between the two groups (6 vs. 12%). Both strategies give excellent results, despite the differences in patterns, in nonhyperimmunized patients receiving their first cadaveric renal allograft.

Published
2002
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18. Mutations of CEP83 Cause Infantile Nephronophthisis and Intellectual Disability

Author

Pauline Krug, Emilie Filhol, Robert Novo, Amandine Frigo, Olivier Alibeu, Daniela A. Braun, Ce´cile Masson, Karine Brochard, Lilya Belkacem, Alexandre Benmerah, Christine Pietrement, Marion Failler, Markus Schueler, Re´mi Salomon, Heon Yung Gee, Jonathan D. Porath, Bruno Hurault de Ligny, Joon Kim, Marie-Claire Gubler, Jan Halbritter, Edgar A. Otto, Kwangsic Joo, Friedhelm Hildebrandt, Hülya Kayserili, Corinne Antignac, and Sophie Saunier

Subjects
Central Nervous System, Male, Centriole, Biology, Ciliopathies, 03 medical and health sciences, Exon, 0302 clinical medicine, Nephronophthisis, Ciliogenesis, Report, Intellectual Disability, Genetics, medicine, Humans, Genetics(clinical), Cilia, Genetics (clinical), Exome sequencing, Alleles, 030304 developmental biology, Centrioles, 0303 health sciences, Cilium, Infant, Exons, Kidney Diseases, Cystic, Orofaciodigital Syndromes, medicine.disease, Ciliopathy, Child, Preschool, Mutation, Female, Microtubule-Associated Proteins, 030217 neurology & neurosurgery
Abstract

Ciliopathies are a group of hereditary disorders associated with defects in cilia structure and function. The distal appendages (DAPs) of centrioles are involved in the docking and anchoring of the mother centriole to the cellular membrane during ciliogenesis. The molecular composition of DAPs was recently elucidated and mutations in two genes encoding DAPs components (CEP164/NPHP15, SCLT1) have been associated with human ciliopathies, namely nephronophthisis and orofaciodigital syndrome. To identify additional DAP components defective in ciliopathies, we independently performed targeted exon sequencing of 1,221 genes associated with cilia and 5 known DAP protein-encoding genes in 1,255 individuals with a nephronophthisis-related ciliopathy. We thereby detected biallelic mutations in a key component of DAP-encoding gene, CEP83, in seven families. All affected individuals had early-onset nephronophthisis and four out of eight displayed learning disability and/or hydrocephalus. Fibroblasts and tubular renal cells from affected individuals showed an altered DAP composition and ciliary defects. In summary, we have identified mutations in CEP83, another DAP-component-encoding gene, as a cause of infantile nephronophthisis associated with central nervous system abnormalities in half of the individuals.

Published
2014

19. Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial

Author

Vincent Delwail, John Wijdenes, Dominique Debray, Marc Stern, Jean Marie Seigneurin, Anne Durandy, Christophe Duvoux, Véronique Leblond, Bruno Hurault De Ligny, Alain Fischer, Philippe Hubert, Sophie Paczesny, Antoine Achkar, Marc Bauwens, and Elie Haddad

Subjects
Adult, Male, Herpesvirus 4, Human, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Immunology, Antibodies, Viral, Biochemistry, Gastroenterology, Refractory, Internal medicine, medicine, Humans, Child, Immunodeficiency, B-Lymphocytes, Interleukin-6, business.industry, Antibodies, Monoclonal, Infant, Immunosuppression, Cell Biology, Hematology, Immunotherapy, Middle Aged, medicine.disease, Lymphoproliferative Disorders, Surgery, Clinical trial, C-Reactive Protein, Treatment Outcome, medicine.anatomical_structure, Therapeutic Equivalency, Child, Preschool, Tissue Transplantation, Monoclonal, Female, Bone marrow, Complication, business
Abstract

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

Published
2001
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20. Expansion of Cortical Interstitium Is Limited by Converting Enzyme Inhibition in Type 2 Diabetic Patients with Glomerulosclerosis

Author

Claire Barro, Rudolf W. Bilous, D. Cordonnier, Yves Reznic, Claire Maynard, Nicole Pinel, Serge Halimi, Bruno Hurault de Ligny, Philippe Zaoui, and Dominique Simon

Subjects
medicine.medical_specialty, business.industry, Renal glomerulus, Urology, Renal function, General Medicine, medicine.disease, Angiotensin II, Nephropathy, Diabetic nephropathy, Endocrinology, Nephrology, Internal medicine, ACE inhibitor, Perindopril, Medicine, business, medicine.drug, Kidney disease
Abstract

Renal interstitial expansion is now considered a useful marker of progression of several nephropathies. This study describes a multicenter, prospective, double-blind, pla- cebo-controlled, randomized trial of the effects of Perindopril (4 mg/d) on kidney structure and function over 2 yr in 26 type 2 diabetic patients with proteinuria ranging from 70 to 4210 mg/d and relatively preserved GFR (creatinine clearance .60 ml/min). All patients underwent baseline renal biopsy, but four (15%) were not randomized because of the presence of non- diabetic nephropathy. The remaining 22 were randomized (11 to Perindopril (PE), 11 to placebo (PO)), and 19 (9 PE, 10 PO) underwent follow-up biopsy at 2 yr. BP was controlled equally in both groups throughout. Proteinuria increased in PO patients (11562 mg/d) but declined in PE patients (2156 mg/d) (P , 0.05). Morphometric analysis was performed by light micros- copy using a Biocom computer. Over the 2 yr, mean cortical interstitial fractional volume identical at baseline increased significantly in PO patients (31.7 6 5.3 versus 40.2 6 11.1%; P 5 0.001) but was unchanged in PE patients (33.8 6 4.9 versus 34.7 6 6.6%; P 5 0.50). It is concluded that: (1) nondiabetic nephropathy is present in approximately 15% of albuminuric type 2 diabetic patients; and (2) Perindopril pre- vents interstitial expansion in hypertensive patients with biopsy-proven diabetic glomerulopathy. These results support a role of angiotensin II in the progression of interstitial changes in type 2 diabetic patients with nephropathy.

Published
1999
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21. Progression of pulse pressure in kidney recipients durably exposed to CsA is a risk factor for epithelial phenotypic changes: an ancillary study of the CONCEPT trial

Author

Yvon Lebranchu, Aude Servais, Eric Thervet, Sandrine Girardot-Seguin, Eric Rondeau, Yi-Chun Xu-Dubois, Bruno Hurault de Ligny, Patrick Le Pogamp, Maïté Jauréguy, Anne-Elisabeth Heng, Yann Le Meur, Vannary Meas-Yedid, Alexandre Hertig, Olivier Toupance, Guy Touchard, and Francis Bayle

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Time Factors, Population, Calcineurin Inhibitors, Urology, Blood Pressure, Kidney, Epithelium, Risk Factors, Post-hoc analysis, Biopsy, Medicine, Humans, Risk factor, education, Sirolimus, Transplantation, education.field_of_study, medicine.diagnostic_test, business.industry, Odds ratio, Middle Aged, Fibrosis, Kidney Transplantation, Pulse pressure, medicine.anatomical_structure, Phenotype, Immunology, Cyclosporine, Female, business, Immunosuppressive Agents, medicine.drug, Glomerular Filtration Rate
Abstract

Summary In this ancillary study of the CONCEPT trial, we studied the role of CsA withdrawal at 3 months (3M) post-transplant on the intensity of epithelial phenotypic changes (EPC, an early marker for kidney fibrogenesis) on the 12M surveillance biopsy. Although conversion from CsA to sirolimus (SRL) at 3M was reported to have improved mean graft function at 12M, it did not reduce the score of EPC (1.73 ± 1.15 in the SRL group vs. 1.87 ± 1 in the CsA group, P = 0.61). Acute rejection, which had occurred twice more frequently in SRL-converted patients included here, was associated with 12M EPC. Interestingly, we observed that the patients durably exposed to CsA and who developed 12M EPC had a significant progression of blood pulse pressure (pp) from 1 to 6M post-transplantation (Δpp = +12.3 mmHg, P = 0.0035). Pulse pressure at 4, 6, and 9M and pp progression from 1 to 6M were significantly associated with the development of EPC at 12M in renal grafts. Logistic regression analysis revealed that a high 6M pp (≥60 mmHg) was an independent risk factor for 12M EPC with an odds ratio of 2.25 per additional 10 mmHg pp (95%CI: 1.14–4.4, P = 0.02) after adjustment with recipient's and donor's age, acute rejection incidence and immunosuppressive regimen. A post hoc analysis of the data collected in the whole population CONCEPT study revealed that pp was significantly higher at 6 months in patients maintained on CsA and that at this time point pp correlated negatively with GFR at 1 year.

Published
2013

22. MP739TRANSPLANT RENAL ARTERY STENOSIS : A CASE SERIES

Author

Christiane Mousson, Cécile Vigneau, Marie Frimat, Michel Godin, Pierre Merville, Mohammad Kilani, Marc Hazzan, Christian Noel, Sophie Caillard-Ohlmann, Dany Anglicheau, Gabriel Choukroun, François Glowacki, Bruno Hurault de Ligny, Laurent Lemaitre, and Anne-Sophie Vasseur

Subjects
Transplantation, Series (stratigraphy), medicine.medical_specialty, business.industry, 030232 urology & nephrology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Nephrology, Internal medicine, medicine, Cardiology, Transplant renal artery stenosis, business
Published
2016
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23. A clinical scoring system highly predictive of long-term kidney graft survival

Author

Georges Mourad, Christophe Legendre, François Bayle, Magali Giral, Nassim Kamar, Pascal Daguin, Marc Ladrière, Michèle Kessler, Mathias Büchler, Carole Meier, Jean-Paul Soulillou, Henri Kreis, Jean Pierre Daures, Ahmed Akl, Valérie Garrigue, Lionel Rostaing, Yohann Foucher, and Bruno Hurault de Ligny

Subjects
Nephrology, Adult, Graft Rejection, Male, medicine.medical_specialty, Scoring system, Composite score, Adolescent, Urinary system, chemistry.chemical_compound, Young Adult, Predictive Value of Tests, Risk Factors, Internal medicine, medicine, Humans, Child, Aged, Proportional Hazards Models, Aged, 80 and over, Kidney, Creatinine, business.industry, Graft Survival, prediction models, Infant, Reproducibility of Results, surrogate end points, Middle Aged, Prognosis, Kidney Transplantation, Surgery, Transplantation, medicine.anatomical_structure, surgical procedures, operative, chemistry, ROC Curve, Child, Preschool, Graft survival, Female, business, Algorithms, transplantation, Follow-Up Studies
Abstract

Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Donnees Informatisees et VAlidees en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre- and post-transplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver–operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.

Published
2010

24. Comparative effects of sirolimus and cyclosporin on conduit arteries endothelial function in kidney recipients

Author

Robinson, Joannides, Isabelle, Etienne, Michele, Iacob, Bruno, Hurault de Ligny, Stephane, Barbier, Jeremy, Bellien, Yvon, Lebranchu, Christian, Thuillez, and Michel, Godin

Subjects
Adult, Male, Sirolimus, Time Factors, Blood Pressure, Arteries, Middle Aged, Kidney, Kidney Transplantation, Ischemia, Cyclosporine, Humans, Female, Endothelium, Vascular, Prospective Studies, Immunosuppressive Agents, Glomerular Filtration Rate
Abstract

This study attempted to establish whether a calcineurin inhibitor (CNI)-free immunosuppressant regimen based on sirolimus (SRL) is associated with a preservation of conduit arteries endothelial function in kidney recipients or not. Twenty-nine kidney recipients were randomized to receive since transplantation SRL (n=15) or cyclosporin A (CsA, n=14) associated with mycophenolate mofetil (MMF) and steroids (6months) in a parallel prospective study. Systolic, diastolic blood pressures, glomerular filtration rate (GFR) and radial artery flow-mediated dilatation (FMD) induced by postischaemic hyperaemia were assessed in a blind manner at one (M1) and 7months (M7) after transplantation. Endothelium-independent dilatation was assessed by glyceryl trinitrate spray. There was no difference between the groups for all vascular parameters at M1. At M7, systolic blood pressure was lower (SRL: 119±3 vs. CsA: 138±4mmHg, P0.05) and FMD was higher in SRL compared with CsA (SRL: 13.1±0.9 vs. CsA: 9.9±0.9%, P0.05) without any difference for hyperaemia, endothelium-independent dilatation and GFR (SRL: 66.7±1.05 vs. CsA: 67.5±1.22ml/min). Our results demonstrate that a CNI-free regimen based on SRL and MMF prevents conduit artery endothelial dysfunction compared with CsA and MMF in kidney recipients suggesting a beneficial arterial wall effect that may also contribute to the decrease in systolic blood pressure.

Published
2010

25. Contents, Vol. 58, 1991

Author

Z.H. Endre, Lawrence S. Milner, F. Lemercier, Susanne Horner, Yuji Nagura, P. Saiag, Kazuro Kanatsu, G.A. Balderson, Nachman Brautbar, Takahiko Ono, Franz Fazekas, Atul T. Roy, M.C. de Vernejoul, Tateki Kitaoka, Ove Noren, Geoffrey H. Cope, Xi-Xiong Kang, Michèle Kessler, Batya Kristal, S.L. Lynch, Toshio Doi, Wolfgang Freidl, M.H. Gault, D.H.G. Crawford, Hans Sjöström, M. Potiron-Josse, Masami Kozaki, R. Korte, Jörg H. Horina, Chika Onoe, Yasuhiko Ito, H. Longerich, Kazutomo Ujiie, Mark T. Houser, J.D. Ginet, Helmut Pogglitsch, Nicholas D. Slater, O. Jovanović, A. Quoidbach, Masaharu Yoshida, S.J. Fleming, C.G.H. Maidment, P.C.K. Chan, H. Demol, I. Lubrich-Birkner, H.B. Steinhauer, Monique Elseviers, Luiz C. Cintra, Tamar Shkolnik, M. Kostić, Marc E. De Broe, P. Schollmeyer, Frank L. Van de Vyver, Paulo Sérgio Medeiros dos Santos, Y. Pirson, Takashi Suzuki, Guy D. Nuyts, Eri Muso, Norio Kaji, L. Longerich, Tadao Akizawa, Kazuyoshi Okada, Hiroyuki Nagai, Franz Payer, Osnat Steinberger, K.W. Chan, Atsushi Fukatsu, Hanns M. Winkler, Ronny A. Daelemans, Michinobu Hatano, D. Le Carrer, P. Galle, P. Bindi, Hirofumi Tamai, Tohru Tamaki, Kazuhiro Nishikawa, Bruno Hurault de Ligny, Wahei Matsukawa, Patrick C. D'Haese, Ab. Akosa, Guenter J. Krejs, Heinz Valetitsch, T.M. Chan, Andrew T. Raftery, Niembro De Rasche, M.A. Rengel, Mamoru Maejima, Chuichi Kawai, R. Khayat, Martin Magnusson, Anna Galar, Eriko Kinugasa, B. Winterberg, Uri Shasha, Roberto Silva Costa, Shaul M. Shasha, Etsuo Sakurai, Michael Slater, P. Gris, Futoshi Yoshida, Gomez Campdera, Tatsuto Kimachi, M. Popović-Rolović, Akira Owada, Torsten Denneberg, Nils-Georg Asp, Marie C. Béné, Kimio Tomita, H.P. Bertram, Noriaki Matsui, Hidekazu Shigematsu, Agenor Spallini Ferraz, Gilbert C. Faure, Shozo Koshikawa, Tadao Tamura, Sverker Eneström, J.-P. Vaerman, Maria Walczuk, Stanislaw Jankowski, David B. N. Lee, V.L.M. Esnault, D. Popović, Toshihiko Hirano, Philippe G. Jorens, F. Anaya, Susumu Takahashi, A. Testa, Kryspina Grzybek-Hryncewicz, Satoshi Sekiyama, Haruyoshi Yoshida, Mitsuru Yanai, A. Antić-Peco, Seiichi Matsuo, J. Hamels, Miriam Barzilai, B. Viron, I.K.P. Cheng, Fumiaki Marumo, Vanda Jorgetti, Márcio Dantas, F. Valderrabano, R.A. Axelsen, J. Guenel, Kitaro Oka, A. Galan, A. Sherif, Kenichi Sekita, I. Keck, Kurt Niederkorn, and N.R. Robles

Subjects
Traditional medicine, business.industry, Medicine, business
Published
1991
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26. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

Author

Veronique Frémeaux-Bacchi, Elizabeth C. Miller, M. Kathryn Liszewski, Lisa Strain, Jacques Blouin, Alison L. Brown, Nadeem Moghal, Bernard S. Kaplan, Robert A. Weiss, Karl Lhotta, Gaurav Kapur, Tej Mattoo, Hubert Nivet, William Wong, Sophie Gie, Bruno Hurault de Ligny, Michel Fischbach, Ritu Gupta, Richard Hauhart, Vincent Meunier, Chantal Loirat, Marie-Agnès Dragon-Durey, Wolf H. Fridman, Bert J. C. Janssen, Timothy H. J. Goodship, and John P. Atkinson

Subjects
Adult, Heterozygote, Adolescent, Immunology, DNA Mutational Analysis, Mutation, Missense, Infant, Cell Biology, Hematology, Complement C3, urologic and male genital diseases, Biochemistry, Hemostasis, Thrombosis, and Vascular Biology, Young Adult, Codon, Nonsense, hemic and lymphatic diseases, Child, Preschool, Hemolytic-Uremic Syndrome, Mutation, Humans, Genetic Predisposition to Disease, Child
Abstract

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.

Published
2008

27. Is rapid initiation of peritoneal dialysis feasible in unplanned dialysis patients? A single-centre experience

Author

Thierry Lobbedez, Angélique Lecouf, Maxence Ficheux, Jean-Philippe Ryckelynck, P. Henri, and Bruno Hurault de Ligny

Subjects
Nephrology, Male, medicine.medical_specialty, medicine.medical_treatment, Peritoneal dialysis, Catheters, Indwelling, Renal Dialysis, Internal medicine, medicine, Humans, Renal replacement therapy, Prospective Studies, Dialysis, Aged, Transplantation, Catheter insertion, business.industry, Middle Aged, medicine.disease, Surgery, Catheter, Kidney Failure, Chronic, Female, Hemodialysis, business, Peritoneal Dialysis, Kidney disease
Abstract

Starting dialysis in an unplanned manner is a frequent situation in a dialysis centre even for patients with a regular nephrology follow-up. For no clear reason, chronic haemodialysis (HD) is more frequently used than peritoneal dialysis for unplanned dialysis patients.The purpose of this study was to evaluate the results of a dialysis policy dedicated to unplanned dialysis patients. The aim of this policy was to increase the use of peritoneal dialysis (PD) in an attempt to reduce the need for tunnelled catheter.One hundred seventy-one patients from a single centre, who started dialysis between 1 January 2004 and 31 December 2006, were prospectively followed until 31 December 2006. Unplanned dialysis patients were defined as patients entering in dialysis with no vascular access or peritoneal dialysis catheter. PD was presented as a modality of choice for renal replacement therapy to avoid the need for a tunnelled HD catheter.There were 60 unplanned dialysis patients during the study period. Among these patients, 34 agreed to be treated by PD. Compared with unplanned peritoneal dialysis patients, unplanned haemodialysis patients had a greater modified Charlson's comorbidity index (5.9 +/- 2.4 versus 4.4 +/- 1.9, P0.05). The mean duration of the temporary catheter period was 32 +/- 29 days (median: 24 days) for haemodialysis patients compared with 26 +/- 21 days (median: 25 days) for peritoneal dialysis patients (P = NS). The initial hospitalization duration was similar in haemodialysis patients and peritoneal dialysis patients (24 +/- 28 versus 30 +/- 33 days; median value: 17 versus 20 days, P = NS). PD was started 8.6 +/- 10 days (median: 4 days) after catheter insertion. A tunnelled catheter was used only in three patients until peritoneal dialysis was initiated. Acute automated peritoneal dialysis was used in 19 patients. Among 26 haemodialysis patients, 23 were dialyzed through a tunnelled catheter. Of these 23 patients, 15 were successfully converted to fistula. Median time for fistula creation was 2.6 months after dialysis initiation; median time for fistula utilization was 4.4 months. Actuarial patients survival at 1 year was 79% on haemodialysis compared with 83% on peritoneal dialysis (P = NS). After adjustment of the initial modified Charlson's comorbidity index, dialysis modality had no impact on patient's survival. There was no significant difference between haemodialysis patients and peritoneal dialysis patients regarding survival free of re-hospitalization. Actuarial survival free of peritonitis was 73% at 6 months and 58% at 1 year.Peritoneal dialysis is a safe and efficient alternative to haemodialysis for unplanned dialysis patients. Peritoneal dialysis offers the advantage of reducing the need for tunnelled catheter in unplanned dialysis patients.

Published
2008

28. Impact of graft mass on the clinical outcome of kidney transplants

Author

Jean Michel Nguyen, Magali Giral, François Bayle, Pascal Daguin, Yohann Foucher, Georges Karam, Jean-Paul Soulillou, Carole Meyer, M. Kessler, Mattias Buchler, Bruno Hurault de Ligny, and Marie Laure Martin

Subjects
Nephrology, Adult, Male, medicine.medical_specialty, Adolescent, Mass reduction, Urinary system, Cadaver kidney, Kidney, Risk Factors, Internal medicine, medicine, Cadaver, Humans, Prospective Studies, Aged, Proportional Hazards Models, urogenital system, business.industry, Graft Survival, General Medicine, Nephrons, Organ Size, Middle Aged, Kidney Transplantation, Tissue Donors, Large cohort, Surgery, Transplantation, surgical procedures, operative, medicine.anatomical_structure, Kidney Failure, Chronic, Female, business
Abstract

The effect of nephronic mass reduction of kidney transplants has not been analyzed specifically in a large cohort. Transplant injuries in cadaver kidney graft may have led to an underestimation of the magnitude of this factor. The aim of this study was to analyze the consequences of kidney mass reduction on transplantation outcome. The weights of 1142 kidney grafts were collected prospectively immediately before grafting. Donors and recipients15 yr of age, simultaneous kidney/pancreas grafts, and technical failures before day 7 were excluded from the analysis. The analysis was performed on Cockroft-calculated creatinine clearance and proteinuria in 964 patients for whom all of the necessary information was available. This study reports that the smallest kidneys transplanted into the largest recipients (donor kidney weight/recipient body weight [DKW/RBW]2 g/kg, n = 88) increased their clearance by 2.38 ml/min every month for 6 mo (P0.0001) and by 0.27 ml/min thereafter (P0.0001). Conversely, creatinine clearance did not change for the largest kidneys transplanted into the smallest recipients (DKW/RBW ratios/=4 g/kg). Next, using a Cox model analysis, it was shown that the risk of having a proteinuria0.5 g/kg was significantly increased for the low DKW/RBW ratios2 g/kg with 50% of patients having a proteinuria, compared with DKW/RBW ratios/=4 g/kg (P0.001). In cadaver transplant recipients, graft mass has a rapid impact on graft filtration rate and proteinuria. Avoiding major kidney/recipient inadequacy should have a significant influence on long-term transplant function.

Published
2004

29. Polymorphism of angiotensin converting enzyme, angiotensinogen, and angiotensin II type 1 receptor genes and end-stage renal failure in IgA nephropathy: IGARAS--a study of 274 Men

Author

Marie-Noëlle Maghakian, Bruno Hurault de Ligny, Christophe Philippe, Luc Frimat, Philippe Jonveaux, Francis Guillemin, and Michèle Kessler

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Genotype, Angiotensinogen, Peptidyl-Dipeptidase A, Gastroenterology, Receptor, Angiotensin, Type 2, Receptor, Angiotensin, Type 1, Nephropathy, chemistry.chemical_compound, Predictive Value of Tests, Internal medicine, Medicine, Humans, Longitudinal Studies, Child, Aged, Retrospective Studies, Aged, 80 and over, Creatinine, Proteinuria, Polymorphism, Genetic, Receptors, Angiotensin, medicine.diagnostic_test, biology, business.industry, Angiotensin-converting enzyme, Glomerulonephritis, IGA, General Medicine, Middle Aged, medicine.disease, Angiotensin II, Survival Analysis, Endocrinology, chemistry, Nephrology, biology.protein, Kidney Failure, Chronic, Gene polymorphism, Renal biopsy, medicine.symptom, business, Kidney disease
Abstract

The impact of renin-angiotensin system (RAS) gene polymorphism on the prognosis of IgA nephropathy (IgAN) is still debated. A longitudinal study of renal prognosis in patients with IgAN was conducted to search retrospectively for a genotype-phenotype association between RAS polymorphisms and end-stage renal failure (ESRF). A classification based on serum creatinine (S(cr)) and 24-h proteinuria (24-P) measured at the time of renal biopsy was used to estimate the risk of ESRF in IgAN: stage 1 (S(cr)/= 150 micromol/L and 24-P1 g), stage 2 (S(cr)150 micromol/L and 24-P1 g or S(cr)or = 150 micromol/L and 24-Por = 1 g), stage 3 (S(cr)150 micromol/L and 24-Por = 1 g). Deletion/insertion polymorphism (D/I) of the angiotensin I converting enzyme gene, M235T polymorphism (T/M) of the angiotensinogen gene and A1166C polymorphism (C/A) of the angiotensin II type 1 receptor gene were determined in 274 Caucasian men with biopsy-proven IgAN (n = 86, 112, and 76 in stages 1, 2, and 3, respectively). Mean global follow-up was 6 +/- 5 yr after renal biopsy. For stages 1, 2, and 3, ESRF developed in 7 (8. 1%), 39 (34.8%), and 49 (64.4%) cases (P:0.0001), 11.7 +/- 4, 5.4 +/- 4, and 2 +/- 2 yr, respectively, after renal biopsy (P:0.001). The distributions of the three genotypes into the three stages were similar. Different distributions were observed when patients were grouped by stage and genotype: ID+DD: 72% in stage 1 versus 84.6% in stages 2 + 3 (P: = 0.02; kappa = 0.14); MT+TT: 66.2% in stages 1 + 2 versus 78.9% in stage 3 (P: = 0.04; kappa = 0.09); and AA+AC: 89.9% in stages 1 + 2 versus 97.4% in stage 3 (P: = 0.04; kappa = -0.1). However, with the use of the Cox proportional hazard model, none of the three genotypes was found to have predictive value for renal survival. Compared with S(cr) and 24-P, genotypes DD, TT, and AA are unlikely to serve as clinically useful predictors of ESRF in IgAN.

Published
2000

30. Sirolimus tolerability in a kidney transplant recipient with acute intermittent porphyria

Author

Wael El Haggan, Jean-Philippe Ryckelynck, Thierry Lobbedez, and Bruno Hurault de Ligny

Subjects
Transplantation, medicine.medical_specialty, business.industry, medicine.disease, Gastroenterology, Kidney transplant recipient, Tolerability, Nephrology, Sirolimus, Internal medicine, medicine, business, Kidney transplantation, medicine.drug, Acute intermittent porphyria
Published
2002
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31. Subject Index, Vol. 58, 1991

Author

M.C. de Vernejoul, S.J. Fleming, Eriko Kinugasa, J.-P. Vaerman, Franz Fazekas, Susanne Horner, Tateki Kitaoka, Yuji Nagura, J. Hamels, Franz Payer, M.A. Rengel, Xi-Xiong Kang, Roberto Silva Costa, Atul T. Roy, Miriam Barzilai, Kazuhiro Nishikawa, Atsushi Fukatsu, T.M. Chan, Hanns M. Winkler, Fumiaki Marumo, M. Popović-Rolović, Hiroyuki Nagai, David B. N. Lee, B. Winterberg, Vanda Jorgetti, Osnat Steinberger, Márcio Dantas, Lawrence S. Milner, Hidekazu Shigematsu, G.A. Balderson, A. Quoidbach, D. Popović, Gomez Campdera, F. Valderrabano, A. Sherif, F. Lemercier, Norio Kaji, Z.H. Endre, Tatsuto Kimachi, Kazutomo Ujiie, Helmut Pogglitsch, Michinobu Hatano, R. Korte, P. Bindi, Kazuro Kanatsu, K.W. Chan, Bruno Hurault de Ligny, Toshihiko Hirano, Chika Onoe, Yasuhiko Ito, J. Guenel, Tadao Tamura, Sverker Eneström, Nachman Brautbar, Philippe G. Jorens, Maria Walczuk, Monique Elseviers, Wahei Matsukawa, C.G.H. Maidment, A. Galan, O. Jovanović, Hans Sjöström, P. Schollmeyer, Tohru Tamaki, A. Antić-Peco, Tadao Akizawa, Kazuyoshi Okada, Paulo Sérgio Medeiros dos Santos, Kitaro Oka, Guy D. Nuyts, Eri Muso, Mamoru Maejima, M. Potiron-Josse, H. Demol, Gilbert C. Faure, Chuichi Kawai, Uri Shasha, Haruyoshi Yoshida, Takahiko Ono, Kryspina Grzybek-Hryncewicz, Marc E. De Broe, D. Le Carrer, I. Keck, Torsten Denneberg, Geoffrey H. Cope, Masami Kozaki, Kurt Niederkorn, F. Anaya, Shozo Koshikawa, Nils-Georg Asp, Marie C. Béné, Martin Magnusson, Anna Galar, Susumu Takahashi, A. Testa, Kimio Tomita, Etsuo Sakurai, Mitsuru Yanai, Niembro De Rasche, N.R. Robles, Kenichi Sekita, R. Khayat, Shaul M. Shasha, Futoshi Yoshida, H. Longerich, Takashi Suzuki, Stanislaw Jankowski, V.L.M. Esnault, B. Viron, I.K.P. Cheng, P. Saiag, R.A. Axelsen, Ronny A. Daelemans, S.L. Lynch, D.H.G. Crawford, Mark T. Houser, Patrick C. D'Haese, H.B. Steinhauer, Michèle Kessler, Andrew T. Raftery, Luiz C. Cintra, Tamar Shkolnik, Y. Pirson, Jörg H. Horina, Satoshi Sekiyama, Batya Kristal, Nicholas D. Slater, Toshio Doi, Wolfgang Freidl, M.H. Gault, Masaharu Yoshida, Heinz Valetitsch, P.C.K. Chan, J.D. Ginet, M. Kostić, Frank L. Van de Vyver, Ove Noren, L. Longerich, I. Lubrich-Birkner, P. Galle, Hirofumi Tamai, Ab. Akosa, Guenter J. Krejs, Michael Slater, P. Gris, Akira Owada, H.P. Bertram, Noriaki Matsui, Agenor Spallini Ferraz, and Seiichi Matsuo

Subjects
Index (economics), business.industry, Statistics, Medicine, Subject (documents), business
Published
1991
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32. Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients.

Author

Jacques Chanard, Olivier Toupance, Sylvie Lavaud, Bruno Hurault de Ligny, Corine Bernaud, and Bruno Moulin

Abstract

Background. Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5–10 mg/day) and the β-adrenoceptor antagonist tertatolol (5–10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension.Methods. Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure.Results. Amlodipine significantly decreased serum uric acid levels from 483 ± 99 to 431 ± 110 μmol/l (P < 0.001), while tertatolol significantly increased uric acid from 450 ± 98 to 476 ±84 μmol/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P = 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P = 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated.Conclusions. Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients. [ABSTRACT FROM AUTHOR]

Published
2003
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