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1. Chronic Hepatitis C Virus Infection After Kidney Transplantation With or Without Direct-Acting Antivirals in a Real-Life Setting: A French Multicenter Experience

Author

Nicolas Bouvier, Yannick Le Meur, Cyril Garrouste, Dominique Bertrand, Johnny Sayegh, Eloi Chevallier, Matthias Büchler, Sophie Caillard, Joseph Rivalan, Antoine Thierry, Lionel Rostaing, Philippe Gatault, Charlotte Colosio, Jean-Philippe Rerolle, Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Centre Hospitalier Universitaire [Grenoble] (CHU), Laboratory of Immunology, CHRU de Tours, Tours, France, Service de néphrologie et hémodialyse [CHU de Strasbourg], CHU Strasbourg, 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), Department of Nephrology, Reims University Hospital, Reims, France, Centre Hospitalier Universitaire de Rennes (CHU Rennes), Département de Néphrologie-Dialyse-Transplantation [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Néphrologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), 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), Département de Néphrologie [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de Néphrologie [Clermont-Ferrand], CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, 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), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble

Subjects
Adult, Male, Ledipasvir, medicine.medical_specialty, Pyrrolidines, Daclatasvir, Sustained Virologic Response, Sofosbuvir, 030232 urology & nephrology, Antiviral Agents, Gastroenterology, Group A, Virus, Group B, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Humans, Medicine, Kidney transplantation, Retrospective Studies, Fluorenes, Transplantation, business.industry, Imidazoles, virus diseases, Valine, Hepatitis C, Chronic, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, Treatment Outcome, chemistry, [SDV.IMM]Life Sciences [q-bio]/Immunology, Benzimidazoles, Female, 030211 gastroenterology & hepatology, Surgery, Carbamates, France, business, Viral hepatitis, medicine.drug
Abstract

Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.

Published
2020
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2. Early Prediction of Graft Outcomes After Kidney Transplantation From Donors After Circulatory Death: Biomarkers and Transplantation Characteristics

Author

Paolo Malvezzi, Rachel Tetaz, Candice Trocme, Diane Giovannini, Xavier Moreau-Gaudry, Bénédicte Janbon, Lionel Rostaing, Anne-Sophie Truche, Sabrina Vergnaud, Service de néphrologie, dialyse, aphérèses et transplantation, and Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble

Subjects
Adult, Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Urinary system, Population, 030232 urology & nephrology, Urology, Delayed Graft Function, Renal function, 030230 surgery, 03 medical and health sciences, 0302 clinical medicine, Lipocalin-2, Risk Factors, Acetylglucosaminidase, medicine, Clinical endpoint, Humans, education, Kidney transplantation, Transplantation, education.field_of_study, Kidney, L-Lactate Dehydrogenase, business.industry, Middle Aged, Prognosis, medicine.disease, Kidney Transplantation, Tissue Donors, Confidence interval, 3. Good health, Perfusion, medicine.anatomical_structure, ROC Curve, Creatinine, Female, Surgery, business, Biomarkers
Abstract

Background This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs). Methods Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3. The primary outcome was the occurrence of delayed graft function (DGF). Descriptive and receiver operating characteristic analyses were performed. Results Forty-one patients were included in the analysis: 15 (36.59%) DCD KTs (9 of which suffered from DGF) and 26 (63.41%) living donor KTs. For the primary endpoint, neutrophil gelatinase-associated lipocalin, N-acetyl-beta-D-glucosaminidase, urinary tubular injury biomarker-to-creatinine ratio, and LDH areas under the curve were 1 and 0.96 (95% confidence interval: 0.84-1.0), 1 and 0.92 (95% confidence interval: 0.73-1.0), respectively. Among the transplant characteristics, only the 30-minute resistive index on the perfusion machine was significantly higher in DCD KTs with DGF vs those without DGF (0.26 mm Hg/mL/min [0.20; 0.32] vs 0.14 mm Hg/mL/min [0.12; 0.16], P = .05). Median 3-month creatinine clearance among DGF DCD KTs was 49 mL/min/1.73 m2 [IQR: 42; 65] and 65 mL/min/1.73 m2 [IQR: 62; 66] among DCD KTs without DGF (P = .22). Conclusion In the DCD KT population, clinical and biological markers were identified that provided predictive tools for DGF. Thus, systematic measurement of these biomarkers, particularly LDH, could improve the management of kidney graft recipients’ immunosuppressive therapy.

Published
2019
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3. Use of rituximab as an induction therapy in anti-glomerular basement-membrane disease

Author

Lionel Rostaing, Giovanna Clavarino, M. Heitz, N. Pinel, P.L. Carron, Thomas Jouve, F. Guebre-Egziabher, Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Barrière Naturelle et Infectiosité (TIMC-IMAG-BNI), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [CHU Grenoble], CHU de Grenoble, Département d'anatomie et cythologie pathologique, and CHU Grenoble-Hôpital Michallon

Subjects
Nephrology, Adult, Male, medicine.medical_specialty, Cyclophosphamide, Adolescent, Anti-Glomerular Basement Membrane Disease, medicine.medical_treatment, 030232 urology & nephrology, Disease, urologic and male genital diseases, lcsh:RC870-923, Induction therapy, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Antineoplastic Agents, Immunological, Renal Dialysis, Internal medicine, Anti-glomerular basement-membrane disease, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Dialysis, Aged, Retrospective Studies, Aged, 80 and over, Kidney, Plasma Exchange, urogenital system, business.industry, fungi, Remission Induction, food and beverages, Goodpasture disease, Middle Aged, lcsh:Diseases of the genitourinary system. Urology, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Rituximab, Female, business, medicine.drug, Follow-Up Studies
Abstract

Background Anti-glomerular basement-membrane (anti-GBM) disease (or Goodpasture disease) is characterized by severe kidney and lung involvement. Prognoses have improved with treatments that combine plasma exchange and immunosuppressive drugs. However, patients with severe renal involvement can have poor renal outcomes and cyclophosphamide can cause significant complications. Anti-GBM antibodies have a direct pathogenic effect on the disease: thus, therapeutics that can decrease their production, such as rituximab, could be a good alternative. Methods The medical files of five patients that had received rituximab as a first-line therapy (instead of cyclophosphamide), plus plasma exchange and steroids, were reviewed. All patients had severe disease manifestations. Results Four patients required dialysis at diagnosis and remained dialysis-dependent over the mean follow-up of 15 months. Three patients had pulmonary involvement, but recovered even though mechanical ventilation was required. Anti-GBM antibodies became rapidly undetectable in all patients. One infectious and two hematological complications were observed. Conclusions We report the outcomes of five patients with Goodpasture disease and treated with rituximab as a first-line treatment. This strategy was effective at treating pulmonary manifestations and was associated with a good biological response with no major serious adverse events. However, renal outcomes were not significantly improved.

Published
2018
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4. Effects of immunoadsorption combined with membrane filtration on complement markers – results of a randomized, controlled, crossover study

Author

F. Defendi, Chantal Dumestre-Pérard, Georg A. Böhmig, Lionel Rostaing, Farsad Eskandary, Paolo Malvezzi, Jean-Yves Cesbron, LABORATOIRE D'IMMUNOLOGIE, Centre Hospitalier Universitaire [Grenoble] (CHU), Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, division of nephrology and dialysis, Barrière Naturelle et Infectiosité (TIMC-IMAG-BNI), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Adult, Male, kidney transplantation, chemical and pharmacologic phenomena, membrane filtration, 030230 surgery, Pharmacology, ABO Blood-Group System, 03 medical and health sciences, 0302 clinical medicine, ABO blood group system, Medicine, Humans, complement, mannose-binding lectin, Immunoadsorption, Complement Activation, Kidney transplantation, Mannan-binding lectin, Transplantation, Kidney, Cross-Over Studies, business.industry, Membranes, Artificial, Complement System Proteins, Middle Aged, medicine.disease, 3. Good health, Complement system, properdin, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunoglobulin M, Blood Group Incompatibility, Blood Component Removal, Properdin, Kidney Failure, Chronic, 030211 gastroenterology & hepatology, Female, Adsorption, business, immunoadsorption
Abstract

International audience; The complement system has been implicated in several kidney diseases, such as antibody-mediated rejection after kidney transplantation. Antibody-depletion techniques allow successful ABO- and/or HLA-incompatible transplantation. Considering the IgG removal, the use of semi-selective immunoadsorption (IA) has been advocated. However, because of results on incomplete IgM depletion, the adjunctive use of membrane filtration (MF) has been proposed to enhance the removal of macromolecules and to interfere with complement activation. This secondary endpoint analysis of a recently published randomized, controlled, cross-over trial was designed to investigate the effect of combined treatment IA + MF compared to IA alone on complement depletion. Two treatment sequences, a single session of IA + MF followed by IA (and vice versa), were analyzed with regard to C5b-9, properdin, and mannose-binding lectin (MBL) levels. Neither IA alone nor IA + MF provoked complement activation as demonstrated by stable low levels of C5b-9 after the procedure as compared to the previous. The combined treatment substantially lowered properdin (77% vs. 26% reduction, P

Published
2019
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5. Extracorporeal photopheresis for the treatment of graft rejection in 33 adult kidney transplant recipients

Author

Carole Philipponnet, Aurélien Tiple, Cyril Garrouste, Bruno Pereira, Philippe Grimbert, Etienne Merlin, Mathilde Tamain, George Kosmadakis, Mathias Büchler, Arnaud Lionet, Jean-François Augusto, Johnny Sayegh, Marc Hazzan, Anne-Elisabeth Heng, Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université d'Angers (UA), Service de Néphrologie et Transplantation rénale [CHRU-lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lille, Université de Tours (UT), Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CH Vichy, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CCSD, Accord Elsevier, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, and Université Francois Rabelais [Tours]

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, [SDV]Life Sciences [q-bio], education, Urology, Renal function, 030204 cardiovascular system & hematology, Kidney, Kidney transplant, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Extracorporeal Photopheresis, medicine, Humans, Risk factor, ComputingMilieux_MISCELLANEOUS, Kidney transplantation, Aged, Retrospective Studies, Heart transplantation, business.industry, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, Kidney Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], Concomitant, Photopheresis, Female, business, 030215 immunology
Abstract

Background - Extracorporeal photopheresis (ECP) has shown encouraging results in the prevention of allograft rejection in heart transplantation. However, the role of ECP in kidney transplant (KT) rejection needs to be determined. Methods - This multicentre retrospective study included 33 KT recipients who were treated with ECP for allograft rejection (23 acute antibody-mediated rejections (AMRs), 2 chronic AMRs and 8 acute cellular rejections (ACRs)). The ECP indications were KT rejection in patients who were resistant to standard therapies (n = 18) or in patients for whom standard therapies were contraindicated because of concomitant infections or cancers (n = 15). Results - At 12 months (M12) post-ECP, 11 patients (33%) had a stabilization of kidney function with a graft survival rate of 61%. The Banff AMR score (g + ptc + v) was a risk factor for graft loss at M12 (HR 1.44 [1.01-2.05], p 0.05). The factorial mixed data analysis identified 2 clusters. Patients with a functional graft at M12 tended to have cellular and/or chronic rejections. Patients with graft loss at M12 tended to have acute rejections and/or AMR; higher serum creatinine levels; DSA levels and histologic scores of AMR; and a longer delay between the rejection and ECP start than those of patients with functional grafts. Conclusions - ECP may be helpful to control ACR or moderate AMR in KT recipients presenting concomitant opportunistic infections or malignancies when it is initiated early.

Published
2019
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6. Belatacept in renal transplant recipient with mild immunologic risk factor: A pilot prospective study (BELACOR)

Author

Laurent Salomon, Stéphanie Malard, Thomas Robert, Caroline Pilon, Emmanuelle Boutin, Florence Canoui-Poitrine, Antoine Durrbach, Marie Matignon, Anissa Zarour, Claire Leibler, Anissa Moktefi, Philippe Grimbert, Chloé Samson, Pierre-André Natella, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), service Anatomie et Cytologie Pathologique, Hôpital Henri Mondor, Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Génomique Fonctionnelle, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), IMRB - CEPIA/'Clinical Epidemiology And Ageing : Geriatrics, Primary Care and Public Health' [Créteil] (U955 Inserm - UPEC), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Necker - Enfants Malades [AP-HP], Clinical Research Unit (URC Mondor), Hôpitaux Universitaires Henri-Mondor AP-HP, Néphrologie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire de Biomécanique et Mécanique des Chocs (LBMC UMR T9406), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut Français des Sciences et Technologies des Transports, de l'Aménagement et des Réseaux (IFSTTAR), Service de néphrologie, dialyse, aphérèses et transplantation, and CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Graft Rejection, Male, Pilot Projects, kidney transplantation/nephrology, immunosuppression/immune modulation, 030230 surgery, Kidney Function Tests, law.invention, Postoperative Complications, 0302 clinical medicine, Randomized controlled trial, Isoantibodies, Risk Factors, law, Immunology and Allergy, Medicine, Pharmacology (medical), Prospective Studies, immunosuppressant - fusion proteins and monoclonal antibodies, Prospective cohort study, belatacept, Incidence (epidemiology), Graft Survival, clinical trial, Middle Aged, Prognosis, Female, rejection, Immunosuppressive Agents, Glomerular Filtration Rate, medicine.drug, medicine.medical_specialty, Urology, Renal function, clinical research/practice, Belatacept, Abatacept, 03 medical and health sciences, antibody-mediated (ABMR), panel reactive antibody (PRA), Humans, Risk factor, Retrospective Studies, Transplantation, business.industry, Kidney Transplantation, Calcineurin, Clinical trial, Kidney Failure, Chronic, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Follow-Up Studies
Abstract

The benefit of belatacept on antibody-mediated rejection (ABMR) incidence after kidney transplant with preformed donor-specific antibodies (DSAs) has never been assessed. Between 2014 and 2016, we conducted a multicenter prospective clinical trial with 49 patients to determine kidney allograft outcome in recipients with preformed DSAs (maximal mean fluorescence intensity 500 to 3000) treated with belatacept (BELACOR trial). Immunosuppressive strategy included antithymocyte globulin, belatacept, mycophenolate mofetil, and steroids. An ancillary control group was designed retrospectively, including patients fulfilling the same inclusion criteria treated with calcineurin inhibitors. In BELACOR group, no patient exhibited acute ABMR, patient and allograft survival at 1 year was 100% and 95.4%, respectively, and the estimated glomerular filtration rate was 53.2 mL/min/1.73 m2 . However, the 12-month incidence of acute T cell-mediated rejection was 25.4% (14.5% to 42.4%). Comparison with the control group showed significantly higher T cell-mediated rejection incidence only in the BELACOR group (P = .003). Considering the DSAs, the outcome was similar in the 2 groups except a significantly higher number of patients displayed a complete disappearance of class II DSAs in the BELACOR group (P = .001). Belatacept was not associated with an acute ABMR increased risk and may be considered as immunosuppressive strategy in transplant recipients with preformed DSAs (maximal mean fluorescence intensity 500 to 3000). Prospective randomized trials are needed to confirm these results.

Published
2019
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7. Estimated Glomerular Filtration Rate Bias in Participants with Severe Obesity Regardless of Deindexation

Author

Fitsum Guebre-Egziabher, Sandrine Lemoine, Charlotte Brunelle, Laurence Dubourg, Caroline C Pelletier, Laurent Juillard, Gabrielle Normand, Jouve Thomas, Service de néphrologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Université Grenoble Alpes (UGA), Morton K. Blaustein Department of Earth and Planetary Sciences [Baltimore], Johns Hopkins University (JHU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Laboratoire de Biologie Tissulaire et d'ingénierie Thérapeutique UMR 5305 (LBTI), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie, dialyse, aphérèses et transplantation, Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National de la Recherche Agronomique (INRA)

Subjects
Male, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), urologic and male genital diseases, surgery, 0302 clinical medicine, Endocrinology, body-composition, Risk Factors, Medicine, 030212 general & internal medicine, accurate, Aged, 80 and over, Body surface area, Kidney, Nutrition and Dietetics, Data Collection, Middle Aged, female genital diseases and pregnancy complications, Obesity, Morbid, medicine.anatomical_structure, Female, Glomerular Filtration Rate, medicine.drug, Adult, medicine.medical_specialty, Adolescent, Urology, Renal function, 030209 endocrinology & metabolism, equation, serum creatinine, Young Adult, 03 medical and health sciences, Endocrinology & Metabolism, Humans, Renal Insufficiency, Chronic, Aged, Retrospective Studies, Nutrition & Dietetics, business.industry, association, kidney-disease, Retrospective cohort study, medicine.disease, Obesity, gfr, ckd, Iohexol, business, Body mass index, Kidney disease
Abstract

International audience; Objective Morbid obesity is associated with a higher independent risk of chronic kidney disease (CKD). Estimated glomerular filtration rate (eGFR) has been evaluated in a limited number of study participants with severe obesity. Methods A total of 706 measured GFR (mGFR) results from 598 participants with obesity (BMI \textgreater= 35 kg/m(2)) were retrospectively collected. The performance of the Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, and deindexed eGFR were compared with mGFR from the gold standard technique (inuline or iohexol), adjusted (mGFRr) or nonadjusted (mGFR) to body surface area. Absolute bias, precision, and accuracy were calculated. Results Mean mGFRr (58 +/- 31 mL/min/1.73 m(2)) was significantly different from CKD-EPI and MDRD (P \textless 0.001). Mean mGFR (nonindexed) (70 +/- 40 mL/min) was significantly higher than mGFRr (P \textless 0.001). eGFR showed important biases and low accuracies for CKD-EPI and MDRD (10.7 +/- 10.7 and 12.2 +/- 13.7 mL/min/1.73 m(2); 78% vs. 75% respectively). Deindexation worsened bias and accuracy 30% (percentage of GFR estimates within 30% of mGFRr or mGFR) between eGFR and mGFR. Conclusions eGFR overestimates mGFR and is associated with important biases and inaccuracies in patients with severe obesity, and deindexing eGFR worsens the overestimation. These findings may have important implications in examining kidney function in patients with obesity.

Published
2019
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8. Pharmacokinetics of Prolonged-Release Once-Daily Formulations of Tacrolimus in De Novo Kidney Transplant Recipients: A Randomized, Parallel-Group, Open-Label, Multicenter Study

Author

Mirco Govoni, Paolo Malvezzi, Valérie Garrigue, Arnaud Del Bello, Yannick Le Meur, Giorgia Ciurlia, Silvia Geraci, Elisabeth Cassuto, Lionel Rostaing, Nassim Kamar, Gianluigi Poli, Gabriele Nicolini, Marie Essig, Christophe Mariat, Giovanni Piotti, Michel, Geneviève, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de néphrologie et transplantation rénale [Nice], Hôpital Pasteur [Nice] (CHU), Kidney and Pancreas Transplantation, Global Clinical Development, CHU Saint-Etienne, 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), Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Nephrologie-Transplantation Rénale et Hémodialyse [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Néphrologie, Dialyse et Transplantation (Hôpital Lapeyronie [Montpellier] CHU), Hôpital Lapeyronie [Montpellier] (CHU), Departements of nephrology and organ transplantation [Toulouse], Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Néphrologie et Transplantation d'organes, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Nice (CHU Nice), Service de néphrologie et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Département de Diabétologie, Urologie, Néphrologie et Endocrinologie (CHU-Grenoble), CHU Grenoble, CHRU Brest - Service de Nephrologie (CHU - BREST - Nephrologie), Lymphocyte B et Auto-immunité (LBAI), 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Néphrologie, and Hôpital Lapeyronnie

Subjects
Adult, Male, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Urology, Cmax, Biological Availability, 030230 surgery, 030226 pharmacology & pharmacy, Kidney transplant, Drug Administration Schedule, Tacrolimus, PR Tac, 03 medical and health sciences, 0302 clinical medicine, Therapeutic index, Pharmacokinetics, Prolonged release, medicine, Humans, Pharmacology (medical), Molecular Targeted Therapy, Prospective Studies, De novo kidney transplantation, ComputingMilieux_MISCELLANEOUS, Original Research, business.industry, Envarsus, Advagraf, General Medicine, Middle Aged, Kidney Transplantation, 3. Good health, Bioavailability, LCPT, Treatment Outcome, Multicenter study, Research Design, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, business, Immunosuppressive Agents
Abstract

Introduction Different prolonged-release formulations of tacrolimus are available. To date, the pharmacokinetic (PK) profile of LCP-tacrolimus (LCPT; Envarsus®) has not been compared with PR-Tac (Advagraf®) in de novo kidney transplant recipients. These profiles will guide clinical recommendations for the initiation and dose titration strategies of once-daily tacrolimus formulations. Methods This randomized, parallel-group, open-label, multicenter PK study randomized 75 de novo, adult, white kidney transplant recipients to LCPT 0.17 mg/kg/day (n = 37) or PR-Tac 0.20 mg/kg/day (n = 38) for 4 weeks. Dose adjustments were permitted to target a pre-defined therapeutic range based on measured trough blood concentrations. Results PK analysis (days 1, 3, 7 and 14) included 68 patients (LCPT, n = 33; PR-Tac, n = 35). Similar proportions of patients were within the pre-defined therapeutic tacrolimus trough blood concentration range, with

Published
2019
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9. Access to and characteristics of palliative care-related hospitalization in the management of end-stage renal disease patients on renal replacement therapy in France

Author

Sylvie Blanchard, Thierry Lobbedez, Cécile Couchoud, F. Chantrel, Rein registry, Olivier Moranne, Del Bello Arnaud, Jocelyne Maurizi-Balzan, Agence de la biomédecine [Saint-Denis la Plaine], Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, 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), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)

Subjects
Adult, Male, medicine.medical_specialty, Time Factors, Palliative care, medicine.medical_treatment, 030232 urology & nephrology, Disease, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Health Services Accessibility, End stage renal disease, Young Adult, 03 medical and health sciences, 0302 clinical medicine, death, Epidemiology, medicine, Humans, cancer, Registries, 030212 general & internal medicine, Renal replacement therapy, Intensive care medicine, Dialysis, Disease burden, Aged, Aged, 80 and over, end-stage renal disease, palliative care, business.industry, Mortality rate, General Medicine, Middle Aged, 3. Good health, Hospitalization, Renal Replacement Therapy, Treatment Outcome, Withholding Treatment, Nephrology, Kidney Failure, Chronic, Female, dialysis withdrawal, France, business
Abstract

International audience; AIM:Palliative care is seldom proposed to patients with end-stage renal disease (ESRD) despite a mortality rate and disease burden as high as among cancer patients. The aim of this study is to analyze the access of palliative care-related hospitalization in the management of patients on dialysis in France, by describing the characteristics of these hospitalizations, the clinical status of the concerned patients, and the use of palliative care in those stopping dialysis.METHODS:The French Renal Epidemiology and Information Network (REIN) registry includes data about 51 834 patients aged 20 years and older who began dialysis from 1 January 2008 to 31 December 2013, and were followed longitudinally until that date. Linkage to the anonymized national hospital discharge database allowed us to analyse hospitalizations associated with palliative care.RESULTS:During the follow-up period, 1865 patients (3.6%) had a palliative care-related hospitalization corresponding to a total of 3382 hospitalizations. Lower levels of serum albumin, active cancer, and impaired mobility were each independently associated with the probability of at least one such hospitalization. During the same period 4540 patients withdrew from dialysis (9% of the patients), 10% of them had a palliative care-related hospitalization.CONCLUSION:This study suggests that among ESRD patients, only a few resorted to palliative care-related hospitalization, even those withdrawing from dialysis. Cooperation between nephrologists and physicians trained in palliative care should be improved at least to the extent necessary to identify patients who should be referred to palliative care. Our study also highlights the need for more information on the current access to any kind of supportive care for dialysis patients.

Published
2017
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10. Switching renal transplant recipients to belatacept therapy: results of a real-life gradual conversion protocol

Author

Guillaume Rigault, Paolo Cravedi, Bénédicte Janbon, Tatiana Raskovalova, Clara Fischman, Lionel Rostaing, Marie Christine Jacob, Paolo Malvezzi, Thomas Jouve, Service de néphrologie, dialyse, aphérèses et transplantation, CHU Grenoble-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Department of Medicine, University of Washington [Seattle], Service d'immunologie [CHU Grenoble], and CHU de Grenoble

Subjects
Adult, Graft Rejection, Male, medicine.medical_specialty, T-Lymphocytes, [SDV]Life Sciences [q-bio], Urinary system, medicine.medical_treatment, Calcineurin Inhibitors, Immunology, Urology, Renal function, 030230 surgery, Chemokine CXCL9, Belatacept, Abatacept, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Humans, Immunology and Allergy, Drug Dosage Calculations, Aged, Retrospective Studies, B-Lymphocytes, Transplantation, Creatinine, Proteinuria, Drug Substitution, business.industry, Immunosuppression, Middle Aged, Kidney Transplantation, Transplant Recipients, Tacrolimus, 3. Good health, Calcineurin, chemistry, Acute Disease, Female, medicine.symptom, business, Immunologic Memory, Biomarkers, Immunosuppressive Agents, Follow-Up Studies, 030215 immunology, medicine.drug
Abstract

Conversion to belatacept immunosuppression is a therapeutic option for renal-transplant recipients with calcineurin inhibitors (CNI) toxicity, but it associates with high risk of acute rejection. Gradual conversion and serial immune monitoring with urinary chemokine CXCL9 may allow increasing safety of this maneuver. We converted kidney transplant recipients with signs of toxicity to CNI or other immunosuppressive drugs to belatacept over a 2-month period. We monitored renal function, metabolic profile, and circulating lymphocyte subsets. We also quantified urinary CXCL9 over a 12-month follow-up period. Between September 2016 and March 2017, 35 patients were successfully switched to belatacept immunosuppression at 3.3 (1.3-7.2) years after transplant. Two patients had a reversible rise in serum creatinine, associated with acute rejection in one case. Urinary CXCL9 increased before serum creatinine. After conversion, blood pressure and HbA1c significantly declined while eGFR and proteinuria remained stable. The percentage of circulating effector T cells and memory B cells significantly declined. Conversion from CNI to belatacept, in this setting, was feasible and safe, provided it was performed over a 2-month time-period. Monitoring urinary CXCL9 may further increase safety through earlier identification of patients at risk for acute rejection. The procedure associates with improved blood pressure, metabolic profile, and reduced circulating effector T and B cells.

Published
2019
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11. Acute Kidney Injury Predicts Major Adverse Outcomes in Diabetes: Synergic Impact With Low Glomerular Filtration Rate and Albuminuria

Author

Stéphanie Ragot, Vincent Rigalleau, X. Piguel, Samy Hadjadj, Jean-Michel Halimi, Elise Gand, P. Zaoui, Ronan Roussel, Pierre-Jean Saulnier, Richard Marechaud, Mathilde Monseu, 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), Immunologie antivirale systémique et cérébrale, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Déterminants génétiques du diabète de type 2 et de ses complications vasculaires ((U 695)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), 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, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Renal function, Type 2 diabetes, urologic and male genital diseases, Revascularization, Risk Factors, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Albuminuria, Humans, Myocardial infarction, Intensive care medicine, Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Advanced and Specialized Nursing, business.industry, Acute kidney injury, Acute Kidney Injury, Middle Aged, medicine.disease, Prognosis, 3. Good health, Diabetes Mellitus, Type 2, Cardiology, Female, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Biomarkers, Glomerular Filtration Rate
Abstract

OBJECTIVE Subjects with diabetes are prone to the development of cardiovascular and noncardiovascular complications. In separate studies, acute kidney injury (AKI), albuminuria, and low estimated glomerular filtration rate (eGFR) were shown to predict adverse outcomes, but, when considered together, their respective prognostic value is unknown. RESEARCH DESIGN AND METHODS Patients with type 2 diabetes consecutively recruited in the SURDIAGENE cohort were prospectively followed up for major diabetes-related events, as adjudicated by an independent committee: death (with cause), major cardiovascular events (myocardial infarction, stroke, congestive heart failure, amputation, and arterial revascularization), and renal failure (i.e., sustained doubling of serum creatinine level or end-stage renal disease). RESULTS Intrahospital AKI occurred in 411 of 1,371 patients during the median follow-up period of 69 months. In multivariate analyses, AKI was significantly associated with cardiovascular and noncardiovascular death, including cancer-related death. In multivariate analyses, AKI was a powerful predictor of major adverse cardiovascular events, heart failure requiring hospitalization, myocardial infarction, stroke, lower-limb amputation or revascularization, and carotid artery revascularization. AKI, eGFR, and albuminuria, even when simultaneously considered in multivariate models, predicted all-cause and cardiovascular deaths. All three renal biomarkers were also prognostic of most adverse outcomes and of the risk of renal failure. CONCLUSIONS AKI, low eGFR, and elevated albuminuria, separately or together, are compelling biomarkers of major adverse outcomes and death in diabetes.

Published
2015
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12. Impact of anti-insulin antibodies on islet transplantation outcome: data from the GRAGIL Network

Author

Lablanche, S., Borot, S., Thaunat, O., Bayle, F., Badet, L., Morelon, E., Thivolet, Charles, Wojtusciszyn, A., Frimat, L., Kessler, L., Penfornis, A., Brault, C., Colin, C., Bosco, D., Berney, T., Benhamou, P. Y., Network, Gragil, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire [Grenoble] (CHU), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie, rhumatologie et dermatologie pédiatriques [Hôpital Femme Mère Enfant, HCL], Hospices Civils de Lyon (HCL)-Hôpital Mère Enfant, Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, Pôle Information Médicale Evaluation Recherche (IMER), and Hospices Civils de Lyon (HCL)

Subjects
Blood Glucose, Adult, Male, medicine.medical_specialty, endocrine system diseases, Insulin Antibodies, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Islets of Langerhans Transplantation, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, Hypoglycemia, Pharmacokinetics, Internal medicine, Insulin Antibodies/analysis/*physiology, Medicine, Humans, Retrospective Studies, Transplantation, geography, Type 1 diabetes, geography.geographical_feature_category, ddc:617, business.industry, Insulin, Blood Glucose/analysis, Middle Aged, Islet, medicine.disease, 3. Good health, medicine.anatomical_structure, Endocrinology, Treatment Outcome, Metabolic control analysis, Case-Control Studies, Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Insulin Resistance, business, Pancreas
Abstract

International audience; BACKGROUND: In patients with type 1 diabetes, insulin antibodies (IA), altering the pharmacokinetics of circulating insulin, might be associated with high glucose concentration, prolonged hypoglycemia, and higher insulin requirement. The impact of IA on islet transplantation has never been explored. Our aim was to evaluate islet transplantation results at 1 year according to the presence of IA. METHODS: Our work is a retrospective, case-control study, comparing IA-negative and IA-positive patients among the cohort of patients with type 1 diabetes transplanted within the Swiss-French GRAGIL network between 2003 and 2010. RESULTS: Data about IA were available for 17 patients. Before islet transplantation, 10 patients (59%) were screened positive for IA. At 12 months after transplantation, IA-positive patients reached insulin independence less frequently than IA-negative patients (cumulative incidence of insulin independence, 22.2% vs. 71.4%; P=0.02); beta score was \textgreater/=7 in 43% of IA-negative patients versus 0% in IA-positive patients (P=0.022). When comparing IA-positive patients with IA-negative patients, insulin dose was 0.15 U/kg (0.10-0.18 U/kg) versus 0.01 U/kg (0-0.09 U/kg) (P=0.2); HbA1c was 6.1% (5.8%-6.3%) versus 6.1% (5.9%-6.8%) (P=0.16); basal C-peptide level was 460 rhomol/L (350-510 rhomol/L) versus 265 rhomol/L (177-405 rhomol/L) (P=0.28); occurrence of hypoglycemia was 12.5% versus 16.5% (P=0.9); and homeostatic model assessment insulin resistance was 1.25 (1-2.4) versus 0.7 (0.52-0.92) (P=0.01). CONCLUSION: After islet transplantation, IA-positive patients achieved insulin independence less frequently, exhibiting lower beta score and higher homeostatic model assessment insulin resistance compared with IA-negative patients. However, in both groups, islet transplantation restored good glycemic control and drastically reduced hypoglycemia and insulin requirements.

Published
2014
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13. Predictive diagnostic of chronic allograft dysfunction using urinary proteomics analysis

Author

Rachel Tetaz, Candice Trocmé, N. Pinel, Mathieu Roustit, Philippe Zaoui, François Bayle, Bertrand Toussaint, 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), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Département d'anatomie et cythologie pathologique, CHU Grenoble-Hôpital Michallon, Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, CHU Necker - Enfants Malades [AP-HP] - Assistance publique - Hôpitaux de Paris (AP-HP), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF) - Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP) - IMAG - Centre National de la Recherche Scientifique (CNRS) - Université Grenoble Alpes (UGA), CHU Grenoble - Hôpital Michallon, Service de néphrologie, and Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble

Subjects
Graft Rejection, Male, Proteomics, MESH: Primary Graft Dysfunction, Pathology, 030232 urology & nephrology, MESH : Aged, Urine, 030226 pharmacology & pharmacy, Gastroenterology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Kidney Transplantation, MESH : Proteomics, 0302 clinical medicine, Medicine, MESH : Female, Stage (cooking), MESH: Aged, Kidney, MESH: Middle Aged, MESH: Protein Array Analysis, MESH: Proteomics, General Medicine, MESH : Protein Array Analysis, Middle Aged, MESH : Adult, MESH : Primary Graft Dysfunction, MESH: Predictive Value of Tests, 3. Good health, medicine.anatomical_structure, surgical procedures, operative, MESH: Kidney Failure, Chronic, Cohort, Biomarker (medicine), Female, MESH : Sensitivity and Specificity, Adult, medicine.medical_specialty, Urinary system, MESH : Male, Protein Array Analysis, MESH: Graft Rejection, Sensitivity and Specificity, MESH : Kidney Failure, Chronic, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Humans, MESH : Middle Aged, MESH : Predictive Value of Tests, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Aged, Transplantation, Proteomic Profile, MESH: Humans, business.industry, MESH : Humans, MESH : Graft Rejection, MESH: Adult, Kidney Transplantation, MESH: Sensitivity and Specificity, MESH: Male, Kidney Failure, Chronic, MESH : Kidney Transplantation, Primary Graft Dysfunction, business, MESH: Female
Abstract

International audience; BACKGROUND: Kidney transplant Chronic Allograft Dysfunction (CAD), a major cause of long-term graft failure, is currently diagnosed at a late and irreversible stage by graft biopsies. Our goal was to identify predictive urinary biomarkers of CAD before renal lesions appeared by analysis of the urine proteomic profile. METHODS/METHODS: Twenty-nine urinary samples withdrawn three months post-transplant were analyzed by SELDI-TOF technology. CAD development was evaluated by serum creatinine level and confirmed by allograft biopsy one year after transplantation. Comparison of protein profile of both groups revealed 18 biomarkers predictive of CAD occurrence. RESULTS: The biomarker demonstrating the highest diagnostic performance was a protein of 8860 Da that predicted CAD with a sensitivity of 93% and a specificity of 65%. Moreover combination of these biomarkers in two multivariate analyses improved the diagnostic potential of CAD. Relevance of these individual biomarkers and a decisional algorithm constituted of 3 proteins was confirmed in an independent cohort of patients with undetermined CAD status one year post-transplant. CONCLUSIONS: These non invasive biomarkers, detected as soon as three months post-grafting, allowed identification of patients who would develop CAD as late as 4 years after graft. Systematic measurement of these biomarkers would greatly improve the management of immunosuppressive therapy of kidney grafted patients.

Published
2012

14. Impact of the Number of Infusions on 2-Year Results of Islet-After-Kidney Transplantation in the GRAGIL Network

Author

Thierry Berney, Laurence Kessler, Anne Wojtusciszyn, Raphael P. H. Meier, Cyrille Colin, Sophie Borot, Sandrine Demuylder-Mischler, François Bayle, Charles Thivolet, Yannick D. Muller, Pierre-Yves Benhamou, Luc Frimat, Domenico Bosco, Alfred Penfornis, Emmanuel Morelon, Coralie Brault, Philippe Morel, Laurianne Giovannoni, Christian Toso, Nadja Niclauss, Lionel Badet, Géraldine Parnaud, Department of Surgery, University of Geneva [Switzerland], Centre de pharmacologie et innovation dans le diabète (CPID), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre National de la Recherche Scientifique (CNRS), Pôle Information Médicale Evaluation Recherche (IMER), Hospices Civils de Lyon (HCL), Etude des Civilisations de l'Antiquité (UMR 7044), Centre National de la Recherche Scientifique (CNRS)-Université Marc Bloch - Strasbourg II-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA)), Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Endocrinology, Nutritional Diseases, Hôpitaux Universitaires de Strasbourg, Department of Transplantation Medicine, Hôpital Edouard Herriot [CHU - HCL], Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service d'Endocrinologie Diabete Nutrition, Université de Lyon, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie, Pôle Digidune, CHU Grenoble, Centre de pharmacologie et innovation dans le diabète ( CPID ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Centre National de la Recherche Scientifique ( CNRS ), Pôle Information Médicale Evaluation Recherche ( IMER ), Hospices Civils de Lyon ( HCL ), Etude des Civilisations de l'Antiquité ( UMR 7044 ), Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Service de néphrologie, Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hôpital universitaire de Nancy, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Laboratoire de bioénergétique fondamentale et appliquée ( LBFA ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), Hamant, Sarah, Université de Genève = University of Geneva (UNIGE), Étude des Civilisations de l'Antiquité : de la Préhistoire à Byzance (ARCHIMEDE), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université Marc Bloch - Strasbourg II-Centre National de la Recherche Scientifique (CNRS), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
Blood Glucose, Male, Time Factors, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, endocrine system diseases, medicine.medical_treatment, Islets of Langerhans Transplantation, 030230 surgery, Gastroenterology, Diabetes Mellitus, Type 1/drug therapy/metabolism/surgery, 0302 clinical medicine, Medicine, Insulin, Longitudinal Studies, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, geography.geographical_feature_category, C-Peptide, Immunosuppression, Islets of Langerhans Transplantation/methods/physiology, Middle Aged, Islet, 3. Good health, Treatment Outcome, Insulin/therapeutic use, C-Peptide/blood, 030211 gastroenterology & hepatology, Female, France, Adult, medicine.medical_specialty, endocrine system, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Hemoglobin A, Glycosylated/metabolism, Internal medicine, Diabetes mellitus, Humans, ddc:610, Glycemic, Retrospective Studies, Glycated Hemoglobin, Transplantation, geography, Blood Glucose/metabolism, business.industry, Kidney Transplantation/physiology, Retrospective cohort study, medicine.disease, Kidney Transplantation, Surgery, Diabetes Mellitus, Type 1, Basal (medicine), business
Abstract

International audience; BACKGROUND.: Insulin independence after islet transplantation is generally achieved after multiple infusions. However, single infusion would increase the number of recipients. Our aim was to evaluate the results of islet-after-kidney transplantation according to the number of infusions. METHODS.: Islets were isolated at the Geneva University, shipped, and transplanted into French patients from the Swiss-French GRAGIL network, on the "Edmonton" immunosuppression protocol between 2004 and 2010. RESULTS.: Nineteen patients were transplanted with 33 preparations. Fifteen patients reached 24 months follow-up; eight subjects were single-graft recipients and seven were double-graft recipients. Finally, single-graft recipients received a median of 5312 islet equivalents/kg (5186-6388) vs. 10,564 (10,054-11,375) for double-graft recipients (P=0.0003) with similar islet mass at first infusion. Insulin independence was achieved in five of eight single-graft subjects (62.5%) versus five of seven in double-graft subjects (71.4%), not significant. Median insulin independence duration was 4.7 (3.1-15.2) months after one infusion vs. 19 (9.6-20.8) months after two infusions (not significant). At 24 months posttransplant, comparing single- with double-graft patients, insulin doses were 0.23 (0.11-0.34) U/kg vs. 0.02 (0.0-0.23) U/kg, P=0.11; HbA1c was 6.5% (5.9%-6.8%) vs. 6.2% (5.9%-6.3%), P=0.16; and basal C-peptide was 302 (143-480) pmol/L vs. 599 (393-806) pmol/L, P=0.05. Only 37.5% of single-graft patients had a β-score ≥4 compared with 100% of double-graft patients (P=0.03). Two recipients experienced postinfusion bleeding, and two patients (13%) showed renal dysfunction in the absence of biopsy-proven rejection. CONCLUSIONS.: One infusion achieves good glycemic control and sometimes insulin independence. However, double-graft patients remain insulin-free longer, tend to have lower HbA1c, and show better graft function 24 months after transplant.

Published
2011
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15. Renal function with delayed or immediate cyclosporine microemulsion in combination with enteric-coated mycophenolate sodium and steroids: results of follow up to 30 months post-transplant

Author

Mourad , Georges, Karras , Alexandre, Kamar , Nassim, Garrigue , Valérie, Legendre , Christophe, Lefrançois , Nicole, Charpentier , Bernard, Bourbigot , Bernard, Pouteil-Noble , Claire, Bayle , François, Lebranchu , Yvon, Mariat , Christophe, Le Meur , Yann, Kessler , Michèle, Moulin , Bruno, Ducloux , Didier, Delahousse , Michel, Lang , Philippe, Merville , Pierre, Chaouche-Teyara , Kamel, Rostaing , Lionel, Service de Pédiatrie spécialisée, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, 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 - Hypertension Artérielle Dialyse - Transplantation, Service de transplantation, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Service de néphrologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Greffes d'Epitheliums et Regulation de l'Activation Lymphocytaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Service de néphrologie et transplantation, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Service de néphrologie, dialyse, aphérèses et transplantation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, 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 et tranplantation, CHU Saint-Etienne-Hôpital nord, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service de Néphrologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Néphrologie et Transplantation, CHU Strasbourg, Service d'urologie, andrologie et transplantation rénale, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de transplantation rénale, Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Novartis France SAS, Novartis Pharma S.A.S., The French Myriade FR01 Study Group, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie et immunologie clinique, Hôpital Bretonneau-Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Saas, Philippe, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Lapeyronie, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Hospices Civils de Lyon ( HCL ) -Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ) -Hôpital de la Cavale Blanche - CHRU Brest ( CHU - BREST ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Hôpital Bretonneau-Université de Tours-CHRU Tours, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de Néphrologie et Urologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 )

Subjects
Male, Time Factors, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Male, MESH: Creatinine, MESH: Tablets, Enteric-Coated, Kidney, Kidney Function Tests, MESH: Cyclosporine, MESH: Kidney Transplantation, MESH : Cyclosporine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, MESH : Middle Aged, MESH : Female, MESH : Immunosuppressive Agents, MESH: Middle Aged, MESH: Humans, MESH : Drug Therapy, Combination, MESH : Humans, MESH : Kidney Function Tests, MESH: Time Factors, MESH : Creatinine, MESH : Follow-Up Studies, MESH: Follow-Up Studies, MESH: Kidney, MESH : Tablets, Enteric-Coated, Middle Aged, Kidney Transplantation, MESH : Kidney, MESH: Male, MESH: Drug Therapy, Combination, MESH: Kidney Function Tests, Creatinine, Cyclosporine, MESH : Kidney Transplantation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Drug Therapy, Combination, Female, Tablets, Enteric-Coated, MESH: Immunosuppressive Agents, MESH: Female, Immunosuppressive Agents, MESH : Time Factors, Follow-Up Studies
Abstract

International audience; BACKGROUND: In the multicenter, open-label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA-ME, day 0) or delayed CsA-ME (day 6) with enteric-coated mycophenolate sodium (EC-MPS), steroids and interleukin-2 receptor induction. One-yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post-transplant. METHODS: All patients completing the one-yr core study on-treatment were eligible to enter the extension study. RESULTS: Of the 203 patients, 153 completed the core trial on-treatment; 144 (94%) entered the extension study with a minimum follow-up of one yr (73 early CsA-ME, 71 delayed CsA-ME). In 75% of patients receiving EC-MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post-transplant and was similar in the early and delayed CsA-ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA-ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events. CONCLUSION: These results suggest that a regimen of CsA-ME, EC-MPS and steroids results in excellent survival rates with stable renal function over a mean follow-up of 30 months. Immediate introduction of CsA-ME has no deleterious effect on long-term renal function, even among patients with delayed graft function.

Published
2007
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