Charpentier B.,University Paris - Sud |
Medina Pestana J.O.,Hospital Do Rim e Hipertensao |
Del C. Rial M.,Institute Nefrologia |
Rostaing L.,University Hospital U563 BMT |
And 7 more authors.
American Journal of Transplantation | Year: 2013
Patients in the BENEFIT-EXT study received extended criteria donor kidneys and a more intensive (MI) or less intensive (LI) belatacept immunosuppression regimen, or cyclosporine A (CsA). Patients who remained on assigned therapy through year 3 were eligible to enter a long-term extension (LTE) study. Three hundred four patients entered the LTE (n = 104 MI; n = 113 LI; n = 87 CsA), and 260 continued treatment through year 5 (n = 91 MI; n = 100 LI; n = 69 CsA). Twenty patients died during the LTE (n = 5 MI; n = 9 LI; n = 6 CsA), and eight experienced graft loss (n = 2 MI; n = 1 LI; n = 5 CsA). Three patients experienced an acute rejection episode (n = 2 MI; n = 1 LI). The incidence rate of serious adverse events, viral infections and fungal infections was similar across groups during the LTE. There were four cases of posttransplant lymphoproliferative disorder (PTLD) from the beginning of the LTE to year 5 (n = 3 LI; n = 1 CsA); two of three PTLD cases in the LI group were in patients who were seronegative for Epstein-Barr virus (EBV(-)) at transplantation. Mean ± SD calculated GFR at year 5 was 55.9 ± 17.5 (MI), 59.0 ± 29.1 (LI) and 44.6 ± 16.4 (CsA) mL/min/1.73 m2. Continued treatment with belatacept was associated with a consistent safety profile and sustained improvement in renal function versus CsA over time. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
Pestana J.O.M.,Hospital Do Rim e Hipertensao Unifesp |
Grinyo J.M.,University of Barcelona |
Vanrenterghem Y.,University Hospital Leuven |
Becker T.,Medizinische Hochschule Hanover |
And 15 more authors.
American Journal of Transplantation | Year: 2012
Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population. Three-year results from the BENEFIT-EXT study confirm the durability of the renal function benefits of belatacept over time compared to cyclosporine, while providing comparable 3-year patient/graft survival and balancing risks associated with belatacept in recipients of extended criteria donor kidneys. © copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.
Durrbach A.,University Paris - Sud |
Pestana J.M.,Hospital Do Rim e Hipertensao Unifesp |
Pearson T.,Emory University |
Vincenti F.,University of California at San Francisco |
And 8 more authors.
American Journal of Transplantation | Year: 2010
Recipients of extended criteria donor (ECD) kidneys are at increased risk for graft dysfunction/loss, and may benefit from immunosuppression that avoids calcineurin inhibitor (CNI) nephrotoxicity. Belatacept, a selective costimulation blocker, may preserve renal function and improve long-term outcomes versus CNIs. BENEFIT-EXT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial - EXTended criteria donors) is a 3-year, Phase III study that assessed a more (MI) or less intensive (LI) regimen of belatacept versus cyclosporine in adult ECD kidney transplant recipients. The coprimary endpoints at 12 months were composite patient/graft survival and a composite renal impairment endpoint. Patient/graft survival with belatacept was similar to cyclosporine (86% MI, 89% LI, 85% cyclosporine) at 12 months. Fewer belatacept patients reached the composite renal impairment endpoint versus cyclosporine (71% MI, 77% LI, 85% cyclosporine; p = 0.002 MI vs. cyclosporine; p = 0.06 LI vs. cyclosporine). The mean measured glomerular filtration rate was 4-7 mL/min higher on belatacept versus cyclosporine (p = 0.008 MI vs. cyclosporine; p = 0.1039 LI vs. cyclosporine), and the overall cardiovascular/metabolic profile was better on belatacept versus cyclosporine. The incidence of acute rejection was similar across groups (18% MI; 18% LI; 14% cyclosporine). Overall rates of infection and malignancy were similar between groups; however, more cases of posttransplant lymphoproliferative disorder (PTLD) occurred in the CNS on belatacept. ECD kidney transplant recipients treated with belatacept-based immunosuppression achieved similar patient/graft survival, better renal function, had an increased incidence of PTLD, and exhibited improvement in the cardiovascular/metabolic risk profile versus cyclosporine-treated patients. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.
Rostaing L.,French Institute of Health and Medical Research |
Massari P.,Hospital Privado Centro Medico Of Cordoba |
Garcia V.D.,Hospital Dom Vicente Scherer |
Mancilla-Urrea E.,Instituto Nacional Of Cardiologia Ignacio |
And 8 more authors.
Clinical Journal of the American Society of Nephrology | Year: 2011
Background and objectives: Prolonged use of calcineurin inhibitors (CNIs) in kidney transplant recipients is associated with renal and nonrenal toxicity and an increase in cardiovascular risk factors. Belatacept-based regimens may provide a treatment option for patients who switch from CNI-based maintenance immunosuppression. Design, setting, participants, & measurements: This is a randomized, open-label Phase II trial in renal transplant patients with stable graft function and receiving a CNI-based regimen. Patients who were ≥6 months but ≤36 months after transplantation were randomized to either switch to belatacept or continue CNI treatment. All patients received background maintenance immunosuppression. The primary end point was the change in calculated GFR (cGFR) from baseline to month 12. Results: Patients were randomized either to switch to belatacept (n = 84) or to remain on a CNI-based regimen (n = 89). At month 12, the mean (SD) change from baseline in cGFR was higher in the belatacept group versus the CNI group. Six patients in the belatacept group had acute rejection episodes, all within the first 6 months; all resolved with no allograft loss. By month 12, one patient in the CNI group died with a functioning graft, whereas no patients in the belatacept group had graft loss. The overall safety profile was similar between groups. Conclusions: The study identifies a potentially safe and feasible method for switching stable renal transplant patients from a cyclosporine- or tacrolimus-based regimen to a belatacept-based regimen, which may allow improved renal function in patients currently treated with CNIs. Copyright © 2011 by the American Society of Nephrology.
PubMed | University of Minnesota, University Hospitals Leuven, University of Barcelona, Institute Nefrologia and 6 more.
Type: Journal Article | Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons | Year: 2016
In the Belatacept Evaluation of Nephroprotection and Efficacy as First-Line Immunosuppression Trial-Extended Criteria Donors (BENEFIT-EXT), extended criteria donor kidney recipients were randomized to receive belatacept-based (more intense [MI] or less intense [LI]) or cyclosporine-based immunosuppression. In prior analyses, belatacept was associated with significantly better renal function compared with cyclosporine. In this prospective analysis of the intent-to-treat population, efficacy and safety were compared across regimens at 7 years after transplant. Overall, 128 of 184 belatacept MI-treated, 138 of 175 belatacept LI-treated and 108 of 184 cyclosporine-treated patients contributed data to these analyses. Hazard ratios (HRs) comparing time to death or graft loss were 0.915 (95% confidence interval [CI] 0.625-1.339; p = 0.65) for belatacept MI versus cyclosporine and 0.927 (95% CI 0.634-1.356; p = 0.70) for belatacept LI versus cyclosporine. Mean estimated GFR (eGFR) plus or minus standard error at 7 years was 53.9 1.9, 54.2 1.9, and 35.3 2.0 mL/min per 1.73 m
Grinyo J.,University of Barcelona |
Alberu J.,Instituto Nacional Of Ciencias Medicas Y Nutricion Salvador Zubiran |
Contieri F.L.C.,Hospital University Evangelico Of Curitiba |
Manfro R.C.,Hospital Of Clinicas Of Porto Alegre |
And 8 more authors.
Transplant International | Year: 2012
Kidney transplant recipients who switched from a calcineurin inhibitor (CNI) to belatacept demonstrated higher calculated glomerular filtration rates (cGFRs) at 1 year in a Phase II study. This report addresses whether improvement was sustained at 2 years in the long-term extension (LTE). Patients receiving cyclosporine or tacrolimus were randomized to switch to belatacept or continue CNI. Of 173 randomized patients, 162 completed the 12-month main study and entered the LTE. Two patients (n = 1 each group) had graft loss between Years 1-2. At Year 2, mean cGFR was 62.0 ml/min (belatacept) vs. 55.4 ml/min (CNI). The mean change in cGFR from baseline was +8.8 ml/min (belatacept) and +0.3 ml/min (CNI). Higher cGFR was observed in patients switched from either cyclosporine (+7.8 ml/min) or tacrolimus (+8.9 ml/min). The frequency of acute rejection in the LTE cohort was comparable between the belatacept and CNI groups by Year 2. All acute rejection episodes occurred during Year 1 in the belatacept patients and during Year 2 in the CNI group. There were more non-serious mucocutaneous fungal infections in the belatacept group. Switching to a belatacept-based regimen from a CNI-based regimen resulted in a continued trend toward improved renal function at 2 years after switching. © 2012 The Authors. Transplant International © 2012 European Society for Organ Transplantation.
Larsen C.P.,Emory University |
Grinyo J.,University of Barcelona |
Medina-Pestana J.,Hospital Do Rim e Hipertensao Unifesp |
Vanrenterghem Y.,University Hospital Leuven |
And 11 more authors.
Transplantation | Year: 2010
Background. At 1 year, belatacept was associated with similar patient/graft survival, better renal function, and an improved cardiovascular/metabolic risk profile versus cyclosporine A (CsA) in the Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial (BENEFIT) and Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial-EXTended criteria donors (BENEFIT-EXT) studies. Acute rejection was more frequent with belatacept in BENEFIT. Posttransplant lymphoproliferative disorder (PTLD)-specifically central nervous system PTLD-was observed more frequently in belatacept-treated patients. This analysis assesses outcomes from BENEFIT and BENEFIT-EXT after 2 years of treatment. Methods. Patients received a more intensive (MI) or a less intensive (LI) regimen of belatacept or a CsA-based regimen. Results. Four hundred ninety-three of 666 patients (74%) in BENEFIT and 347 of 543 (64%) in BENEFIT-EXT completed 2 years of treatment. The proportion of patients who survived with a functioning graft was similar across groups (BENEFIT: 94% MI, 95% LI, and 91% CsA; BENEFIT-EXT: 83% MI, 84% LI, and 83% CsA). Belatacept's renal benefits were sustained, as evidenced by a 16 to 17 mL/min (BENEFIT) and an 8 to 10 mL/min (BENEFIT-EXT) higher calculated glomerular filtration rate in the belatacept groups versus CsA. There were few new acute rejection episodes in either study between years 1 and 2. Because PTLD risk was highest in Epstein-Barr virus (EBV) (-) patients, an efficacy analysis of EBV (+) patients was performed and was consistent with the overall population results. There were two previously reported cases of PTLD in each study between years 1 and 2 in the belatacept groups. The overall balance of safety and efficacy favored the LI over the MI regimen. Conclusions. At 2 years, belatacept-based regimens sustained better renal function, similar patient/graft survival, and an improved cardiovascular/metabolic risk profile versus CsA; outcomes that were maintained in EBV (+) patients. No new safety signals emerged. © 2010 by Lippincott Williams & Wilkins.
PubMed | University of Barcelona, Institute Nefrologia, Lakeshore Hospital, Balboa Institute of Transplantation and 5 more.
Type: | Journal: American journal of kidney diseases : the official journal of the National Kidney Foundation | Year: 2016
In a phase 2 study, kidney transplant recipients of low immunologic risk who switched from a calcineurin inhibitor (CNI) to belatacept had improved kidney function at 12 months postconversion versus those continuing CNI therapy, with a low rate of acute rejection and no transplant loss.36-month follow-up of the intention-to-treat population.CNI-treated adult kidney transplant recipients with stable transplant function (estimated glomerular filtration rate [eGFR], 35-75mL/min/1.73mAt 6 to 36 months posttransplantation, patients were randomly assigned to switch to belatacept-based immunosuppression (n=84) or continue CNI-based therapy (n=89).Safety was the primary outcome. eGFR, acute rejection, transplant loss, and death were also assessed.Treatment exposure-adjusted incidence rates for safety, repeated-measures modeling for eGFR, Kaplan-Meier analyses for efficacy.Serious adverse events occurred in 33 (39%) belatacept-treated patients and 36 (40%) patients in the CNI group. Treatment exposure-adjusted incidence rates for serious infections (belatacept vs CNI, 10.21 vs 9.31 per 100 person-years) and malignancies (3.01 vs 3.41 per 100 person-years) were similar. More patients in the belatacept versus CNI group had any-grade viral infections (14.60 vs 11.00 per 100 person-years). No posttransplantation lymphoproliferative disorder was reported. Belatacept-treated patients had a significantly greater estimated gain in mean eGFR (1.90 vs 0.07mL/min/1.73mExploratory post hoc analysis with a small sample size.Switching patients from a CNI to belatacept may represent a safe approach to immunosuppression and is being further explored in an ongoing phase 3b trial.
Cura C.I.,CONICET |
Lattes R.,Institute Nefrologia |
Nagel C.,Hospital Universitario Fundacion Favaloro |
Gimenez M.J.,Polytechnic University of Valencia |
And 6 more authors.
American Journal of Transplantation | Year: 2013
Organ transplantation (TX) is a novel transmission modality of Chagas disease. The results of molecular diagnosis and characterization of Trypanosoma cruzi acute infection in naïve TX recipients transplanted with organs from infected deceased donors are reported. Peripheral blood and cerebrospinal fluid samples from the TX recipients of organs from infected donors were prospectively and sequentially studied for detection of T. cruzi by means of kinetoplastid DNA polymerase chain reaction (kDNA-PCR). In positive blood samples, a PCR algorithm for identification of T. cruzi Discrete Typing Units (DTUs) and quantitative real-time PCR (qPCR) to quantify parasitic loads were performed. Minicircle signatures of T. cruzi infecting populations were also analyzed using restriction fragment length polymorphism (RFLP)-PCR. Eight seronegative TX recipients from four infected donors were studied. In five, the infection was detected at 68.4 days post-TX (36-98 days). In one case, it was transmitted to two of three TX recipients. The comparison of the minicircle signatures revealed nearly identical RFLP-PCR profiles, confirming a common source of infection. The five cases were infected by DTU TcV. This report reveals the relevance of systematic monitoring of TX recipients using PCR strategies in order to provide an early diagnosis allowing timely anti-trypanosomal treatment. Polymerase chain reaction strategies allow for the early diagnosis of acute Chagas disease in naïve recipients transplanted with organs from Trypanosoma cruzi-infected donors. See editorial by Machado on page 3065. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.
Dominguez M.,Centro Iberoamericano Of Biodiversidad Cibio |
Sanz A.,University of Habana |
Chavez J.,Institute Nefrologia |
Almaguer N.,University of Habana
Herpetologica | Year: 2010
We describe the gonadal and fat-body cycles and their relationship to environmental factors for Cuban female Anolis lucius (Polychrotidae). We obtained monthly samples of lizards from the karstic caves at Boca de Jaruco, Havana, Cuba. The lizards reached sexual maturity at 45.0 mm snoutvent length and at approximately 7 mo of age. Female A. lucius showed seasonal reproduction from March to August. The nonreproductive season occurred from September to February, as identified by the absence of active ovogenesis. Vitellogenic ovaries, and almost all females having one or two oviductal eggs, characterized the peak reproductive interval from May to August. In contrast, fat-body mass diminished from May to July and reached its highest values from September to January. The clutch size is one egg per oviposition, and oviposition events occurred from July to September. Increased photoperiod and environmental temperature induced ovarian activity. © 2010 by the Herpetologists' League, Inc.