RESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its resulting disease, coronavirus disease 2019 (COVID-19), has spread to millions of people worldwide. Preliminary data from organ transplant recipients have shown reduced seroconversion rates after the administration of different SARS-CoV-2 vaccination platforms. However, it is unknown whether different vaccination platforms provide different levels of protection against SARS-CoV-2. To answer this question, we prospectively studied 431 kidney and liver transplant recipients (kidney: n = 230; liver: n = 201) who received either the ChAdOx1 vaccine (n = 148) or the BNT-162b2 vaccine (n = 283) and underwent an assessment of immunoglobulin M/immunoglobulin G spike antibody levels. The primary objective of the study is to directly compare the efficacy of two different vaccine platforms in solid organ transplant recipients by measuring of immunoglobulin G (IgG) antibodies against the RBD of the spike protein (anti-RBD) two weeks after first and second doses. Our secondary endpoints were solicited specific local or systemic adverse events within 7 days after the receipt of each dose of the vaccine. There was no difference in the primary outcome between the two vaccine platforms in patients who received two vaccine doses. Unresponsiveness was mainly linked to diabetes. The rate of response after the first dose among younger older patients was significantly larger; however, after the second dose this difference did not persist (p = 0.079). Side effects were similar to those that were observed during the pivotal trials.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Transplante de Órgãos , Humanos , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Imunogenicidade da Vacina , Imunoglobulina G , Imunoglobulina M , Transplante de Órgãos/efeitos adversos , Estudos Prospectivos , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , TransplantadosRESUMO
BACKGROUND: Induction therapy with IL-2 receptor antagonist (IL2-RA) is recommended as a first-line agent in low immunological risk kidney transplant recipients. However, the role of IL2-RA in the setting of tacrolimus-based immunosuppression has not been fully investigated. AIMS: To compare different induction therapeutic strategies with 2 doses of basiliximab vs. no induction in low immunologic risk kidney transplant recipients as per KFSHRC protocol. METHODS: Prospective, randomized, double blind, non-inferiority, controlled clinical trial EXPECTED OUTCOMES: 1. Primary outcomes: Biopsy-proven acute rejection within first year following transplant 2. SECONDARY OUTCOMES: a. Patient and graft survival at 1 year b. eGFR at 6 months and at 12 months c. Emergence of de novo donor-specific antibodies (DSAs) TRIAL REGISTRATION: The study has been prospectively registered at clinicaltrials.gov (NTC: 04404127). Registered on 27 May 2020.
Assuntos
Transplante de Rim , Basiliximab , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , TacrolimoRESUMO
Primary focal segmental glomerulosclerosis recurrence occurs in 10% to 50% of recipients after kidney transplant and may affect both children and adults. Treatment after recurrence with plasma exchange and immunosuppression is quite variable and challenging, and those who do not respond usually progress to allograft failure. Podocyte injury and B7-1 expression and subsequently its blockade (abatacept) have been reported to be associated with complete remission of proteinuria in 4 patients with focal segmental glomerulosclerosis recurrence after kidney transplantation and in 1 patient with focal segmental glomerulosclerosis in native kidney. Here, we report our experience of successfully treating 3 consecutive patients with focal segmental glomerulosclerosis recurrence after kidney transplant with abatacept, which induced proteinuria remission.
Assuntos
Abatacepte/uso terapêutico , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/diagnóstico , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
Although the outcomes of ABO-incompatible (ABOi) kidney transplant recipients are quite favorable, these patients are at increased risk of early antibody-mediated rejection (AMR) and graft loss. Some studies have also shown high mortality in the ABOi group mainly due to increased risk of infections. The AMR rates have been reported anywhere from <10% to >50% in the literature. The outcomes of the ABOi kidney transplants in the Saudi population are not known. In this study, we aimed to determine the graft and patient survival in ABOi kidney transplant recipients in the Saudi population. We included all adult patients who underwent ABOi transplantation between 2007 and 2016. All patients received rituximab, therapeutic plasma exchange, thymoglobulin, intravenous antibiotics, and intravenous immunoglobulin. The maintenance immunosuppression was prednisone, mycophenolate mofetil, and tacrolimus. The data were collected from a prospectively maintained database. A total of 77 patients were included in the study. The most common blood group mismatch was A to O (44.2%), followed by B to O (26.0%) and A to B (16.9%). In the 1st year, 17% of patients developed acute cellular rejection and AMR occurred in 7.8% of patients. Two patients were diagnosed with BK nephropathy. In the 1st year, urinary tract infection occurred in 25 (32.5%) patients. No patient was diagnosed severe viral or fungal infection. In the 1st year, four grafts were lost (graft survival of 94.8%); all grafts were lost within two weeks, three due to AMR and one due to technical reason. One year patient survival was 100%. In this study of ABOi kidney transplant recipients, we observed low risks of infectious complications with excellent patient and graft survival. Our immunosuppressive protocol can be considered safe.
Assuntos
Sistema ABO de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Histocompatibilidade , Imunossupressores/uso terapêutico , Transplante de Rim , Adulto , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Infecções Oportunistas/imunologia , Fatores de Risco , Arábia Saudita , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Donor-specific antibodies (DSA) in sera of sensitized transplant patients are often produced against the specific epitopes on mismatched HLA antigens. In this study, we selected sera from 30 kidney transplant patients with DSA and AMR to define DQ epitopes. Using adsorption and elution assays, we identified 18 antibody reaction patterns to define 6 new epitopes and to confirm 12 previously defined epitopes. In one patient case, one mismatched antigen produced 3 different antibodies and, in another, antibodies were produced against the alpha and beta chains of the same antigen. For some sera, a single epitope can explain reactions for 27 of the 29 DQ beads in the single antigen panel. Several studies highlighted the prevalence of anti-DQ antibodies. In 2011, Almeshari et al. observed DQ DSA in 34/46 (74%) of rejection episodes - 44 patients had DSA and 20 lost their graft due to AMR. Other studies have shown a high prevalence of anti-DQ antibodies and an association with adverse effects on the graft. We conclude that analysis of the epitopes of the DQ antibodies using Adsorption/Elution and testing on single antigen DQ beads helps to better understand the specificities and cross-reactions of DQ antibodies in transplant patients.
Assuntos
Epitopos de Linfócito B/imunologia , Rejeição de Enxerto/imunologia , Cadeias alfa de HLA-DQ/imunologia , Cadeias beta de HLA-DQ/imunologia , Transplante de Rim , Complicações Pós-Operatórias/imunologia , Citotoxicidade Celular Dependente de Anticorpos/genética , Apresentação de Antígeno , Sítios de Ligação de Anticorpos/genética , Linhagem Celular , Mapeamento de Epitopos , Epitopos de Linfócito B/isolamento & purificação , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Histocompatibilidade , Humanos , Isoanticorpos/sangue , Isoanticorpos/imunologia , Ligação Proteica , Transgenes/genéticaRESUMO
BACKGROUND: Kidney transplantation in allosensitized recipients has recently increased. Studies performing cost analysis of desensitization protocols are scarce. MATERIAL/METHODS: We performed an actual cost comparison between kidney transplantation following desensitization and maintenance hemodialysis. Group A (n=35) consisted of allosensitized recipients who underwent desensitization using immunoadsorption and/or plasmapheresis, intravenous immunoglobulin and anti-CD20 antibody who were followed for ≥ 2 years. Group B (n=49) consisted of matched patients who remained on hemodialysis throughout the study period. Actual costs of donor care, surgical procedures, out-patient visits, in-hospital admissions, medications, hemodialysis, immunoadsorption, plasmapheresis, and laboratory and radiology investigations were calculated. Health care services were provided by a single institution. RESULTS: Mortality rate was similar between both groups. The average 4-year actual total cost was $210,779 in group A and $317,186.3 in group B; respectively (p=0.017). Average total cost per patient in group A was $186,608; $14,233; $5,536; $4,402 in the first, second, third and fourth years after transplantation respectively while the average total annual cost per patient in group B was $79,296. The total cost in both groups became equal by month 31. The predicted annual cost savings in group A after 31 months was $33,943. CONCLUSIONS: Despite using costly desensitization protocols, kidney transplantation in sensitized patients provides long-term cost savings compared to maintenance hemodialysis.