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1.
Transpl Int ; 36: 10816, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36819125

RESUMO

The choice between Basiliximab (BSX) or Anti-Thymocyte Globulin (ATG) as induction therapy in non-immunized kidney transplant recipients remains uncertain. Whilst ATG may allow steroid withdrawal and a decrease in tacrolimus, it also increases infectious complications. We investigated outcomes in non-immunized patients receiving a very low dosage of ATG versus BSX as induction. Study outcomes were patient/graft survival, cumulative probabilities of biopsy proven acute rejection (BPAR), infectious episode including CMV and post-transplant diabetes (PTD). Cox, logistic or linear statistical models were used depending on the studied outcome and models were weighted on propensity scores. 100 patients received ATG (mean total dose of 2.0 mg/kg) and 83 received BSX. Maintenance therapy was comparable. Patient and graft survival did not differ between groups, nor did infectious complications. There was a trend for a higher occurrence of a first BPAR in the BSX group (HR at 1.92; 95%CI: [0.77; 4.78]; p = 0.15) with a significantly higher BPAR episodes (17% vs 7.3%, p = 0.01). PTD occurrence was significantly higher in the BSX group (HR at 2.44; 95%CI: [1.09; 5.46]; p = 0.03). Induction with a very low dose of ATG in non-immunized recipients was safe and associated with a lower rate of BPAR and PTD without increasing infectious complications.


Assuntos
Soro Antilinfocitário , Transplante de Rim , Humanos , Basiliximab , Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Rejeição de Enxerto , Sobrevivência de Enxerto , Transplantados
2.
Transpl Int ; 36: 11950, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38213551

RESUMO

In islet transplantation (ITx), primary graft function (PGF) or beta cell function measured early after last infusion is closely associated with long term clinical outcomes. We investigated the association between PGF and 5 year insulin independence rate in ITx and pancreas transplantation (PTx) recipients. This retrospective multicenter study included type 1 diabetes patients who underwent ITx in Lille and PTx in Nantes from 2000 to 2022. PGF was assessed using the validated Beta2-score and compared to normoglycemic control subjects. Subsequently, the 5 year insulin independence rates, as predicted by a validated PGF-based model, were compared to the actual rates observed in ITx and PTx patients. The study enrolled 39 ITx (23 ITA, 16 IAK), 209 PTx recipients (23 PTA, 14 PAK, 172 SPK), and 56 normoglycemic controls. Mean[SD] PGF was lower after ITx (ITA 22.3[5.2], IAK 24.8[6.4], than after PTx (PTA 38.9[15.3], PAK 36.8[9.0], SPK 38.7[10.5]), and lower than mean beta-cell function measured in normoglycemic control: 36.6[4.3]. The insulin independence rates observed at 5 years after PTA and PAK aligned with PGF predictions, and was higher after SPK. Our results indicate a similar relation between PGF and 5 year insulin independence in ITx and solitary PTx, shedding new light on long-term transplantation outcomes.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Transplante de Pâncreas , Humanos , Diabetes Mellitus Tipo 1/cirurgia , Estudos Retrospectivos , Estudos de Coortes , Insulina/uso terapêutico , Transplante de Pâncreas/métodos , Pâncreas , Sobrevivência de Enxerto
3.
J Am Soc Nephrol ; 33(12): 2211-2231, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36280286

RESUMO

BACKGROUND: The mechanisms regulating CD8+ T cell migration to nonlymphoid tissue during inflammation have not been fully elucidated, and the migratory properties of effector memory CD8+ T cells that re-express CD45RA (TEMRA CD8+ T cells) remain unclear, despite their roles in autoimmune diseases and allotransplant rejection. METHODS: We used single-cell proteomic profiling and functional testing of CD8+ T cell subsets to characterize their effector functions and migratory properties in healthy volunteers and kidney transplant recipients with stable or humoral rejection. RESULTS: We showed that humoral rejection of a kidney allograft is associated with an accumulation of cytolytic TEMRA CD8+ T cells in blood and kidney graft biopsies. TEMRA CD8+ T cells from kidney transplant recipients exhibited enhanced migratory properties compared with effector memory (EM) CD8+ T cells, with enhanced adhesion to activated endothelium and transmigration in response to the chemokine CXCL12. CXCL12 directly triggers a purinergic P2×4 receptor-dependent proinflammatory response of TEMRA CD8+ T cells from transplant recipients. The stimulation with IL-15 promotes the CXCL12-induced migration of TEMRA and EM CD8+ T cells and promotes the generation of functional PSGL1, which interacts with the cell adhesion molecule P-selectin and adhesion of these cells to activated endothelium. Although disruption of the interaction between functional PSGL1 and P-selectin prevents the adhesion and transmigration of both TEMRA and EM CD8+ T cells, targeting VLA-4 or LFA-1 (integrins involved in T cell migration) specifically inhibited the migration of TEMRA CD8+ T cells from kidney transplant recipients. CONCLUSIONS: Our findings highlight the active role of TEMRA CD8+ T cells in humoral transplant rejection and suggest that kidney transplant recipients may benefit from therapeutics targeting these cells.


Assuntos
Linfócitos T CD8-Positivos , Transplante de Rim , Humanos , Transplantados , Selectina-P/metabolismo , Receptores Purinérgicos P2X4/metabolismo , Rejeição de Enxerto , Memória Imunológica , Proteômica , Antígenos Comuns de Leucócito/metabolismo , Subpopulações de Linfócitos T/metabolismo
4.
Int J Mol Sci ; 24(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36902067

RESUMO

The pancreas is very susceptible to ischemia-reperfusion injury. Early graft losses due to pancreatitis and thrombosis represent a major issue after pancreas transplantation. Sterile inflammation during organ procurement (during brain death and ischemia-reperfusion) and after transplantation affects organ outcomes. Sterile inflammation of the pancreas linked to ischemia-reperfusion injury involves the activation of innate immune cell subsets such as macrophages and neutrophils, following tissue damage and release of damage-associated molecular patterns and pro-inflammatory cytokines. Macrophages and neutrophils favor tissue invasion by other immune cells, have deleterious effects or functions, and promote tissue fibrosis. However, some innate cell subsets may promote tissue repair. This outburst of sterile inflammation promotes adaptive immunity activation via antigen exposure and activation of antigen-presenting cells. Better controlling sterile inflammation during pancreas preservation and after transplantation is of utmost interest in order to decrease early allograft loss (in particular thrombosis) and increase long-term allograft survival. In this regard, perfusion techniques that are currently being implemented represent a promising tool to decrease global inflammation and modulate the immune response.


Assuntos
Transplante de Rim , Pancreatite , Traumatismo por Reperfusão , Humanos , Inflamação , Pâncreas
5.
Int J Mol Sci ; 23(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36233315

RESUMO

While most viral infections cause mild symptoms and a spontaneous favorable resolution, some can lead to severe or protracted manifestations, specifically in immunocompromised hosts. Kidney injuries related to viral infections may have multiple causes related to the infection severity, drug toxicity or direct or indirect viral-associated nephropathy. We review here the described virus-associated nephropathies in order to guide diagnosis strategies and treatments in cases of acute kidney injury (AKI) occurring concomitantly with a viral infection. The occurrence of virus-associated nephropathy depends on multiple factors: the local epidemiology of the virus, its ability to infect renal cells and the patient's underlying immune response, which varies with the state of immunosuppression. Clear comprehension of pathophysiological mechanisms associated with a summary of described direct and indirect injuries should help physicians to diagnose and treat viral associated nephropathies.


Assuntos
Injúria Renal Aguda , Transplante de Rim , Viroses , Injúria Renal Aguda/etiologia , Humanos , Terapia de Imunossupressão , Rim , Viroses/complicações
6.
Am J Transplant ; 21(3): 1295-1303, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33259686

RESUMO

There are no studies which have compared the risk of severe COVID-19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID-19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single-center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID-19 or mortality. Severe COVID-19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30-day cumulative incidence of severe COVID-19 did not differ between KTR and nontransplant patients; however, 30-day COVID-19-related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C-reactive protein (CRP) were associated with severe COVID-19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID-19-related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID-19-related mortality compared to nontransplant hospitalized patients.


Assuntos
COVID-19/diagnóstico , Rejeição de Enxerto/epidemiologia , Transplante de Rim , Pandemias , Pontuação de Propensão , Sistema de Registros , Transplantados/estatística & dados numéricos , Idoso , COVID-19/epidemiologia , Comorbidade , Feminino , França/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Incidência , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença
7.
Transpl Int ; 34(5): 942-953, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33733553

RESUMO

Since the beginning of our pancreas transplant programme, plasma C-peptide was routinely measured daily during the postoperative period. We aimed to evaluate the clinical interest of the C-peptide in the follow-up of pancreas transplantation with a particular look on early graft failure. From 2000 to 2016, 384 pancreas transplantations were evaluated. We collected and compared C-peptide, glycaemia and adjusted C-peptide (aCP; calculated based on C-peptide, glycaemia and creatininaemia) in patients with and without pancreas failure within 30 days after surgery. Variations of glycaemia, C-peptide and aCP between the day before and the day of failure were also recorded. The difference of aCP was significant during the first week after transplantation between patients with thrombosis and those with functional allograft: 63.2 vs. 26.7 on day 1, P = 0.0003; 61.4 vs. 26.7 on day 3, P < 0.0001; 64.8 vs. 5.7 on day 7, P < 0.0001, respectively. Glycaemia had a median increase of 8% on the day of failure, whereas C-peptide and aCP had, respectively, a median decrease of 88% and 83%. C-peptide monitoring after pancreas transplantation may help to identify graft function and early failure. This sensitive biomarker could allow pre-emptive diagnosis of an early thrombotic event allowing the possibility of rescue interventions.


Assuntos
Transplante de Pâncreas , Trombose , Peptídeo C , Sobrevivência de Enxerto , Humanos , Transplante de Pâncreas/efeitos adversos , Período Pós-Operatório , Estudos Retrospectivos , Trombose/etiologia , Transplante Homólogo
8.
Transpl Infect Dis ; 23(1): e13465, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32939955

RESUMO

Kidney transplant recipients have been supposed vulnerable to severe Covid-19 infection, due to their comorbidities and immunosuppressive therapies. Mild-term complications of Covid-19 are currently unknown, especially in this population. Herein, we report two cases of BKV replication after non-severe SARS-CoV-2 infection. The first case was a 59-year-old man, transplanted 3 months ago, with recent history of slight BKV viremia (3.3 log10 DNA copies/ml). Despite strong reduction of maintenance immunosuppression (interruption of mycophenolic acid and important decrease of calcineurin inhibitors), BKV replication largely increased after Covid-19 and viremia persisted at 4.5 log copy/ml few months later. The second case was a 53-year-old woman, transplanted 15 years ago. She had a recent history of BKV cystitis, which resolved with a decrease of MPA dosage. Few weeks after SARS-CoV-2 infection, she presented recurrence of lower urinary tract symptoms. Our reports highlight that SARS-CoV-2 infection, even without severity, could disrupt immune system and particularly lymphocytes, thus leading to viral replication. Monitoring of viral replications after Covid-19 in kidney transplant recipients could permit to confirm these preliminary observations.


Assuntos
Vírus BK , COVID-19 , Transplante de Rim , Infecções por Polyomavirus/virologia , SARS-CoV-2 , Infecções Tumorais por Vírus/virologia , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Transplantados , Viremia
9.
Kidney Int ; 98(6): 1549-1558, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32853631

RESUMO

Notwithstanding the ongoing coronavirus disease-2019 (Covid-19) pandemic, information on its clinical presentation and prognosis in recipients of a kidney transplant remain scanty. The aim of this registry-based observational study was to explore characteristics and clinical outcomes of recipients of kidney transplants included in the French nationwide Registry of Solid Organ Transplant Recipients with Covid-19. Covid-19 was diagnosed in symptomatic patients who had a positive PCR assay for SARS-CoV-2 or having typical lung lesions on imaging. Clinical and laboratory characteristics, management of immunosuppression, treatment for Covid-19, and clinical outcomes (hospitalization, admission to intensive care unit, mechanical ventilation, or death) were recorded. Risk factors for severe disease or death were determined. Of the 279 patients, 243 were admitted to hospital and 36 were managed at home. The median age of hospitalized patients was 61.6 years; most had comorbidities (hypertension, 90.1%; overweight, 63.8%; diabetes, 41.3%; cardiovascular disease, 36.2%). Fever, cough, dyspnea, and diarrhea were the most common symptoms on admission. Laboratory findings revealed mild inflammation frequently accompanied by lymphopenia. Immunosuppressive drugs were generally withdrawn (calcineurin inhibitors: 28.7%; antimetabolites: 70.8%). Treatment was mainly based on hydroxychloroquine (24.7%), antiviral drugs (7.8%), and tocilizumab (5.3%). Severe Covid-19 occurred in 106 patients (46%). Forty-three hospitalized patients died (30-day mortality 22.8%). Multivariable analysis identified overweight, fever, and dyspnea as independent risk factors for severe disease, whereas age over 60 years, cardiovascular disease, and dyspnea were independently associated with mortality. Thus, Covid-19 in recipients of kidney transplants portends a high mortality rate. Proper management of immunosuppression and tailored treatment of this population remain challenging.


Assuntos
COVID-19/mortalidade , Transplante de Rim/mortalidade , Complicações Pós-Operatórias/mortalidade , Sistema de Registros , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , COVID-19/terapia , Desprescrições , Feminino , França/epidemiologia , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Pandemias/estatística & dados numéricos , Complicações Pós-Operatórias/virologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
20.
Transplantation ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867352

RESUMO

The observation decades ago that inflammatory injuries because of an alloimmune response might be present even in the absence of concomitant clinical impairment in allograft function conduced to the later definition of subclinical rejection. Many studies have investigated the different subclinical rejections defined according to the Banff classification (subclinical T cell-mediated rejection and antibody-mediated rejection), overall concluding that these episodes worsened long-term allograft function and survival. These observations led several transplant teams to perform systematic protocolar biopsies to anticipate treatment of rejection episodes and possibly prevent allograft loss. Paradoxically, the invasive characteristics and associated logistics of such procedures paved the way to investigate noninvasive biomarkers (urine and blood) of subclinical rejection. Among them, several research teams proposed a blood gene signature developed from cohort studies, most of which achieved excellent predictive values for the occurrence of subclinical rejection, mainly antibody-mediated rejection. Interestingly, although all identified genes relate to immune subsets and pathways involved in rejection pathophysiology, very few transcripts are shared among these sets of genes, highlighting the heterogenicity of such episodes and the difficult but mandatory need for external validation of such tools. Beyond this, their application and value in clinical practice remain to be definitively demonstrated in both biopsy avoidance and prevention of clinical rejection episodes. Their combination with other biomarkers, either epidemiological or biological, could contribute to a more accurate picture of a patient's risk of rejection and guide clinicians in the follow-up of kidney transplant recipients.

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