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1.
Am J Transplant ; 23(4): 464-474, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36710135

RESUMO

Isolated microvascular inflammation (iMVI) without HLA donor-specific antibodies or C4d deposition in peritubular capillaries remains an enigmatic phenotype that cannot be categorized as antibody-mediated rejection (ABMR) in recent Banff classifications. We included 221 kidney transplant recipients with biopsies with ABMR (n = 73), iMVI (n = 32), and normal (n = 116) diagnoses. We compared peripheral blood leukocyte distribution by flow cytometry and inflammatory infiltrates in kidney transplant biopsies among groups. Flow cytometry showed fewer lymphocytes and total, CD4+, and CD8+ peripheral T cells in iMVI compared with ABMR and normal cases. ABMR and iMVI had fewer total natural Killer (NK) cells but more NKG2A+ NK cells. Immunohistochemistry indicated that ABMR and iMVI had greater CD3+ and CD68+ glomerular infiltration than normal biopsies, whereas CD8+ and TIA1+ cells showed only increased iMVI, suggesting they are cytotoxic T cells. Peritubular capillaries displayed more CD3+, CD56+, TIA1+, and CD68+ cells in both ABMR and iMVI. In contrast, iMVI had less plasma cell infiltration in peritubular capillaries and interstitial aggregates than ABMR. iMVI displayed decreased circulating T and NK cells mirrored by T cell and NK cell infiltration in the renal allograft, similar to ABMR. However, the lesser plasma cell infiltration in iMVI may suggest an antibody-independent underlying stimulus.


Assuntos
Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Rim/patologia , Anticorpos , Inflamação/patologia , Células Matadoras Naturais , Antígenos HLA , Rejeição de Enxerto/patologia
2.
J Immunol ; 207(7): 1882-1890, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470855

RESUMO

Human CMV infection is frequent in kidney transplant recipients (KTR). Pretransplant Ag-specific T cells and adaptive NKG2C+ NK cells associate with reduced incidence of infection in CMV+ KTR. Expansions of adaptive NKG2C+ NK cells were reported in posttransplant CMV-infected KTR. To further explore this issue, NKG2C+ NK, CD8+, and TcRγδ T cells were analyzed pretransplant and at different time points posttransplant for ≥24 mo in a cohort of CMV+ KTR (n = 112), stratified according to CMV viremia detection. In cryopreserved samples from a subgroup (n = 49), adaptive NKG2C+ NK cell markers and T cell subsets were compared after a longer follow-up (median, 56 mo), assessing the frequencies of CMV-specific T cells and viremia at the last time point. Increased proportions of NKG2C+ NK, CD8+, and TcRγδ T cells were detected along posttransplant evolution in viremia(+) KTR. However, the individual magnitude and kinetics of the NKG2C+ NK response was variable and only exceptionally detected among viremia(-) KTR, presumably reflecting subclinical viral replication events. NKG2C+ expansions were independent of KLRC2 zygosity and associated with higher viral loads at diagnosis; no relation with other clinical parameters was perceived. Increased proportions of adaptive NKG2C+ NK cells (CD57+, ILT2+, FcεRIγ-) were observed after resolution of viremia long-term posttransplant, coinciding with increased CD8+ and Vδ2- γδ T cells; at that stage CMV-specific T cells were comparable to viremia(-) cases. These data suggest that adaptive NKG2C+ NK cells participate with T cells to restore CMV replication control, although their relative contribution cannot be discerned.


Assuntos
Infecções por Citomegalovirus/imunologia , Rejeição de Enxerto/imunologia , Transplante de Rim , Células Matadoras Naturais/imunologia , Muromegalovirus/fisiologia , Imunidade Adaptativa , Idoso , Idoso de 80 Anos ou mais , Feminino , Interações Hospedeiro-Patógeno , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo
3.
BMC Nurs ; 22(1): 44, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36797711

RESUMO

BACKGROUND: Waiting time for kidney transplants (KT) is an important health determinant for patients with chronic kidney disease (CKD). During this time, ongoing evaluation and participation is necessary in order to guarantee the quality and suitability of the proposed treatment. There is no existing literature on the potential impact of inclusion of an Advanced Practice Nurse (APN) role in the hospital setting on care for CKD patients who are candidates for KT. The main objectives of this protocol are: to analyse outpatient nursing activity in the care of individuals with KT in Spain; to identify the needs of individuals who are KT candidates; and to measure the impact of the APN role through patient outcomes and experiences. These objectives are fulfilled through 5 specific related substudies. METHODS: A convergent parallel mixed methods approach will be conducted between July 2021 and April 2024. Quantitative and qualitative data will be collected and analysed separately to ascertain whether the findings confirm or contradict one another. Each of the 5 substudies of the project require a specific design, sampling method, and data collection procedure in order to meet the overall objectives for the project. DISCUSSION: The results of the project are expected to inform the design of future nursing roles and contribute to future improvements in the quality of care provided. The data that may be obtained from this protocol are limited to the specific context of the study facility and may be extrapolated but not compared to other settings due to the variability of care pathways for KT candidates internationally. TRIAL REGISTRATION: This project was approved by the Clinical Research Ethics Committee (no.2020/9418/I). The study was supported by the "Strategic Plan for Health Research and Innovation" from the Generalitat de Catalunya, registration number SLT017/20/000001, with a contribution of 57,239 euros.

4.
Clin Infect Dis ; 74(5): 757-765, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-34228099

RESUMO

BACKGROUND: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. Our aim was to determine whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy. METHODS: In this open-label, noninferiority clinical trial, patients were randomized 1:1 to follow an immunoguided strategy, receiving prophylaxis until CMV-CMI recovery or to receive fixed-duration prophylaxis until day 90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed 2 deleterious events (CMV disease/replication and neutropenia). RESULTS: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs 2.7%; P = .149) and replication (17.1% vs 13.5%; log-rank test, P = .422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs 37.8%; odds ratio, 6.0; P < .001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome. CONCLUSIONS: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed. CLINICAL TRIALS REGISTRATION: NCT03123627.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Soro Antilinfocitário/uso terapêutico , Antivirais/uso terapêutico , Citomegalovirus , Ganciclovir/uso terapêutico , Humanos , Transplante de Rim/efeitos adversos , Transplantados
5.
Am J Transplant ; 22(3): 786-800, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34551187

RESUMO

Studies are urgently needed to characterize immunogenicity, efficacy, and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in kidney transplant (KT) recipients, excluded from major clinical trials. Complex ELISPOT and other cellular response techniques have been applied, but simpler tools are needed. An easy-to-use real-world monitoring of SARS-CoV-2 IgG antibodies against the Spike protein and QuantiFERON® SARS-CoV-2 IFNγ release assay (IGRA) were performed at baseline and 28 days after the second dose in KT recipients and controls (dialysis patients and healthy ones). All healthy controls and >95% dialysis controls became positive for anti-S IgG antibodies, while only 63.3% of KT patients seroconverted with a very low antibody level. A positive IGRA was documented in 96.9% of controls, 89.3% peritoneal dialysis, 77.6% hemodialysis, 61.3% of KT patients transplanted more than 1 year ago and only 36% of those transplanted within the previous 12 months. Overall, 100% of healthy controls, 95.4% of dialysis patients and 78.8% KT recipients developed any immune response (humoral and/or cellular) against SARS-CoV-2. KT patients showed low rates of immune responses to mRNA Coronavirus infectious disease 2019 vaccines, especially those with recent transplantations. Simple humoral and cellular monitoring is advisable, so that repeated doses may be scheduled according to the results.


Assuntos
COVID-19 , Transplante de Rim , Aloenxertos , Anticorpos Antivirais , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade , Testes de Liberação de Interferon-gama , Transplante de Rim/efeitos adversos , RNA Mensageiro/genética , Diálise Renal , SARS-CoV-2
6.
J Infect Dis ; 223(7): 1205-1213, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32779713

RESUMO

BACKGROUND: This is a prospective, multicenter, observational study in cytomegalovirus (CMV)-seropositive kidney transplant recipients with pretransplant CMV-specific cell-mediated immunity (CMV-CMI) receiving antithymocyte globulin (ATG). We aimed to investigate posttransplant CMV-CMI over time and the impact of the dose-dependent ATG. METHODS: CMV-CMI was assessed at days +30, +45, +60, and +90 after transplantation with the QuantiFERON-CMV assay. A reactive result (interferon-γ [IFN-γ] ≥ 0.2 IU/mL) indicated a positive CMV-CMI. RESULTS: A total of 78 positive CMV-CMI patients were enrolled in the study, of which 59.5% had a positive CMV-CMI at day +30 and 82.7% at day +90. Multivariate logistic regression analysis showed that ATG dose was not associated with positive CMV-CMI at any point. However, pretransplant IFN-γ level (>12 IU/mL vs ≤12 IU/mL) was associated with positive CMV-CMI at day +30 (odds ratio, 12.9; 95% confidence interval, 3.1-53.3; P < .001). In addition, all the patients who did not recover CMV-CMI at day +90 had a pretransplant IFN-γ level ≤12 IU/mL. CONCLUSIONS: More than half of CMV-seropositive kidney transplant recipients receiving ATG recover (or maintain) CMV-CMI by the first month after transplantation. The pretransplant IFN-γ level, but not the ATG dose, shows a strong association with the kinetics of this recovery.


Assuntos
Soro Antilinfocitário/uso terapêutico , Antivirais , Infecções por Citomegalovirus , Imunidade Celular , Transplante de Rim , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Humanos , Interferon gama/análise , Estudos Prospectivos , Linfócitos T
7.
Am J Transplant ; 20(3): 663-676, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31612635

RESUMO

Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV-specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D-R-) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell-associated markers (ie, NKG2A, CD57, Immunoglobulin-like transcript 2 [LIR1 or LILRB1], FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan-Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV-specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Citomegalovirus , Humanos , Transplante de Rim/efeitos adversos , Células Matadoras Naturais , Leucócitos Mononucleares
8.
Am J Transplant ; 20(10): 2883-2889, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32471001

RESUMO

The SARS-Cov-2 infection disease (COVID-19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed COVID-19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti-retroviral and tocilizumab. Short-term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D-dimer, C-reactive protein, and IL-6 at their first tests. COVID-19 is frequent among the elderly KT population and associates a very early and high mortality rate.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Transmissão de Doença Infecciosa/estatística & dados numéricos , Rejeição de Enxerto/prevenção & controle , Transplante de Rim , Pneumonia Viral/epidemiologia , Medição de Risco/métodos , Transplantados/estatística & dados numéricos , Idoso , COVID-19 , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Hospitalização/tendências , Humanos , Incidência , Masculino , Pandemias , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Espanha/epidemiologia , Fatores de Tempo
9.
Am J Transplant ; 20(11): 3182-3190, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32654422

RESUMO

Acute respiratory distress syndrome associated with coronavirus infection is related to a cytokine storm with large interleukin-6 (IL-6) release. The IL-6-receptor blocker tocilizumab may control the aberrant host immune response in patients with coronavirus disease 2019 (COVID-19) . In this pandemic, kidney transplant (KT) recipients are a high-risk population for severe infection and showed poor outcomes. We present a multicenter cohort study of 80 KT patients with severe COVID-19 treated with tocilizumab during hospital admission. High mortality rate was identified (32.5%), related with older age (hazard ratio [HR] 3.12 for those older than 60 years, P = .039). IL-6 and other inflammatory markers, including lactic acid dehydrogenase, ferritin, and D-dimer increased early after tocilizumab administration and their values were higher in nonsurvivors. Instead, C-reactive protein (CRP) levels decreased after tocilizumab, and this decrease positively correlated with survival (mean 12.3 mg/L in survivors vs. 33 mg/L in nonsurvivors). Each mg/L of CRP soon after tocilizumab increased the risk of death by 1% (HR 1.01 [confidence interval 1.004-1.024], P = .003). Although patients who died presented with worse respiratory situation at admission, this was not significantly different at tocilizumab administration and did not have an impact on outcome in the multivariate analysis. Tocilizumab may be effective in controlling cytokine storm in COVID-19 but randomized trials are needed.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/epidemiologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim , Pandemias , SARS-CoV-2 , Adulto , Comorbidade , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Resultado do Tratamento , Adulto Jovem
10.
Transpl Int ; 33(9): 1071-1077, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32418259

RESUMO

Delayed graft function (DGF) is associated with poorer graft survival and higher rate of acute rejection (AR). It is unknown whether this negative influence relies on the increased risk of AR or the DGF itself. The different Kidney Donor Profile Index (KDPI) values may also play a role in this interaction. Retrospective study aimed to evaluate the impact of DGF on graft function and graft survival in a subset of KT recipients (2004-2017). We also analyzed the relationship between KDPI and DGF. The study includes 601 KT, 226 of them (37%) developed DGF. Graft survival was lower in patients with DGF compared with non-DGF patients. Multivariable analysis revealed DGF as risk factor for graft loss, independently of the presence or not of acute rejection. Between DGF patients, we observed poorer graft survival in patients with higher KDPI value (>85%). We observed a trend of a greater impact of KDPI in patients with DGF, although this interaction was not statistically significant. Additionally, we observed poorer 12-month graft function in DGF patients. DGF is related to poorer graft survival independently of the developed acute rejection. This negative impact might be influenced by high KDPI values.


Assuntos
Transplante de Rim , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos
11.
Kidney Blood Press Res ; 45(5): 768-774, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32898845

RESUMO

INTRODUCTION: Chronic kidney disease (CKD) increases the risk of mortality during coronavirus disease 2019 (COVID-19) episodes, and some reports have underlined the high incidence and severity of this infection in dialysis patients. Information on COVID-19 in nondialysis CKD patients is not available yet. CASE REPORTS: Here we present 7 patients with grade 4-5 CKD who developed symptomatic COVID-19; they comprise 2.6% of our 267 advanced CKD patients. The estimated GFR was between 12 and 20 mL/min during the month prior to COVID-19. The 3 major symptoms were fever, cough, and dyspnea, and 5 patients showed bilateral pneumonia. Hydroxychloroquine, azithromycin, ceftriaxone, and steroids were the most frequently prescribed drugs. Two patients needed noninvasive mechanical ventilation. All patients showed minimal to moderate kidney function deterioration during admission, with an eGFR decline below 5 mL/min in 6 cases. No patient required acute dialysis. Six patients were discharged alive and remained dialysis free athe t the time of reporting, and one 76-year-old patient died. CONCLUSIONS: COVID-19 affects grade 4-5 CKD patients, but prognosis may be acceptable if prompt supportive measures are applied. These findings should be confirmed in larger cohorts, and further observations will be needed to understand the full spectrum of clinical features and the optimal approach to COVID-19 in patients with advanced CKD.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Insuficiência Renal Crônica/diagnóstico por imagem , Índice de Gravidade de Doença , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Infecções por Coronavirus/complicações , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Insuficiência Renal Crônica/complicações , SARS-CoV-2
13.
J Immunol ; 198(1): 94-101, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-27913630

RESUMO

CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C+ NK cells. The distribution of NKG2C+ NK cells and NKG2C genotypes (NKG2C+/+, NKG2C+/del, NKG2Cdel/del) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts. Assessment of CMV viremia was restricted to symptomatic cases in the retrospective study, but was regularly monitored in the prospective cohort. Overall, the proportions of NKG2C+ NK cells were significantly higher in KTRs who had suffered posttransplant symptomatic CMV infection in the cross-sectional study. Yet, along the prospective follow-up (3, 6, 12, and 24 mo), posttransplant NKG2C+ NK cell expansions were not observed in every patient with detectable viremia who received preemptive antiviral therapy, suggesting that the adaptive NK cell response may be inversely related with the degree of CMV control. Remarkably, the incidence of posttransplant viremia was reduced among cases with high pretransplant levels of NKG2C+ NK cells. The NKG2C genotype distribution was comparable in KTR and healthy controls, and greater proportions of NKG2C+ cells were detected in NKG2C+/+ than in NKG2C+/del patients. Yet, a trend toward increased NKG2C+/del and reduced NKG2C+/+ frequencies associated with symptomatic infection was appreciated in both cohorts. Altogether, our results indirectly support that adaptive NKG2C+ NK cells are involved in the control of CMV in KTRs.


Assuntos
Infecções por Citomegalovirus/imunologia , Transplante de Rim/efeitos adversos , Células Matadoras Naturais/imunologia , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Imunidade Adaptativa/imunologia , Adulto , Estudos de Coortes , Estudos Transversais , Infecções por Citomegalovirus/epidemiologia , Feminino , Citometria de Fluxo , Seguimentos , Genótipo , Humanos , Hospedeiro Imunocomprometido , Imunofenotipagem , Incidência , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/genética , Viremia/epidemiologia , Viremia/imunologia
14.
Am J Transplant ; 18(4): 927-935, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28949089

RESUMO

There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo-controlled, double-blind clinical trial to evaluate efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010-023746-67). Patients with transplant glomerulopathy and anti-HLA donor-specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m2 ) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012-2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (-4.2 ± 14.4 vs. -6.6 ± 12.0 mL/min per 1.73 m2 , P-value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P-value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA.


Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunoglobulinas Intravenosas/administração & dosagem , Isoanticorpos/efeitos adversos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Rituximab/administração & dosagem , Adulto , Aloenxertos , Doença Crônica , Método Duplo-Cego , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Fatores Imunológicos/administração & dosagem , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Fatores de Risco , Doadores de Tecidos
15.
Transpl Int ; 31(8): 838-860, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29582474

RESUMO

The objective of this review was to assess whether dual kidney transplantation (DKT) is better than single KT (SKT) for optimizing the use of expanded criteria donor kidneys. We did a systematic literature search and meta-analyses when possible, pooling data for calculating relative risks (RR) of major outcomes. Twenty-five studies met the inclusion criteria. One-year serum creatinine was better after DKT vs. SKT (mean difference -0.27 [-0.37, -0.17], P < 0.001), with less incidence of acute rejection (RR 0.66 [0.52, 0.85], P < 0.001) and without differences at five years. Less DGF was seen in DKT (RR 0.88 [0.76, 1.02], P = 0.09). Mortality at 1 and 3 years was similar after dual or SKT, but mortality at five years was lower after DKT (RR 0.71 [0.53, 0.94], P = 0.02). One-year graft loss was similar between dual (n = 4158) and SKT (n = 51 800) (RR 0.97 [0.87, 1.09], P = 0.62). Three- and five-year graft loss was not considered because of high heterogeneity between studies. In conclusion, short-term graft function and long-term patient survival are better in recipients receiving DKT vs. SKT. However, these differences are based on few retrospective reports with a relatively low number of cases. Good quality randomized controlled trials are needed to assess whether the investment of two kidneys in one recipient is justified in face of the current organ shortage.


Assuntos
Seleção do Doador/normas , Transplante de Rim , Humanos , Testes de Função Renal
16.
Kidney Blood Press Res ; 43(5): 1655-1665, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30380547

RESUMO

BACKGROUND AND AIMS: Complement system seems to play an important role in the pathogenesis of Acute Kidney Injury (AKI). The aim of this study was to investigate the role of complement system in the pathogenesis of human AKI. For this purpose, we studied Membrane Attack Complex (MAC) and factor H in plasma and kidney tissue in AKI. METHODS: Plasmatic concentrations of MAC and Factor H were studied in patients with hospital-acquired AKI and their respective controls. MAC and Factor H expression and localization within the kidney were studied by immunohistochemistry in kidney tissue samples from autopsies. Demographical, past medical, and laboratory data in patients on admission and 3 years after discharge were recorded. RESULTS: Plasmatic MAC concentrations were significantly higher in AKI-patients (5848±3604 vs 3703±1483 mAU/mL, p< 0.01), mainly in the severe cases, as measured by the need of renal replacement therapy, non-recovery of renal function, RIFLE classification and CKD development. MAC deposition was observed in tubular epithelial cell basal membranes, showing a larger number of tubules with MAC deposition, larger perimeter of affected tubules and greater intensity of MAC immunostaining in AKI patients. Factor H concentrations were higher in AKI patients (0.86±0.05 vs 0.60±0.04 mg/mL, p=0.007), showing a strong positive association with plasmatic MAC (r=0.7, p< 0.01)). Factor H immunostaining showed a tubular cytoplasmic pattern, with significant variations in the staining intensity, associated with the severity of histologic damage. CONCLUSION: Our data confirm that complement system is involved in human AKI, through the lytic action of MAC in tubular epithelial cells. These results suggest that complement system activation in AKI could be related with CKD development.


Assuntos
Injúria Renal Aguda/etiologia , Complexo de Ataque à Membrana do Sistema Complemento/análise , Injúria Renal Aguda/terapia , Idoso , Ativação do Complemento , Fator H do Complemento/análise , Células Epiteliais/patologia , Feminino , Humanos , Imuno-Histoquímica , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Terapia de Substituição Renal
17.
Hum Immunol ; 85(2): 110749, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38238229

RESUMO

BACKGROUND: Alloantibodies, especially anti-human leukocyte antigen antibodies (HLA antibodies), and autoantibodies, as angiotensin II type 1 receptor antibodies (AT1R antibodies), may complicate the access and the course of transplantation. Pregnancy is a known source of HLA antibodies, with most studies evaluating pregnancy-induced sensitization by complement-dependent cytotoxicity assays, mainly after childbirth. AT1R antibodies have been evaluated in the context of preeclampsia. We aimed to evaluate pregnancy as a natural source of HLA antibodies and AT1R antibodies, their dynamics along gestation and the potential factors involved in antibody appearance. METHODS: Serum samples from pregnant women were collected during the three trimesters of pregnancy (1T, 2T, 3T). Presence of HLA antibodies was assessed by screening beads on Luminex and AT1R antibodies by ELISA. RESULTS: A cohort of 138 pregnant women were included. Samples from all were tested in 1T, 127 in 2T and 102 in 3T. HLA antibodies increased from 29.7 % (1T) to 38.2 % (3T). AT1R antibodies were stable around 30 % along pregnancy. Up to 43.2 % multiparous women had HLA antibodies, with a similar proportion of class I and class II antibodies. In primiparous women HLA antibodies increased along pregnancy (from 17.6 % to 34.1 %), with predominance of class II HLA antibodies. AT1R antibodies were not different in primiparous and multiparous women. CONCLUSIONS: Pregnancy is a relevant source of HLA antibodies sensitization, but not of AT1R antibodies. HLA antibodies increased clearly in primiparous women with predominance of class II. The use of newer solid-phase techniques on Luminex evidence a higher degree of HLA sensitization during pregnancy.


Assuntos
Transplante de Rim , Humanos , Feminino , Gravidez , Receptor Tipo 1 de Angiotensina , Rejeição de Enxerto , Autoanticorpos , Antígenos HLA
18.
Nurs Open ; 10(10): 6668-6689, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37480193

RESUMO

AIMS: To analyse the aspects involved in the care of individuals assessed as kidney transplant candidates and to identify the role of nurses in providing specialised care for this population. DESIGN: Scoping review. The results were summarised using a narrative synthesis technique. DATA SOURCES: A review of the literature published between 2001 and 2021 was conducted between October and November 2021 using PubMed, CINAHL and SciELO. REVIEW METHODS: The research team agreed on a search strategy based on clinical practice guidelines for assessing kidney transplantation candidates. Quantitative, qualitative and mixed methods studies published in peer-reviewed journals in English, Spanish, French and Portuguese were included. RESULTS: A total of 377 studies were identified, and 49 articles were included after the inclusion and exclusion criteria were applied. The narrative synthesis was structured into four themes: Physical needs; Psychological and quality of life needs; Education and adherence needs; and Nurses' role. CONCLUSION: Nursing assessment of kidney transplantation candidates should encompass physical, psychosocial and adherence aspects. A variety of methodologies and resources are available for this assessment. Nurses contribute to coordinating access to kidney transplantation, aiming to improve adherence to an appropriate lifestyle to prevent patients from being excluded from kidney transplantation or suffering from kidney transplantation-related complications. IMPACT: Based on our findings, we managed to design a nursing care map for kidney transplantation candidates combining the main elements of nursing care that should be incorporated into this process. Advanced practice nursing professionals play a crucial role in accessing renal transplant care.


Assuntos
Prática Avançada de Enfermagem , Transplante de Rim , Cuidados de Enfermagem , Humanos , Qualidade de Vida , Ansiedade
19.
Nefrologia (Engl Ed) ; 43 Suppl 2: 85-90, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36681516

RESUMO

Membranous nephropathy (MN) is a common cause of nephrotic syndrome after kidney transplantation (KT); however, scarce is known regarding post-KT thrombospondin type-1 domain-containing 7A (THSD7A)-positive MN. Herein, we report on a 72-year-old woman with end-stage kidney disease due to chronic interstitial nephritis (1996). In February 2020, she received a second deceased-donor KT, achieving optimal kidney function but presenting early post-KT proteinuria, reaching up to 1800mg/24h six months after transplantation, controlled with renin-angiotensin-aldosterone system (RAAS) blockade. In July 2021, a kidney allograft biopsy revealed features consistent with MN. Immunohistochemical stains showed diffuse and granular THSD7A and C4d deposition in glomerular capillary walls and negative PLA2R and IgG4 staining. No anti-THSD7A antibodies were detected in the serum. The pre-implantation biopsy showed no MN-associated lesions and negative THSD7A staining. Secondary triggers such as malignancy were discarded. The present report illustrates a THSD7A-positive MN in a KT recipient. Despite lacking native kidney biopsy and early presentation, a recurrent MN seemed unprovable due to documented native kidney disease and a long time span between native kidney disease and MN diagnosis. We, therefore, presumed primary de novo disease. Two years after KT, kidney function remains stable, and the patient has reached complete remission of proteinuria.


Assuntos
Glomerulonefrite Membranosa , Transplante de Rim , Feminino , Humanos , Idoso , Glomerulonefrite Membranosa/diagnóstico , Transplante de Rim/efeitos adversos , Trombospondinas , Glomérulos Renais , Proteinúria
20.
Nefrologia (Engl Ed) ; 43(3): 316-327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37507293

RESUMO

INTRODUCTION: The improvement of kidney allograft recipient and graft survival showed a decrease over the last 40 years. Long-term graft loss rate remained stable during a 25-year time span. Knowing the changing causes and the risk factors associated with graft loss requires special attention. The present study aimed to assess the causes of graft loss and kidney allograft recipient death. Also, we aimed to compare two different periods (1979-1999 and 2000-2019) to identify changes in the characteristics of the failed allografts and recipient and donors profile. METHODS AND PATIENTS: We performed a single-center cohort study. We included all the kidney transplant recipients at the Hospital del Mar (Barcelona) between May 1979 and December 2019. Graft loss was defined as recipient death with functioning graft and as loss of graft function (return to dialysis or retransplantation). We assessed the causes of graft loss using clinical and histological information. We also analyzed the results of the two different transplant periods (1979-1999 and 2000-2019). RESULTS: Between 1979 and 2019, 1522 transplants were performed. The median follow-up time was 56 (IQR 8-123) months. During follow-up, 722 (47.5%) grafts were lost: 483 (66.9%) due to graft failure and 239 (33.1%) due to death with functioning graft. The main causes of death were cardiovascular (25.1%), neoplasms (25.1%), and infectious diseases (21.8%). These causes were stable between the two periods of time. Only the unknown cause of death has decreased in the last period. The main cause of graft failure (loss of graft function) was the allograft chronic dysfunction (75%). When histologic information was available, antibody-mediated rejection (ABMR) and interstitial fibrosis/tubular atrophy (IF/TA) were the most frequent specific causes (15.9% and 12.6%). Of the graft failures, 213 (29.5%) were early (<1 year of transplantation). Vascular thrombosis was the main cause of early graft failure in the second period (2000-2019) (46.7%) and T-cell-mediated rejection (TCMR) was the main cause (31.3%) in the first period (1979-1999). The causes of late graft loss were similar between the two periods. CONCLUSIONS: The causes of kidney allograft recipient death are still due to cardiovascular and malignant diseases. Vascular thrombosis has emerged as a frequent cause of early graft loss in the most recent years. The evaluation of the causes of graft loss is necessary to improve kidney transplantation outcomes.


Assuntos
Rejeição de Enxerto , Trombose , Humanos , Estudos de Coortes , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Rim/patologia , Aloenxertos
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