RESUMO
Clinicians have few tools to predict the risk of alloimmune injury that would guide immunosuppression management in renal transplant patients. We evaluated human leukocyte antigen (HLA)-DR/DQ molecular mismatch to predict de novo donor-specific antibodies (DSAs) during the first year of transplant and explored how differences in tacrolimus exposure may modulate this risk. HLA-DR and -DQ eplet mismatches were determined between 444 donor-recipient pairs in Denver, Colorado between 2007 and 2013. Previously defined mismatch thresholds stratified recipients into low- (N = 119), intermediate- (N = 153), and high- (N = 172) risk categories. The area under the curve for DSA at 1 year was 0.84 and 0.82 for HLA-DR and HLA-DQ eplet mismatches, respectively. Compared to low-risk patients, there was a graded increase in risk of DR/DQ DSA in intermediate (HR 15.39, 95% CI 2.01-118.09, p = .009) and high-risk (HR 23.81, 95% CI 3.17-178.66, p = 0.002) categories. Intermediate- and high-risk patients with a mean tacrolimus <6 ng/ml versus >8 ng/ml had increased risk of DR/DQ DSA at 1 year (HR 2.34, 95% CI 1.05-5.22, p = .04). HLA molecular mismatch represents a reproducible, objective, and clinically relevant tool to stratify patients by alloimmune risk and may help guide personalized immunosuppression management.
Assuntos
Rejeição de Enxerto , Tacrolimo , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Antígenos HLA/genética , Antígenos HLA-DR , Teste de Histocompatibilidade , Humanos , Estados UnidosRESUMO
De novo donor-specific antibodies (dnDSAs) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common among immunosuppressive approaches used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSAs has not been established. We evaluated mean TAC C0 (tacrolimus trough concentration) and TAC time in therapeutic range for the risk of dnDSAs in a cohort of 538 patients in the first year after kidney transplantation. A mean TAC C0 < 8 ng/mL was associated with dnDSAs by 6 months (odds ratio [OR] 2.51, 95% confidence interval [CI] 1.32-4.79, P = .005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, P = .004), and there was a graded increase in risk with lower mean TAC C0 . TAC time in the therapeutic range of <60% was associated with dnDSAs (OR 2.05, 95% CI 1.28-3.30, P = .003) and acute rejection (hazard ratio [HR] 4.18, 95% CI 2.31-7.58, P < .001) by 12 months and death-censored graft loss by 5 years (HR 3.12, 95% CI 1.53-6.37, P = .002). TAC minimization may come at a cost of higher rates of dnDSAs, and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes.
Assuntos
Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto/imunologia , Isoanticorpos/sangue , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Tacrolimo/efeitos adversos , Doadores de Tecidos , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Hypertension in renal transplant recipients is common and ranges from 50% to 80% in adult recipients and from 47% to 82% in pediatric recipients. Cardiovascular morbidity and mortality and shortened allograft survival are important consequences of inadequate control of hypertension. In this review, we examine the epidemiology, pathophysiology, and management considerations of post-transplant hypertension. Donor and recipient factors, acute and chronic allograft injury, and immunosuppressive medications may each explain some of the pathophysiology of post-transplant hypertension. As observed in other patient cohorts, renal artery stenosis and adrenal causes of hypertension may be important contributing factors. Notably, BP treatment goals for renal transplant recipients remain an enigma because there are no adequate randomized controlled trials to support a benefit from targeting lower BP levels on graft and patient survival. The potential for drug-drug interactions and altered pharmacokinetics and pharmacodynamics of the different antihypertensive medications need to be carefully considered. To date, no specific antihypertensive medications have been shown to be more effective than others at improving either patient or graft survival. Identifying the underlying pathophysiology and subsequent individualization of treatment goals are important for improving long-term patient and graft outcomes in these patients.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Fatores Etários , Determinação da Pressão Arterial , Criança , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Hipertensão/epidemiologia , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Transplante de Rim/métodos , Masculino , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do TratamentoRESUMO
BACKGROUND: While kidney transplant recipients of African American (AA) descent are frequently considered at increased risk of acute rejection, the value of induction therapy is not defined in settings of lower immunologic risk and modern immunosuppression. METHODS: Using the Scientific Registry of Transplant Recipients database, we identified 23,244 primary kidney transplant recipients with panel-reactive antibody (PRA) = 0% treated with TAC/MPA and prednisone from 2000 to 2008. We compared acute rejection, graft survival (GS), and patient survival rates among AA and non-AA and further stratified by induction therapy (none, IL2ra, or rATG). RESULTS: One-yr acute rejection was higher in AA than in non-AA overall (14.5% vs. 9.9%, hazard ratio [HR] for acute rejection [AR] 1.43, p < 0.0001) and was higher regardless of induction agent use. Induction therapy was associated with a reduction in AR, but no benefit in GS in AA or non-AA. In AA, rATG (adjusted relative risk [RR] 0.81, CI 0.70-0.94) and IL2ra (adjusted RR 0.80, CI 0.68-0.93) were similarly effective in reducing AR rates, but did not reach comparable outcomes as in non-AA. CONCLUSION: African Americans who are at otherwise lower immunologic risk have a higher risk of rejection despite modern immunosuppression. Depleting or non-depleting induction therapy similarly reduces but does not entirely mitigate this increased risk, with no impact on three-yr GS.
Assuntos
Negro ou Afro-Americano/etnologia , Rejeição de Enxerto/etnologia , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/etnologia , Adulto , Etnicidade , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de RiscoRESUMO
Defective control of the alternative pathway of complement is an important risk factor for several renal diseases, including atypical hemolytic uremic syndrome. Infections, drugs, pregnancy, and hemodynamic insults can trigger episodes of atypical hemolytic uremic syndrome in susceptible patients. Although the mechanisms linking these clinical events with disease flares are unknown, recent work has revealed that each of these clinical conditions causes cells to release microparticles. We hypothesized that microparticles released from injured endothelial cells promote intrarenal complement activation. Calcineurin inhibitors cause vascular and renal injury and can trigger hemolytic uremic syndrome. Here, we show that endothelial cells exposed to cyclosporine in vitro and in vivo release microparticles that activate the alternative pathway of complement. Cyclosporine-induced microparticles caused injury to bystander endothelial cells and are associated with complement-mediated injury of the kidneys and vasculature in cyclosporine-treated mice. Cyclosporine-induced microparticles did not bind factor H, an alternative pathway regulatory protein present in plasma, explaining their complement-activating phenotype. Finally, we found that in renal transplant patients, the number of endothelial microparticles in plasma increases 2 weeks after starting tacrolimus, and treatment with tacrolimus associated with increased C3 deposition on endothelial microparticles in the plasma of some patients. These results suggest that injury-associated release of endothelial microparticles is an important mechanism by which systemic insults trigger intravascular complement activation and complement-dependent renal diseases.
Assuntos
Micropartículas Derivadas de Células/efeitos dos fármacos , Ciclosporina/toxicidade , Células Endoteliais/efeitos dos fármacos , Imunossupressores/toxicidade , Animais , Micropartículas Derivadas de Células/metabolismo , Ativação do Complemento/efeitos dos fármacos , Complemento C3/análise , Células Endoteliais/ultraestrutura , Rim/efeitos dos fármacos , Rim/patologia , Transplante de Rim , Masculino , Células Mesangiais/efeitos dos fármacos , Células Mesangiais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Tacrolimo/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Acute kidney injury (AKI) in transplant recipients is a prevalent condition with a broad list of potential inciting causes. This review highlights recent data describing the epidemiology and long-term consequences of transplant AKI, novel interventions in the management of delayed graft function (DGF), and noninvasive diagnostic strategies. RECENT FINDINGS: The incidence and outcomes of nontransplant AKI are well documented, and similar data are emerging in the transplant setting with recent reports suggesting a high incidence rate and significant impact on long-term graft outcomes. DGF represents a 'pure' form of transplant AKI, and many interventional trials aiming to limit ischemia-reperfusion-induced injury have recently been reported or are currently ongoing. The search for accurate noninvasive predictors of DGF and acute rejection is ongoing and recent literature describes novel plasma and urine-based biomarkers as well as transcriptional profiling methods with high potential for clinical applicability. SUMMARY: AKI in transplant recipients is a frequent occurrence with significant potential for poor long-term graft outcomes. Recent efforts to limit ischemia-reperfusion injury and diagnose transplant AKI via noninvasive methods may help to minimize the impact of AKI on future graft function.
Assuntos
Injúria Renal Aguda/etiologia , Transplante de Rim/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/prevenção & controle , Biomarcadores/análise , Função Retardada do Enxerto/diagnóstico , Função Retardada do Enxerto/etiologia , Seleção do Doador , Perfilação da Expressão Gênica , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Coleta de Tecidos e ÓrgãosRESUMO
This study investigated the effect of the coefficient of friction of a running surface on an athlete's sprint time in a sled-towing exercise. The coefficients of friction of four common sports surfaces (a synthetic athletics track, a natural grass rugby pitch, a 3G football pitch, and an artificial grass hockey pitch) were determined from the force required to tow a weighted sled across the surface. Timing gates were then used to measure the 30-m sprint time for six rugby players when towing a sled of varied weight across the surfaces. There were substantial differences between the coefficients of friction for the four surfaces (micro = 0.21-0.58), and in the sled-towing exercise the athlete's 30-m sprint time increased linearly with increasing sled weight. The hockey pitch (which had the lowest coefficient of friction) produced a substantially lower rate of increase in 30-m sprint time, but there were no significant differences between the other surfaces. The results indicate that although an athlete's sprint time in a sled-towing exercise is affected by the coefficient offriction of the surface, the relationship relationship between the athlete's rate of increase in 30-m sprint time and the coefficient of friction is more complex than expected.
Assuntos
Desempenho Atlético , Fricção , Corrida/fisiologia , Adolescente , Adulto , Humanos , Masculino , Poaceae , Equipamentos Esportivos , Propriedades de Superfície , Fatores de Tempo , Adulto JovemRESUMO
Advances in immunosuppressive therapy have drastically improved acute rejection rates in kidney transplant recipients over the past five decades. Nevertheless, it should remain high on any differential diagnosis of unexplained graft dysfunction because of the potential negative effect on graft longevity. Understanding the pre- and post-transplant risk factors for acute rejection can help estimate the probability of immunologic graft damage, and accurate identification of the type and severity of acute rejection will guide appropriate treatment. Tissue biopsy remains the gold standard for evaluating immunologic graft damage, and the histologic definition of acute rejection has evolved in recent years. Intravenous steroids and T cell depletion remain the standard therapy for T cell-mediated rejection and are effective in reversing most cases. Plasma exchange and intravenous Ig, with or without rituximab, are most commonly used for the treatment of antibody-mediated rejection and several newer agents have recently been investigated for severe cases. This review aims to provide the general nephrologist caring for transplant recipients with an approach to immunologic risk assessment and a summary of recent advances in the diagnosis and treatment of acute graft rejection.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim , Doença Aguda , Algoritmos , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Tacrolimus (TAC) is the most important agent for maintenance immunosuppression and prevention of immunologic injury to the renal allograft, yet there remains no consensus on how best to monitor drug therapy. Both high TAC intrapatient variability and low TAC time in therapeutic range (TTR) have been associated with risk of de novo donor-specific antibodies (dnDSA). In this study, we hypothesized that the risk associated with high TAC coefficient of variation (CV) is a result of low TAC TTR rather than the variability itself. METHODS: We analyzed the risk of dnDSA, acute rejection, or death-censored graft loss by non-dosed-corrected TAC CV and TAC TTR during the first posttransplant year in a cohort of 538 patients with a median follow-up period of 4.1 years. RESULTS: Patients with CV >44.2% and TTR <40% (high intrapatient variability and low TTR) had a high risk of dnDSA (adjusted OR = 4.93, 95% confidence interval = 2.02-12.06, P < 0.001) and death-censored graft loss by 5 years (adjusted HR = 4.00, 95% confidence interval = 1.31-12.24, P = 0.015) when compared with patients with CV >44.2% and TTR ≥40% (high intrapatient variability and optimal TTR), while the latter patients had similar risk to patients with CV <44.2% (lower intrapatient variability). CONCLUSIONS: These data suggest that previously reported immunologic risk associated with high TAC intrapatient variability is due to time outside of therapeutic range rather than variability in and of itself when evaluating absolute non-dose-corrected TAC levels irrespective of reason or indication.
Assuntos
Inibidores de Calcineurina/uso terapêutico , Monitoramento de Medicamentos , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Imunossupressores/uso terapêutico , Isoanticorpos/sangue , Transplante de Rim , Tacrolimo/uso terapêutico , Adulto , Biomarcadores/sangue , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/sangue , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: De novo donor-specific antibody formation posttransplant is associated with decreased graft survival. It is not known whether mammalian target of rapamycin inhibitors may be advantageous or detrimental compared with mycophenolate in the prevention of de novo donor-specific antibody formation. MATERIALS AND METHODS: We compared 66 kidney and kidney-pancreas transplant recipients who received tacrolimus, mammalian target of rapamycin inhibitor, and prednisone (group 1; 36 of whom received everolimus and 30 of whom received sirolimus) versus 132 patients who received tacrolimus, mycophenolate, and prednisone (group 2) matched for age, sex, race, and type/timing of transplant from 2007 to 2012. RESULTS: Rates of de novo donor-specific antibody formation were comparable between groups at 1, 6, and 12 months (16.7%, 25.8%, and 28.8% for group 1 vs 9.8%, 15.2%, and 22.0% for group 2). There were no significant differences in class (I, II, or mixed), strength (mean fluorescence intensity) of de novo donor-specific antibody, glomerular filtration rate, proteinuria levels, or acute rejection between the groups. In those with de novo donor-specific antibody by 6 months, acute rejection was more common versus those without de novo donor-specific antibody formation (24.3% vs 5.6% at 6 mo; P = .002), with rates of 27.0% versus 6.8% at 1 year (P = .001) and 40.7% versus 11.3% at 2 years (P < .001). An associated reduction in glomerular filtration rate also occurred. CONCLUSIONS: Mammalian target of rapamycin inhibitors were neither protective nor permissive for de novo donor-specific antibody formation versus mycophenolate when used with clinically relevant tacrolimus dosing regimens.
Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Isoanticorpos/sangue , Transplante de Rim , Ácido Micofenólico/uso terapêutico , Transplante de Pâncreas , Serina-Treonina Quinases TOR/antagonistas & inibidores , Tacrolimo/uso terapêutico , Adulto , Biomarcadores/sangue , Colorado , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Histocompatibilidade , Hospitais Universitários , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
Antibody-mediated rejection has now been recognized as one of the most important causes of graft loss. Transplantation across HLA barriers and nonadherence can result in acute antibody-mediated rejection, which is associated with particularly worse graft outcomes. New technologies, including genomic studies and assays to detect and define donor-specific antibodies, have provided important insights into the pathophysiology and diagnosis of acute antibody-mediated rejection but have engendered many questions about the clinical application of these tests in the prognosis and prevention of this protean disease process. In this article, we review the pathophysiology of acute antibody-mediated rejection, the evolving diagnostic criteria, and specific challenges related to its prognosis, treatment, and prevention.
Assuntos
Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Antígenos HLA/imunologia , Terapia de Imunossupressão/métodos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Doença Aguda , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Transplante de Rim/métodos , Masculino , Cuidados Pré-Operatórios/métodos , Prevenção Primária/métodos , Prognóstico , Medição de Risco , Transplantados , Imunologia de Transplantes/fisiologiaRESUMO
Kidney allograft damage resulting from donor-specific anti-HLA antibody (DSA) activity has been identified as a key component of long-term graft attrition. DSA that persists following acute antibody-mediated rejection (AMR) episodes and/or DSA associated with chronic graft dysfunction have been shown to be particularly pathogenic. Despite the significantly negative effects of DSA on graft survival, there are currently no accepted treatment modalities. We have previously reported our experience using a regimen of high-dose (5 mg/kg) intravenous immunoglobulin (IVIG) treatment over 6 months for kidney recipients with detectable DSA either following an acute AMR episode or in association with chronic graft dysfunction. In this manuscript, we report further follow-up on this cohort of patients treated with a single regimen of high-dose IVIG. We show a continued significant lowering effect on DSA present following AMR, particularly class I DSA, while DSA associated with chronic graft dysfunction, particularly class II, remains resistant to the immunomodulatory effects of IVIG.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Antígenos HLA/imunologia , Histocompatibilidade , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Doença Aguda , Biomarcadores/sangue , Doença Crônica , Colorado , Monitoramento de Medicamentos , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Masculino , Monitorização Imunológica , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Postkidney transplant donor-specific antibodies (DSA) have been identified as important contributors to graft loss. Few therapeutic options exist and have been met with limited success. We report outcomes in patients with de novo DSA and graft damage treated with a protocol of high-dose intravenous immunoglobulin (IVIG). METHODS: Retrospective analysis of 28 kidney transplant recipients with de novo DSA and graft damage in the form of either chronic graft dysfunction (group 1, n=20) or a recent previous acute antibody-mediated rejection (AMR) episode (group 2, n=8) prescribed a standard regimen of high-dose (5 g/kg) IVIG dosed over 6 months. RESULTS: Mean fluorescence intensity (MFI) of 70 total DSA decreased by 12%at the end of treatment (T1, P=0.14) and by 18%at last follow up (T2, P=0.035) compared with treatment initiation (T0) MFI. The most robust effect was seen in class I DSA (37% decrease at T2 versus T0, P=0.05) and in DSA from patients in group 2 (52% decrease at T2 versus T0, P=0.008). Graft function stabilized in patients in group 2 but continued to decline in those in group 1. CONCLUSION: High-dose IVIG resulted in modest DSA MFI reductions in patients with previous graft damage, with a larger effect occurring in class I DSA in patients with a previous acute AMR. There was no clinical treatment benefit in patients with ongoing chronic graft damage, whereas high-dose IVIG may reduce the risk of chronic graft dysfunction in those with an acute AMR event.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Histocompatibilidade , Imunoglobulinas Intravenosas/administração & dosagem , Imunossupressores/administração & dosagem , Isoanticorpos/imunologia , Transplante de Rim/efeitos adversos , Doença Aguda , Doença Crônica , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/imunologia , Humanos , Isoanticorpos/sangue , Masculino , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
We summarize in this manuscript our donor specific antibody (DSA) screening experience in the past six years as it applies to pre-existing DSA, de novo DSA, and post-transplant DSA treatment. Of 547 patients receiving a kidney or kidney/pancreas with negative pre-transplant flow cytometry crossmatch (FCXM), 196 had DSA (mean fluorescence intensity, MFI >or= 500) detected prior to transplant by single antigen bead analysis. Acute rejection rates at one year were similar in DSA+ versus DSA- (15% versus 12%, respectively, p=0.22), although acute rejection occurred earlier in the DSA+ group. De novo DSA was detected in 65 of 261 patients (27%). All DSA was detected within the first posttransplant year. While acute rejection was more likely in patients with de novo DSA (29% versus 9.5% in those with no DSA), prospective DSA screening failed to predict this outcome as DSA was detected at the time of or after a rejection episode in 16 of 19 patients with both DSA and acute rejection. Two-year estimated graft survival was significantly worse in patients with versus without DSA, but was identical when removing patients with a prior acute rejection episode from the analysis. We have used a protocol of high dose (5 gm/kg) intravenous immunoglobulin infused over the course of 6 months in patients with DSA and either chronic graft dysfunction or following a recent acute antibody mediated rejection (AMR) episode. DSA MFI was reduced by 18% from the time of initiation to last follow up. This effect was largely due to reductions in class I DSA (-37%) and DSA in patients with a recent acute AMR (-51.5%), with a minimal effect on class II DSA and DSA in patients with chronic graft dysfunction. Despite treatment directed at antibody-producing plasma cells, antibody levels either persisted or worsened with no improvement in graft function. Overall, DSA is more amendable to treatment when associated with a recent acute rejection event.
Assuntos
Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/imunologia , Transplante de Rim/estatística & dados numéricos , Doença Aguda , Colorado , Hospitais Universitários , Humanos , Isoanticorpos/sangue , Período Pós-Operatório , Período Pré-Operatório , Estudos Prospectivos , Estudos Soroepidemiológicos , Doadores de TecidosRESUMO
Bisphenol A (BPA) is a ubiquitous high volume industrial chemical that is an estrogen and an environmental endocrine disrupting chemical. Bisphenol A is used extensively in the production of consumer goods, polycarbonate plastics, epoxy resins and coatings used to line metallic food and beverage cans. There is great concern regarding the possible harmful effects from exposures that result from BPA leaching into foods and beverages from packaging or storage containers. The objective of this study was to independently assess whether BPA contamination of water was occurring from different types of reusable drinking bottles marketed as alternatives to BPA-containing polycarbonate plastics. Using a sensitive and quantitative BPA-specific competitive enzyme-linked immunosorbent assay we evaluated whether BPA migrated into water stored in polycarbonate or copolyester plastic bottles, and different lined or unlined metallic reusable water bottles. At room temperature the concentration of BPA migrating from polycarbonate bottles ranged from 0.2 to 0.3 mg L⻹. Under identical conditions BPA migration from aluminium bottles lined with epoxy-based resins was variable depending on manufacturer ranging from 0.08 to 1.9 mg L⻹. Boiling water significantly increased migration of BPA from the epoxy lined bottles. No detectable BPA contamination was observed in water stored in bottles made from Tritan™ copolyester plastic, uncoated stainless steel, or aluminium lined with EcoCare™. The results from this study demonstrate that when used according to manufacturers' recommendations reusable water bottles constructed from "BPA-free" alternative materials are suitable for consumption of beverages free of BPA contamination.
Assuntos
Alumínio/química , Embalagem de Alimentos/métodos , Fenóis/análise , Plásticos/química , Reciclagem , Aço Inoxidável/química , Água/química , Compostos Benzidrílicos , Disruptores Endócrinos/análise , Disruptores Endócrinos/química , Fenóis/químicaRESUMO
We have previously shown poor outcomes in a cohort of kidney recipients with de novo donor specific anti-HLA antibodies (DSA) detected via post-transplant screening, were due to prior acute rejection (AR) episodes. In this report, we sought to identify DSA characteristics associated with poor outcomes in the absence of AR. All living and cadaveric donor kidney/ kidney-pancreas recipients from 9/07 to 10/09 were screened for class I and II DSA at 1, 6, 12, and 24 months post-transplant, in addition to whenever clinically indicated, using single antigen beads and Luminex technology. Mean florescence intensity (MFI) > 500 was defined as positive. Compared to DSA(-) patients, those who developed both class I and II DSA experienced worse graft survival (p < .001). Graft survival in those with class I or II alone was unchanged. Patients with DSA MFI > 6000 experienced worse 1-year modification of diet in renal disease glomerular filtration rate (MDRD GFR) (p = 0.022) and 2-year graft survival (p = .026) compared to DSA(-) patients, whereas graft survival in groups with lower antibody strength was not statistically different. The effect of DSA class and strength was lost when removing patients with AR from the analysis. In sum, with a mean follow-up of 29 months, the presence of combined de novo class I and II DSA as well as DSA with MFI > 6000, is associated with worse graft outcomes only in association with AR episodes.