RESUMEN
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.
Asunto(s)
Rechazo de Injerto , Tacrolimus , Rechazo de Injerto/etiología , Supervivencia de Injerto , Antígenos HLA/genética , Antígenos HLA-DR , Prueba de Histocompatibilidad , Humanos , Estados UnidosRESUMEN
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.
Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Monitoreo de Drogas , Rechazo de Injerto/prevención & control , Antígenos HLA/inmunología , Inmunosupresores/uso terapéutico , Isoanticuerpos/sangre , Trasplante de Riñón , Tacrolimus/uso terapéutico , Adulto , Biomarcadores/sangre , Inhibidores de la Calcineurina/efectos adversos , Inhibidores de la Calcineurina/sangre , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Rechazo de Injerto/mortalidad , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/sangre , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tacrolimus/efectos adversos , Tacrolimus/sangre , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/uso terapéutico , Trasplante de Riñón , Enfermedad Aguda , Algoritmos , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Medición de Riesgo , Factores de Riesgo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Rechazo de Injerto/diagnóstico , Supervivencia de Injerto/inmunología , Isoanticuerpos/sangre , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Tacrolimus/efectos adversos , Donantes de Tejidos , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Rechazo de Injerto/sangre , Rechazo de Injerto/etiología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Antígenos HLA/inmunología , Humanos , Inmunosupresores/efectos adversos , Isoanticuerpos/inmunología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
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.
Asunto(s)
Rechazo de Injerto/prevención & control , Supervivencia de Injerto/efectos de los fármacos , Inmunosupresores/uso terapéutico , Isoanticuerpos/sangre , Trasplante de Riñón , Ácido Micofenólico/uso terapéutico , Trasplante de Páncreas , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Tacrolimus/uso terapéutico , Adulto , Biomarcadores/sangre , Colorado , Quimioterapia Combinada , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Histocompatibilidad , Hospitales Universitarios , Humanos , Inmunosupresores/efectos adversos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Ácido Micofenólico/efectos adversos , Trasplante de Páncreas/efectos adversos , Prednisona/uso terapéutico , Estudios Retrospectivos , Tacrolimus/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Antígenos HLA/inmunología , Terapia de Inmunosupresión/métodos , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Enfermedad Aguda , Femenino , Humanos , Fallo Renal Crónico/diagnóstico , Trasplante de Riñón/métodos , Masculino , Cuidados Preoperatorios/métodos , Prevención Primaria/métodos , Pronóstico , Medición de Riesgo , Receptores de Trasplantes , Inmunología del Trasplante/fisiologíaRESUMEN
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.
Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Hipertensión/etiología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Adulto , Factores de Edad , Determinación de la Presión Sanguínea , Niño , Femenino , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Hipertensión/epidemiología , Incidencia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/métodos , Masculino , Pronóstico , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Histocompatibilidad , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunosupresores/administración & dosificación , Isoanticuerpos/inmunología , Trasplante de Riñón/efectos adversos , Enfermedad Aguda , Enfermedad Crónica , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/inmunología , Humanos , Isoanticuerpos/sangre , Masculino , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Negro o Afroamericano/etnología , Rechazo de Injerto/etnología , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/etnología , Adulto , Etnicidad , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
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.
Asunto(s)
Rechazo de Injerto/tratamiento farmacológico , Antígenos HLA/inmunología , Histocompatibilidad , Inmunoglobulinas Intravenosas/administración & dosificación , Inmunosupresores/administración & dosificación , Isoanticuerpos/sangre , Trasplante de Riñón/efectos adversos , Enfermedad Aguda , Biomarcadores/sangre , Enfermedad Crónica , Colorado , Monitoreo de Drogas , Femenino , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/inmunología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Masculino , Monitorización Inmunológica , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Micropartículas Derivadas de Células/efectos de los fármacos , Ciclosporina/toxicidad , Células Endoteliales/efectos de los fármacos , Inmunosupresores/toxicidad , Animales , Micropartículas Derivadas de Células/metabolismo , Activación de Complemento/efectos de los fármacos , Complemento C3/análisis , Células Endoteliales/ultraestructura , Riñón/efectos de los fármacos , Riñón/patología , Trasplante de Riñón , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/patología , Ratones , Ratones Endogámicos C57BL , Tacrolimus/uso terapéuticoRESUMEN
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.
Asunto(s)
Lesión Renal Aguda/etiología , Trasplante de Riñón/efectos adversos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/prevención & control , Biomarcadores/análisis , Funcionamiento Retardado del Injerto/diagnóstico , Funcionamiento Retardado del Injerto/etiología , Selección de Donante , Perfilación de la Expresión Génica , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Humanos , Recolección de Tejidos y ÓrganosRESUMEN
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.
Asunto(s)
Rendimiento Atlético , Fricción , Carrera/fisiología , Adolescente , Adulto , Humanos , Masculino , Poaceae , Equipo Deportivo , Propiedades de Superficie , Factores de Tiempo , Adulto JovenRESUMEN
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.
Asunto(s)
Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Antígenos HLA/inmunología , Isoanticuerpos/inmunología , Trasplante de Riñón/estadística & datos numéricos , Enfermedad Aguda , Colorado , Hospitales Universitarios , Humanos , Isoanticuerpos/sangre , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Prospectivos , Estudios Seroepidemiológicos , Donantes de TejidosRESUMEN
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.
Asunto(s)
Aluminio/química , Embalaje de Alimentos/métodos , Fenoles/análisis , Plásticos/química , Reciclaje , Acero Inoxidable/química , Agua/química , Compuestos de Bencidrilo , Disruptores Endocrinos/análisis , Disruptores Endocrinos/química , Fenoles/químicaRESUMEN
BACKGROUND: Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes. METHODS: From September 2007 through September 2009, 244 consecutively transplanted kidney and kidney/pancreas recipients without pretransplant DSA were screened for de novo DSA at 1, 6, 12, and 24 months and when clinically indicated. RESULTS: DSA was detected in 27% of all patients by protocol or indication screening. Patients with DSA (DSA+) were significantly more likely to have experienced acute rejection (AR) compared with no DSA (DSA-) (29% vs. 9.5%, P<0.001), and lower estimated 2-year graft survival (83% vs. 98%, P<0.001). Only 3 of 19 DSA (+) patients with AR had DSA detected before the AR episode. When excluding patients with AR, 2-year graft survival was similar between DSA (+) and DSA (-) patients (100% vs. 99%) as was estimated glomerular filtration rate. Patients with DSA detected by protocol screening had similar outcomes compared with DSA (-), whereas those with DSA detected by indication experienced significantly worse outcomes. CONCLUSIONS: Patients with de novo DSA experience worse graft outcomes due to previous/concurrent episodes of AR. A prospective DSA screening protocol failed to identify patients at risk for AR or poor short-term graft outcomes.