RESUMEN
BACKGROUND: Antibody-mediated rejection (ABMR) is the leading cause of kidney graft loss worldwide. Criteria for acute humoral rejection (currently labeled active humoral rejection) established by the 2007 Banff classification are highly specific but lack sensitivity. Modifications to the Banff classification were introduced for its 2013 and 2017 versions in order to identify more cases of this entity. PURPOSE: We intend to demonstrate that, compared to its 2007 version, the 2017 Banff classification bears an improved capacity for graft loss prediction when histologic criteria for active ABMR are met. PATIENTS AND METHODS: Single-center retrospective cohort study. A random sample of 201 kidney recipients who underwent a graft biopsy since January 2004 was analyzed. Patients were classified as ever developing histologic characteristics of acute ABMR (2007 Banff) or not and renal survival between groups was compared. The same patients were then classified as ever developing histologic characteristics of active ABMR (2017 Banff) or not and renal survival was again compared. Presence of circulating donor-specific antibodies (DSA) was not taken into consideration. RESULTS: Patients were followed for a median 13.9⯱â¯7.9â¯years, during which grafts were biopsied on 537 occasions (2.7⯱â¯1.6 biopsies per graft). Baseline eGFR was 73.26⯱â¯17.6â¯ml/min and baseline creatinine 1.14⯱â¯0.25â¯mg/dl. Graft loss occurred in 38 recipients (18.9%) mainly due to ABMR (60.5%). Acute ABMR (2007 Banff) was identified in 11 recipients (5.5%) and graft survival did not differ between groups with and without active ABMR occurrence (log-rank pâ¯=â¯0.939). Active ABMR (2017 Banff) was found in 59 recipients (29%) and graft survival was better from the second post-transplant year onward in the group of patients without active ABMR occurrence (log-rank pâ¯=â¯0.001). Moderate microvascular inflammation was present in 89.6% of the 48 additional patients with active ABMR. CONCLUSION: The 2017 Banff classification identifies more patients who develop active ABMR and stratifies graft loss risk better than the 2007 version.
Asunto(s)
Glomerulonefritis Membranosa/inmunología , Rechazo de Injerto/inmunología , Inflamación/inmunología , Isoanticuerpos/sangre , Trasplante de Riñón , Microvasos/inmunología , Adulto , Biopsia , Enfermedad Crónica , Estudios de Cohortes , Complemento C4/metabolismo , Femenino , Estudios de Seguimiento , Glomerulonefritis Membranosa/clasificación , Rechazo de Injerto/clasificación , Humanos , Inflamación/clasificación , Masculino , Microvasos/patología , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Riesgo , Adulto JovenRESUMEN
La biopsia hepática de los aloinjertos sigue siendo considerada el estándar de oro y juega un papel importante e integral en la interpretación y explicación de los cambios que puedan ocurrir en respuesta a alteraciones en las pruebas de la función o bioquímica hepática, anomalías funcionales o alteración en las imágenes diagnósticas, las cuales pueden, o no, ir acompañadas de síntomas. También es útil en el seguimiento o biopsias por protocolo (1-3). La evaluación de biopsias, después del trasplante, puede ser difícil debido a que es muy amplio el espectro de las complicaciones que pueden presentarse en el período postrasplante; más aún, cuando muchas de ellas necesitan un diagnóstico y tratamiento inmediato. La patología más frecuente es el rechazo agudo. Sin embargo, también pueden observarse cambios de perfusión/reperfusión, alteraciones funcionales, recidiva de enfermedad de base, lesión de la vía biliar, lesiones vasculares, infecciones oportunistas, patologías de novo, como la hepatitis autoinmune, hepatitis crónica idiopática postrasplante, toxicidad farmacológica o tumores, entre otras patologías (4). En este artículo relacionado con la patología del trasplante hepático se tratarán las patologías más frecuentes, no quirúrgicas, en el período postrasplante temprano, con un enfoque histopatológico dirigido a las dificultades y controversias para una adecuada correlación clínico-patológica.
Biopsies of liver allografts are still considered to be the gold standard. They play an important and integral role in the interpretation and explanation of changes that may occur in response to alterations in function tests, in the interpretation and explanation of liver biochemistry, in the interpretation and explanation of functional abnormalities, and in the interpretation and explanation of diagnostic images (whether or not accompanied by symptoms). Biopsies are also useful for monitoring and are often part of the protocol (1-3). The evaluation of biopsy samples after transplantation can be difficult especially because of the very broad spectrum of complications that may arise in the post-transplant period. Many of them require immediate diagnosis and treatment despite this difficulty. Although the most common condition is acute rejection, many other conditions and disorders can be observed. They include perfusion/reperfusion alterations, functional impairment, recurrence of underlying diseases, injury to the bile duct, vascular lesions, opportunistic infections, de novo pathologies such as autoimmune hepatitis, post-transplant idiopathic chronic hepatitis, drug toxicity, and tumors (4). This is the second article about the pathology of liver transplantation. It discusses the most common pathologies in the early post-transplant period and provides a histopathological approach towards difficulties and controversies for adequate clinicopathological correlation.
Asunto(s)
Humanos , Masculino , Femenino , Biopsia , Endotelio , Rechazo de Injerto , Trasplante de Hígado , Disfunción Primaria del Injerto , Daño por ReperfusiónRESUMEN
INTRODUCTION: C4d is a marker of antibody-mediated rejection (ABMR) in kidney allografts, although cellular rejection also have C4d deposits. OBJECTIVE: To correlate C4d expression with clinico-pathological parameters and graft outcomes at three years. METHODS: One hundred forty six renal transplantation recipients with graft biopsies by indication were included. C4d staining was performed by paraffin-immunohistochemistry. Graft function and survival were measured, and predictive variables of the outcome were determined by multivariate Cox regression. RESULTS: C4d staining was detected in 48 (31 percent) biopsies, of which 23 (14.7 percent) had diffuse and 25 (16 percent) focal distribution. Pre-transplantation panel reactive antibodies ( percentPRA) class I and II were significantly higher in C4d positive patients as compared to those C4d negative. Both glomerulitis and pericapillaritis were associated to C4d (p = 0.002 and p < 0.001, respectively). The presence of C4d in biopsies diagnosed as no rejection (NR), acute cellular rejection (ACR) or interstitial fibrosis/ tubular atrophy (IF/TA) did not impact graft function or survival. Compared to NR, ACR and IF/TA C4d-, patients with ABMR C4d+ had the worst graft survival over 3 years (p = 0.034), but there was no difference between ABMR versus NR, ACR and IF/TA that were C4d positive (p = 0.10). In Cox regression, graft function at biopsy and high percentPRA levels were predictors of graft loss. CONCLUSIONS: This study confirmed that C4d staining in kidney graft biopsies is a clinically useful marker of ABMR, with well defined clinical and pathological correlations. The impact of C4d deposition in other histologic diagnoses deserves further investigation.
INTRODUÇÃO: A fração do complemento C4d é um marcador de rejeição mediada por anticorpos (RMA) em aloenxertos renais, embora na rejeição celular também se observem depósitos de C4d. OBJETIVOS: Correlacionar a expressão de C4d com parâmetros clínicopatológicos e a evolução do enxerto renal em três anos. MÉTODOS: Foram incluídos 146 receptores de transplante renal com biópsias por indicação. A marcação de C4d foi feita por imuno-histoquímica em parafina. Foram medidas a função e a sobrevida do enxerto e determinadas as variáveis preditivas de sua evolução por meio de modelo de regressão de Cox. RESULTADOS: A marcação positiva para C4d foi detectada em 48 (31 por cento) biópsias, das quais 23 (14,7 por cento) tinham marcação difusa e 25 (16 por cento), focal. A reatividade contra painel ( por centoPRA) de classe I e II pré-transplante foi significativamente maior nos pacientes C4d+ quando comparada aos C4d-. Tanto glomerulite quanto pericapilarite foram associadas com C4d (p = 0,002 e p < 0,001, respectivamente). A presença de C4d em biópsias sem rejeição (SR), rejeição celular aguda (RCA) ou fibrose intersticial/atrofia tubular (FI/AT) não teve impacto na função ou na sobrevida do enxerto. Comparados a indivíduos com SR, RCA e FI/AT C4d-, pacientes com RMA C4d+ tiveram pior sobrevida do enxerto em 3 anos (p = 0,034), mas não houve diferença entre RMA versus SR, RCA e FI/AT C4d+ (p = 0,10). Na regressão de Cox, função do enxerto no momento da biópsia e por centoPRA alto foram preditores de perda do enxerto. CONCLUSÕES: A pesquisa de C4d em biópsias do enxerto renal é útil para identificar RMA, com correlações clínicopatológicas bem definidas. O impacto do C4d em outros diagnósticos histológicos necessita de investigação adicional.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , /análisis , /biosíntesis , Trasplante de Riñón/patología , Fragmentos de Péptidos/análisis , Fragmentos de Péptidos/biosíntesis , Supervivencia de Injerto , Inmunohistoquímica , Trasplante de Riñón/fisiología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
El trasplante renal es el tratamiento de elección para los pacientes con falla renal terminal. Las principales causas de pérdida de injertos son la muerte del paciente con injerto funcionante, especialmente de causa cardiovascular y la nefropatía crónica del injerto, con una pérdida crónica de injertos que resulta en un problema relevante. Dentro de las causas de nefropatía crónica destaca la causa inmunológica. Una de las causas de pérdida de injertos de origen inmunológico son los rechazos agudos, los que pueden ser de origen celular y humoral. Por otra parte, y a pesar de los avances en la comprensión de los mecanismos responsables de la inmunidad celular y el desarrollo de nuevas drogas inmunosupresoras (DIS), el rechazo mediado por anticuerpos o humoral aparece hoy como un peligro para la sobrevida del injertos a corto y a largo plazo. Afortunadamente el tratamiento del rechazo agudo humoral con drogas específicas ha resultado exitoso, sin embargo no ha ocurrido lo mismo con el rechazo mediado por anticuerpos de presentación más tardía, posiblemente por su comportamiento subclínico y un diagnóstico tardío, permaneciendo como un nuevo desafío recientemente reconocido. Por otra parte y basado en el exitoso tratamiento del RAH, se ha planteado mejorar las expectativas de llegar a realizar un trasplante a los pacientes sensibilizados. Esto es posible conseguir aplicando protocolos de desensibilización que se basan en la utilización de las mismas drogas para tratar RAH, consiguiendo ampliar las posibilidades de trasplante. El éxito de éstas es relativo al tipo de protocolos y a la intensidad de la sensibilización. La sobrevida del injerto en esta situación es plausible en la gran mayoría de los casos, sin embargo existe riesgo de presentar rechazo agudo humoral, y más complejo aún es el hecho que la sobrevida a largo plazo de los injertos sigue siendo todavía desconocida.
Renal Transplantation is the therapy of choice for patients with end-stage renal failure. The main causes for graft losses are patient death with functioning graft, mainly of cardiovascular etiology and chronic allograft nephropathy. Among the causes of chronic allograft nephropathy, the immunological ones are among the most important; one of them are the acute rejection episodes, which can be of cellular or humoral etiology; in addition, and despite the understanding of the mechanisms responsible for the cell immunity and the development of new immunosuppressive drugs (DIS) the antibody mediated rejection o humoral rejection has become today a danger for the short and long term allograft survival. Fortunately, the treatment of acute humoral rejection with specific drugs has become successful, however, the situation is different with late occurring antibody mediated rejection episodes, probably due to its subclinical behavior and a late diagnosis, remaining as a new challenge recently recognized. On the other hand based on the successful treatment of the RAH, expectations of performing a transplant in sensitized patients have been improved. This is possible to achieve using desensitizing protocols base don the same drugs used to treat RAH, thus increasing transplant possibilities. The success is related to the type of protocols and the intensity of the desensitizing. Graft survival in this situation is possible in the large majority of cases, however, the risk of acute humoral rejection is present, but even more complex is the fact thatlong-term survival is still unknown.