Polyclonal anti T-lymphocyte antibody therapy monitoring in kidney transplant recipients: comparison of CD3+ T cell and total lymphocyte counts / Monitoramento da terapia com anticorpo policlonal antilinfócitos T em transplantados renais: comparação da contagem de células T CD3+ e de linfócitos totais

ABSTRACT Objective: To investigate the correlation between total lymphocyte and CD3+ T cell counts in peripheral blood in renal transplant patients treated with anti-thymocyte globulin, and discuss related outcomes. Methods: A single-center, retrospective study involving 226 patients submitted to kidney transplant between 2008 and 2013, and treated with anti-thymocyte globulin for induction or treatment of cellular rejection. Doses were adjusted according to CD3+ T cell or total lymphocyte counts in peripheral blood. Results: A total of 664 paired samples were analyzed. The Spearman's correlation coefficient was 0.416 (p<0.001) for all samples combined; the overall Kappa coefficient was 0.267 (p<0.001). Diagnostic parameters estimated based on total lymphocyte counts were also calculated using the number of CD3+ T cells (gold standard), with a cut off of >20 cells/mm3. Conclusion: Total lymphocyte and CD3+ T cell counts in peripheral blood are not equivalent monitoring strategies in anti-thymocyte globulin therapy.

RESUMO Objetivo: Investigar a correlação entre a contagem de linfócitos totais e células T CD3+ no sangue periférico em receptores de transplante renal submetidos a tratamento com globulina antitimocitária, e discutir resultados relacionados. Métodos: Estudo retrospectivo de centro único envolvendo 226 pacientes submetidos a transplante renal entre 2008 e 2013 e tratados com globulina antitimocitária, para fins de indução ou tratamento de rejeição celular. As doses foram ajustadas de acordo com a contagem de células T CD3+ ou linfócitos totais no sangue periférico. Resultados: No total, 664 amostras pareadas foram analisadas. O coeficiente de correlação de Spearman para as amostras em geral foi de 0,416 (p<0,001) e o coeficiente Kappa, de 0,267 (p<0,001). Os parâmetros diagnósticos estimados com base na contagem de linfócitos totais foram recalculados, empregando-se o número de células T CD3+ (padrão-ouro) e adotando-se o ponto de corte >20 células/mm3. Conclusão: A contagem de linfócitos totais no sangue periférico não substitui a contagem de células T CD3+ enquanto estratégia de monitorização da terapia à base de globulina antitimocitária.

Sobrevida de pacientes e injerto en niños con trasplante renal: experiencia del Hospital Garrahan en dos períodos / Patient and graft survival in children with a kidney transplant: The experience at Garrahan Hospital over two periods

En adultos y niños con trasplante renal (TxR) la sobrevida de paciente e injerto ha mejorado. En Argentina no existen datos de sobrevida en niños con TxR en diferentes décadas. El objeto de este trabajo fue valorar en niños con TxR sobrevida de paciente e injerto y analizar causas de muerte, perdida de injerto y factores de riesgo de pérdida. Dado que desde el año 2001 se unificaron prácticas de diagnóstico y tratamiento, se compararon dos periodos: 1988-2000 y 2001-2015. Se incluyeron 773 niños. A 1, 3, 5, 7 y 10 años, En TxR de DV (n=327), la sobrevida del paciente fue de 99%, 99%, 98%, 95%, 95% vs 100% y 96%, 96%, 96% y 96% (p=0.74); la del injerto de 97%, 91%, 85%, 78% y 67% vs 95%, 88%, 85%, 81% y 76% (p=0.81). En TxR de DC (n=446) la sobrevida de paciente fue de 97%, 93%, 90%, 89% y 87% en el 1er. periodo vs. 100%, 99% y 98% 98% y 98% en el 2do (p<0.001); la del injerto de 83%, 75%, 68%, 64% y 52% vs. 95%, 87%, 83%, 76% y 61% respectivamente (p<0. 001). El Rechazo Crónico fue la 1er causa de perdida (61% vs 62%); la 2da la muerte del paciente con injerto funcionante. La sepsis bacteriana fue la 1era causa de muerte (56% vs 67%). Ningún niño falleció por neoplasia entre el 2001 y 2015. En DV, fueron predictores de perdida de injerto: DGF (HR: 4.8; p<0.001), edad al TxR > 12 años (HR: 2.7; p=0.002) y RA tardío (HR: 2.1; p=0.009). En DC la necesidad de diálisis en la 1er semana post TxR (DGF): (HR: 4.4; p<0.001), el rechazo agudo (RA) tardío (HR: 3.7; p<0.001), GSFS como causa de IRC (HR: 2.5; p=0.01), y RA temprano (HR: 2.2; p=0.02). Conclusión: En el 2do periodo la sobrevida de paciente e injerto los TxR con DC mejoro, y en los TxR con DV no tuvo cambios. El rechazo crónico continúa siendo la 1era causa de perdida. Ningún paciente tuvo neoplasia (AU)

Patient and graft survival in kidney transplantation (KTx) has improved. In Argentina there are no data comparing transplant outcomes in children over different eras. The aim of this study was to evaluate patient and graft survival in children with KTx and to analyze cause of death, graft loss, and risk factors of graft loss. As diagnostic and treatment practices were unified in 2001, two periods were compared: 1988-2000 and 2001-2015. Overall, 773 children were included. Survival at 1, 3, 5, 7, and 10 years after a living-related donor (LRD) KTx was 99%, 99%, 98%, 95%, 95% vs 100% y 96%, 96%, 96% and 96% (p=0.74); graft survival was 97%, 91%, 85%, 78% y 67% vs 95%, 88%, 85%, 81%, and 76% (p=0.81). Patient survival after deceased donor (DD) KTx (n=446) was 97%, 93%, 90%, 89%, and 87% in the 1st period vs. 100%, 99% y 98% 98%, and 98% in the 2nd (p<0.001); graft survival was 83%, 75%, 68%, 64%, and 52% vs. 95%, 87%, 83%, 76%, and 61%, respectively (p<0. 001). Chronic rejection was the first cause of graft loss (61% vs 62%); the second was death of the patient with a functioning graft. Bacterial sepsis was the first cause of death (56% vs 67%). None of the patients died because of malignancies between 2001 and 2015. Among LRD transplants predicting factors of graft loss were: DGF (HR: 4.8; p<0.001), age at KTx >12 years (HR: 2.7; p=0.002), and late acute rejection (AR) (HR: 2.1; p=0.009). Among DD need for dialysis in the first week post-KTx (DGF): (HR: 4.4; p<0.001), late AR (HR: 3.7; p<0.001), FSGS-related CFR (HR: 2.5; p=0.01), and early AR (HR: 2.2; p=0.02). Conclusion: In the second period patient and graft survival after DD improved, while that of KTx with LRD remained unchanged. Chronic rejection continues being the first cause of graft loss. None of the patients developed malignancies.

LATE ACUTE REJECTION IN LIVER TRANSPLANT: A SYSTEMATIC REVIEW / REJEIÇÃO AGUDA TARDIA NO TRANSPLANTE DE FÍGADO: REVISÃO SISTEMÁTICA

Introduction:Late acute rejection leads to worse patient and graft survival after liver transplantation.Aim:To analyze the reported results published in recent years by leading transplant centers in evaluating late acute rejection and update the clinical manifestations, diagnosis and treatment of liver transplantation. Method:Systematic literature review through Medline-PubMed database with headings related to late acute rejection in articles published until November 2013 was done. Were analyzed demographics, immunosuppression, rejection, infection and graft and patient survival rates. Results:Late acute rejection in liver transplantation showed poor results mainly regarding patient and graft survival. Almost all of these cohort studies were retrospective and descriptive. The incidence of late acute rejection varied from 7-40% in these studies. Late acute rejection was one cause for graft loss and resulted in different outcomes with worse patient and graft survival after liver transplant. Late acute rejection has been variably defined and may be a cause of chronic rejection with worse prognosis. Late acute rejection occurs during a period in which the goal is to maintain lower immunosuppression after liver transplantation. Conclusion:The current articles show the importance of late acute rejection. The real benefit is based on early diagnosis and adequate treatment at the onset until late follow up after liver transplantation.

RESUMO Introdução:A rejeição aguda tardia apresenta resultados com pior sobrevida do paciente e do enxerto após o transplante de fígado.Objetivo:Analisar os resultados publicados na literatura nos últimos anos pelos principais centros de transplante sobre o tema rejeição aguda tardia para atualização analisando suas manifestações clínicas, diagnóstico e tratamento. Método:Foi realizado uma revisão sistemática da literatura, utilizando o banco de dados PubMed/Medline com os descritores relacionados à rejeição aguda tardia nos artigos publicados até novembro de 2013. Foram analisados dados demográficos, imunossupressão, rejeição, infecção, bem como as taxas de sobrevida do enxerto e do paciente. Resultados:A rejeição aguda tardia no pós transplante de fígado mostra pior resultado na sobrevida do enxerto e do paciente. A grande maioria dos estudos foram coortes retrospectivas e descritivas. A incidência de rejeição aguda tardia variou de 7-40% a partir destes estudos. A rejeição aguda tardia é uma das causas de perda do enxerto. Rejeição aguda tardia tem sua definição variável definida em relação ao tempo. Sua evolução apresenta resultado diferente em relação à sobrevida do enxerto, podendo evoluir para rejeição crônica, apresentando pior prognóstico. A rejeição aguda tardia está presente no momento em que se tende a manter menor imunossupressão, alguns meses depois transplante. Conclusão:Os artigos atuais mostram a importância da rejeição aguda tardia. O benefício real está no diagnóstico precoce e no tratamento adequado durante o episódio e no seguimento tardio após transplante de fígado.

Issues in solid-organ transplantation in children: translational research from bench to bedside

In this review, we identify important challenges facing physicians responsible for renal and cardiac transplantation in children based on a review of the contemporary medical literature. Regarding pediatric renal transplantation, we discuss the challenge of antibody-mediated rejection, focusing on both acute and chronic antibody-mediated rejection. We review new diagnostic approaches to antibody-mediated rejection, such as panel-reactive antibodies, donor-specific cross-matching, antibody assays, risk assessment and diagnosis of antibody-mediated rejection, the pathology of antibody-mediated rejection, the issue of ABO incompatibility in renal transplantation, new therapies for antibody-mediated rejection, inhibiting of residual antibodies, the suppression or depletion of B-cells, genetic approaches to treating acute antibody-mediated rejection, and identifying future translational research directions in kidney transplantation in children. Regarding pediatric cardiac transplantation, we discuss the mechanisms of cardiac transplant rejection, including the role of endomyocardial biopsy in detecting graft rejection and the role of biomarkers in detecting cardiac graft rejection, including biomarkers of inflammation, cardiomyocyte injury, or stress. We review cardiac allograft vasculopathy. We also address the role of genetic analyses, including genome-wide association studies, gene expression profiling using entities such as AlloMap®, and adenosine triphosphate release as a measure of immune function using the Cylex® ImmuKnow™ cell function assay. Finally, we identify future translational research directions in heart transplantation in children.

Clinical recommendations for postoperative care after heart transplantation in children: 21 years of a single-center experience

Heart transplantation is an option for children with complex congenital heart disease and cardiomyopathies. A patient's quality of life and long-term survival depend on successful management of the surgical complications and adverse side effects of immunosuppression. The purpose of this review was to summarize the practical management of postoperative care in this patient population and to make recommendations for the future.

Safety and Efficacy of Transarterial Nephrectomy as an Alternative to Surgical Nephrectomy

OBJECTIVE: To evaluate the safety and efficacy of transarterial nephrectomy, i.e., complete renal artery embolization, as an alternative to surgical nephrectomy. MATERIALS AND METHODS: This retrospective study included 11 patients who underwent transarterial nephrectomy due to a high risk of surgical nephrectomy or their refusal to undergo surgery during the period from April 2002 to February 2013. Medical records and radiographic images were reviewed retrospectively to collect information regarding underlying etiologies, clinical presentations and embolization outcomes. RESULTS: The underlying etiologies for transarterial nephrectomy included recurrent hematuria (chronic transplant rejection [n = 3], arteriovenous malformation or fistula [n = 3], angiomyolipoma [n = 1], or end-stage renal disease [n = 1]), inoperable renal or ureteral injury (n = 2), and ectopic kidney with urinary incontinence (n = 1). The technical success rate was 100%, while clinical success was achieved in eight patients (72.7%). Subsequent surgical nephrectomy was required for three patients due to an incomplete nephrectomy effect (n = 2) or necrotic pyelonephritis (n = 1). Procedure-related complications were post-infarction syndrome in one patient and necrotic pyelonephritis in another patient. Of four patients with follow-up CT, four showed renal atrophy and two showed partial renal enhancement. No patient developed a procedure-related hypertension. CONCLUSION: Transarterial nephrectomy may be a safe and effective alternative to surgical nephrectomy in patients with high operative risks.

Strategies for local gene therapy of corneal allograft rejection

Penetrating keratoplasty is the most common type of tissue transplant in humans. Irreversible immune rejection leads to loss of vision and graft failure. This complex immune response further predisposes future corneal transplants to rejection and failure. A diverse armamentarium of surgical and pharmacologic tools is available to improve graft survival. In this review, we will discuss the various gene therapeutic strategies aimed at potentiating the anterior chamber-associated immune deviation to extend graft survival

Role of Plasma Exchange in ABO-incompatible Kidney Transplantation

BACKGROUND: In the past, ABO incompatibility was an absolute contraindication for solid organ transplantation. However, multiple recent trials have suggested strategies for overcoming the reactions between graft antigens and recipient antibodies that cause graft rejection. In this study, we determined the usefulness of plasma exchange (PE) for removing anti-A/B antibodies that cause hyperacute/acute humoral graft rejection in patients undergoing ABO-incompatible kidney transplantation. METHODS: In our study, 12 patients underwent ABO-incompatible kidney transplantation. All recipients received pre-transplantation conditioning by PE or intravenous immunoglobulin (IVIG) administration. After pre-transplantation conditioning, anti-A/B antibody titers were evaluated, and transplantation was performed when the titer was below 1:8. To assess the transplantation outcome, anti-A/B antibody titers, creatinine level, estimated glomerular filtration rate (eGFR), and proteinuria levels were measured. RESULTS: Anti-A/B antibody titers were below 1:8 in all patients at the time of transplantation. eGFR measured on post-transplant day 14 showed that 10 patients had immediate recovery of graft function, while 2 patients had slow recovery of graft function. Short-term outcomes of ABO-incompatible kidney transplantation (measured as creatinine levels) after reducing anti-A/B antibody titers were similar to those of ABO-compatible kidney transplantation. After transplantation, the anti-A/B antibody titers were below 1:8 in 7 patients, but the remaining 5 patients required post-transplantation PE and IVIG treatment to prevent antigen-antibody reactions. CONCLUSIONS: With the increasing demand for kidney donations, interest in overcoming the ABO incompatibility barrier has increased. PE may be an important breakthrough in increasing the availability of kidneys for transplantation.

Trasplante de intestino delgado: estado actual / Small bowel transplantation -an overview-

Antecedentes: El traplante de intestino delgado es una moderna opción terapéutica cuyo objetivo es restablecer la función de absorción en pacientes con síndrome de intestino corto. Las etiologías que provocan esta enfermedad son diversas y difieren según se trate de niños o de adultos. Antes de que pudiera efectuarse este tipo de intervención, el único tratamiento posible para enfermos con síndrome de intestino corto era la alimentación parenteral durante el resto de sus vidas. Objetivo: Describir el estado actual del trasplante de intestino delgado. Diseño: Artículo de actualización. Método: Se describen las indicaciones así como las características de la técnica anestésica y quirúrgica y del período postoperatorio del trasplante de intestino delgado. Conclusiones: El trasplante de intestino delgado es una intervención compleja que se practica sólo en pocos centros mundiales. La cirugía requiere de clampeos totales o parciales de la vena cava y de la aorta, que generan cambios hemodinámicos y metabólicos. Estas modificaciones fisiopatológicas exigen la participación activa del anestesiólogo para el mantenimiento de la homeostasis. Actualmente se han desarrollado esquemas de inmunosupresión que incrementaron la sobrevida de los pacientes. Las complicaciones postoperatorias más frecuentes son la infección y el rechazo.

Procuración multiorgánica y trasplante renal en niños y adolescentes: experiencia con 300 casos / Multiorganic Procurement and kidney trasplantation in children and teenagers: experience with 300 cases

Introducción. Durante los últimso 20 años el progreso en el campo de los trasplantes de órganos ha sido evidente. Objetivo. reportar la experiencia de siete años con Trasplante Renal (TxR) en niños y adolescente en 300 (por ciento) pacientes en una sola Institución, con énfasis en la frecuencia de rechazo crónico. Material y metodología. Análisis por promedio: media ñ 1DS., prueba t de Student (p). De 06/90 a 06/97, 300n recibieron un TxR 177n (59 por ciento) de donador vivo relacionado (DVR) y 123n (41 por ciento) de donador cadáver (CAD)]. Inmunosupresión: triple esquema con azatioprina y prednisona, grupo I: 138n (46) con ciclosporina Sandimmun y grupo II: 162n (54) con Neoral. La procuración en CAD fue sólo renal en 70n (57) y en 53n (43) fue multiorgánica [corazón: 26n (49), hígado: 15n (28), corazón e hígado: 6n (14), corazón y pulmón: 3n (11) y páncreas: 3n (11)]. Preservación: todos los injertos de DVR bajo hipotermia simple, en CAD: 79n (64) en hipotermia simple y 44n (36) en perfusión hipotérmica pulsátil con solución MPS. Todos los riñones se trasplantaron extraperitoneales. Resultados. La supervivencia actuarial para paciente e injerto a uno y cinco años en DVR fue de: 95 por ciento, 92 por ciento, y 93 por ciento, 82 por ciento, y para CAD de: 93 por ciento, 84 por ciento, y 90 por ciento, 65 por ciento, respectivamente. Frecuencia de rechazo agudo < 1 año para DVR y CAD fue 22 por ciento vs. 36 por ciento, respectivamente, p. NS. Pérdida del injerto por rechazo: 54n (18) [DVR 25n (14) vs. CAD 29n (24), p. NS; pero por rechazo crónico fue de 14/25n (56) en grupo I vs. 10/29n (35) en II, p<0.05. Mortalidad hasta 90 días: DVR 14n (8) vs. CAD 15n (12) p<0.05. Se concluye que: (1) el rechazo continúa siendo la principal causa de pérdida del injerto. (2) La supervivencia del injerto y la incidencia de rechazo agudo no fue estadísticamente diferente entre ambos grupos; pero la pérdida del injerto por rechazo crónico fue significativament menor en le grupo II-Neoral. (3) La procuración de órganos extrarrenales es posible efectuarla con éxito en México, confirmándose como alternativa terapéutica en pacientes con enfermedades crónicas terminales

Terapia imunossupressora no transplante cardíaco / Immunotherapy in heart transplantation

A terapia imunossupressora tem por finalidade a diminuiçäo da resposta fisiológica do organismo contra o enxerto, aumentando sua vida útil. A partir da identificaçäo dos mecanismos envolvidos na compatibilidade e resposta imunológica (celular e humoral), tenta-se controlá-los adequadamente, minimizando ou eliminando a rejeiçäo a curto, médio e longo prazos. Säo descritos esquemas terapêuticos, com associaçäo de drogas com mecanismos de açäo complementares, nas doses mais baixas possíveis, visando eito imunossupressor adequado, para manutençäo da vitalidade do enxerto, ao mesmo tempo que se tentam eveitar efeitos colaterais, potencialmente muito deletérios.

Terapéutica con anticuerpos monoclonal como profiláxis de las crisis agudas de rechazo en trasplante renal: labor de enfermería / Therapeutic with monoclonal antibodies like profilaxis of the sharp crisis of denial in renal transplant: work of nursing

Se realiza un estudio prospectivo longitudinal en un universo de 24 pacientes que recibieron trasplante renal de donante cadáver en el servicio de nefrología de Santiago de Cuba en el Hospital Docente Clínico-quirúrgico"Saturnino Lora" del año 1993.El estudio se realizó agrupando los pacientes en dos grupos:el A con 10 pacientes y el B con 14 pacientes utilizando en ambos el mismo anticuerpo monocronal.Sólo se diferenció el tiempo de aplicación obteniendo los siguientes resultados.La incidencia de rechazo agudo en ambos grupos fue menor durante los primeros 30 días, disminuyó la incidencia del número de crisis por pacientes siendo mayor su efectividad en el primer grupo donde se utilizó hasta los 21 días.Los efectos abversos más frecuentes fueron fiebre, broncoespasmo e hipotensión con duración de 2 a 3 días.Las complicaciones sépticas fueron herpes simple e infecciones fúngicas.El anticuerpo monocronal IORT, aumentó la probalidad de supervivencia del injerto y el paciente.La atención de enfermería se comportó según los requerimientos en cada caso ayudando y manteniendo la evolución satisfactria en estos pacientes

ß2 microglobulina (ß2M) sérica na monitorizaçäo do transplante renal / Serum ß2 microglobulin (ß2M) following renal transplantation

Apesar da melhora na sobrevida do enxerto em pacientes transplantados renais, ocorrida nos últimos dez anos, a rejeiçäo continua sendo uma causa importante de perda de enxerto. Vários testes laboratoriais têm sido estudados na tentativa de se identificar um método näo invasivo que possibilite o diagnóstico precoce de rejeiçäo em pacientes transplantados renais. OBJETIVO. Avaliar a utilidade da monitorizaçäo da ß2 microglobulina sérica no período inicial pós-transplante. Métodos. foram estudados em 20 receptores de transplante renal (10 doadores vivos relacionados e 10 doadores cadáveres), o comportamento diário dos níveis séricos da ß2M e correlacionados com a sua evoluçäo clínica e laboratorial. RESULTADOS. Pacientes que apresentaram boa funçäo renal no pós-operatório imediato e näo mostraram rejeiçäo aguda, precocemente, evoluíram com queda dos níveis de ß2M que se estabilizaram em níveis de 3,7 mg/L no 4§ dia pós-transplante. A sensibilidade de ß2M para o diagnóstico de rejeiçäo aguda foi muito boa (87,5 por cento), mas sua especificidade foi baixa (46 por cento). Nos oito pacientes que näo apresentaram boa funçäo renal, inicialmente, a monitorizaçäo dos níveis de ß2M mostrou-se capaz de diferenciar pacientes com necrose tubular aguda (NTA) sem complicaçöes, de portadores de NTA evoluindo com rejeiçäo ou nefrotoxicidade por CSA. Conclusäo. A monitorizaçäo dos níveis séricos de ß2M näo acrescenta benefício nítido para o diagnóstico de rejeiçäo aguda em pacientes com boa funçäo renal inicial. Contudo, em pacientes evoluindo para NTA, esta monitorizaçäo mostrou-se útil para identificar episódios de rejeiçäo aguda e nefrotoxicidade por CSA