Anatomía patológica y Nefrología / Anatomic pathology and nephrology

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Criterios diagnósticos de rechazo mediado por anticuerpos en el trasplante renal / Diagnostic criteria of antibody-mediated rejection in kidney transplants

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Diagnostic criteria of antibody-mediated rejection in kidney transplants.

The diagnosis and treatment of anti-donor antibody-mediated rejection or humoral rejection (ABMR) is one of the main discussions at the moment in kidney transplantation. The search for histopathological markers that help us to diagnose ABMR has been more problematic, in contrast to the histological expression of cellular or tubulointerstitial rejection. Although the relationship between post-transplant anti-donor antibodies and the allograft's prognosis has been a topic of discussion for a long time, led in the main by P.Terasaki, it was not until the beginning of 1990s when P. Halloran studied the humoral mechanisms of rejection in greater depth. Feutch described the importance of C4d deposits as a marker that shows a humoral mechanism of allograft rejection in 1993. As a result of many studies carried out, the Banff consensus group established some diagnostic histopathological criteria of acute (ABMR) in 2003. These have been modified slightly in later meetings of the group. Furthermore, in 2005 this same working group looked at the physiopathological mechanisms causing chronic allograft failure in more detail and established the criteria defining chronic humoral rejection. In this review, we are trying to update any useful histopathological criteria for diagnosing acute and chronic ABMR.

Patología crónica del injerto renal / No disponible

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Recomendaciones para la indicación, obtención, procesamiento y evaluación de biopsias en el trasplante renal / No disponible

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Banff schema for grading pancreas allograft rejection: working proposal by a multi-disciplinary international consensus panel.

Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients.

[Renal xenotransplant. Acute vascular rejection]. / Xenotrasplante renal. El rechazo vascular agudo.

INTRODUCTION AND OBJECTIVES: Organ transplant is nowadays a usual and succesful practice, although with limited application due to the lack of organs. Yearly thousands of patients get access to the waiting list and finally will death while they are waiting for an organ. In the U.S.A., 2005 waiting list for kidneys, heart, liver lung and pancreas was around 94.419. Number of transplants performed was 27.966 and died patients while waiting for an organ, 41.392 (1). Pig xenotransplant is one of the possibilities to ameliorate the lack of organs for transplant. Arrangement of pigs with different genetic modifications generated great expectatives on the use of these organs in clinics. Although preclinical experimental studies with kidneys reached prolonged survivals, these are really insufficient to go on with the clinical appliance. Hyperacute rejection produces destruction of the organ immediately. This problem could be pharmacologically precluded in xeno-transplant. However, acute rejection or vascular rejection usually produces the lost of the implant. New inmunosuppresive schedules delay significantly rejection, but not definitively. Xenotransplant as a therapeutic option introduces important scientific problems, as well as ethical and social. This paper reports a summary of our experience in renal xenotransplant and the management of acute rejection. MATERIAL AND METHODS: Twenty xenotransplants from transgenic pig (hDAF) as donor to babuine as receptor. Average weight of the animals ranged 11.4-75 kgrs and babuines 10-26 kg. Xenograft average weight ranged 39-160 grs. Implant was performed to aorta and cava. Four inmunosupressive schedules were used. RESULTS: Average survival was 7-9 days. Final Histological findings are described. Changes observed were secondary to acute tubular necrosis mixed with changes due to acute rejection. Three grafts were lost due to technical major problems. CONCLUSIONS: Although we have observed some promising results, xenotransplant is a very difficult problem to solve in the long-term. A lot of research is still needed-.

Xenotrasplante renal. El rechazo vascular agudo / Renal xenotransplant. Acute vascular rejection

Introducción y objetivos: El trasplante de órganos es hoy una práctica habitual y de éxito, pero de aplicación limitada, debido a la insuficiencia de órganos. Anualmente miles de pacientes en lista de espera fallecen, esperando un órgano. En EEUU en el 2005 la lista de espera para trasplantes de órganos, riñón, corazón, hígado, pulmón, páncreas era de 94.419. El número de trasplantes realizados fue de 27.966 y el de fallecidos esperando un órgano 41.392. (1) El xenotrasplante de órganos de cerdo es una de las esperanzas para aliviar la falta de órganos para el trasplante. La disponibilidad de cerdos con distintas modificaciones genéticas, creó grandes expectativas sobre una pronta utilización clínica de los mismos, sin embargo, aunque los estudios experimentales preclínicos con el riñón han alcanzado supervivencias prolongadas, estas son insuficientes para dar el paso a la fase clínica. El rechazo hiperagudo (RH) con destrucción del órgano de forma inmediata, habitual en el trasplante de órganos entre especies distintas filogenéticamente (trasplante discordante) puede en la actualidad ser evitado sin embargo, la aparición de un posterior rechazo humoral agudo (RHA) también llamado rechazo vascular agudo (RVA) o xenorechazo agudo retardado, da lugar al fracaso del xenotrasplante. La utilización de distintas pautas de inmunosupresión han conseguido retrasar de forma significativa este rechazo, pero no lo previenen de forma sistemática. El xenotrasplante como opción terapéutica plantea importantes problemas científicos, éticos y sociales. En este artículo exponemos un resumen de nuestra experiencia en xenotrasplante renal y comentamos los problemas del RVA. Material y método: Se han practicado 20 xenotrasplantes renales de cerdo transgénico hDAF (donante) a babuino (receptor). El peso de los cerdos osciló entre 11,400 y 75 kg. y el de los babuinos entre 10 y 26,500 kg. El peso del xenoinjerto, riñón del cerdo, osciló entre 39 y 160 g. Resultados: La supervivencia media de los animales estuvo entre 7-9 días. El estudio histológico final de los injertos mostró cambios secundarios a necrosis tubular aguda mezclados con alteraciones propias de rechazo agudo. Tres injertos se perdieron por problemas técnicos mayores. Conclusiones: Aunque hemos observado resultados prometedores, el xenotrasplante es una cuestión de gran dificultad, especialmente a largo plazo. Se precisa aún en la actualidad de mucha actividad investigadora en este campo

Introduction and objectives: Organ transplant is nowadays a usual and succesful practice, although with limited application due to the lack of organs. Yearly thousands of patients get access to the waiting list and finally will death while they are waiting for an organ. In USA, 2005 waiting list for kidneys, heart, liver lung and pancreas was around 94.419. Number of transplants performed was 27.966 and died patients while waiting for an organ, 41.392 (1). Pig xenotransplant is one of the possibilities to ameliorate the lack of organs for transplant. Arrangement of pigs with different genetic modifications generated great expectatives on the use of these organs in clinics. Although preclinical experimental studies with kidneys reached prolonged survivals, these are really insufficient to go on with the clinical appliance. Hyperacute rejection produces destruction of the organ immediately. This problem could be pharmacologically precluded in xenotransplant. However, acute rejection or vascular rejection usually produces the lost of the implant. New inmunosuppresive schedules delay significantly rejection, but not definitively. Xenotransplant as a therapeutic option introduces important scientific problems, as well as ethical and social. This paper reports a summary of our experience in renal xenotransplant and the management of acute rejection. Material and methods: Twenty xenotransplants from transgenic pig (hDAF) as donor to babuine as receptor. Average weight of the animals ranged 11.4-75 kgrs and babuines 10-26 kg. Xenograft average weight ranged 39-160 grs. Implant was performed to aorta and cava. Four inmunosupressive schedules were used. Results: Average survival was 7-9 days. Final Histological findings are described. Changes observed were secondary to acute tubular necrosis mixed with changes due to acute rejection. Three grafts were lost due to technical major problems. Conclusions: Although we have observed some promising results, xenotransplant is a very difficult problem to solve in the long-term. A lot of research is still needed

Papel del patólogo en la nefrología / The rol of the pathologist in nephrology

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Nefropatía lúpica (NL): valor de la biopsia / Lupus nephritis: the value of biopsy

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Patología renal glomerular y VHC / Glomerular pathology and HCV

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[Association between membranous glomerulonephritis and Crohn's disease]. / Asociación de glomerulonefritis membranosa y enfermedad de Crohn.

We report the case of a 37 year old man who suffered from Crohn's Disease (CD), and was receiving treatment with mesalazine (5-ASA). Nine years after the diagnosis, because of detecting a slight proteinuria, a renal biopsy is made, being the anatomo-pathologic result compatible with membranous glomerulonephritis (MGN). Checking previous literature we have only found two cases reported of MGN in coincidence with Inflammatory Bowel Disease (IBD), one in association with Ulcerative Colitis and the other with Crohn's Disease in a 12 years old boy. This is, therefore, the second case presenting MGN associated with CD and the first in an adult patient.

[Renal xenotransplantation from hDAF pig to baboon. Experience and review]. / Xenotrasplante renal cerdo hDAF-babuino. Experiencia y revisión.

UNLABELLED: The renal xenotransplant could be the solution on the demand of organs for transplantation. We present here our experience and review the actual status of the xenotransplant. METHODS: We have done 20 xenotransplants from transgenic pig h DAF to baboons, with four protocols of immunosuppression. All the hosts were treated with GAS 914. Group A: Cyclophosphamide, Cyclosporine, Mycophenolate, and Steroids (n = 10). Group B: Cyclophosphamide, Cyclosporine, FTY 720, and Steroids (n = 3). Group C: Basiliximab, Cyclosporine, Mycophenolate, and Steroids (n = 3). Group D: Basiliximab, FTY 720, Everolymus, and Steroids (n = 4). RESULTS: The duration of the xenografts ranged between 1 and 31 days. The function of the xenografts in relation to the type of immunosuppression were not significantly different: A) 7 days, B) 8 days, C) 8 days, and D) 9 days. CONCLUSIONS: 1. The cold ischemic time of the graft, has influence in the initial function of the kidneys but not in the evolution and duration of the graft. 2. The hyperacute rejection has been overcome with the utilization of transgenic pigs. The graft failure was due to acute humoral rejection that was not aborted by the actual inmunosupressors. 3. It is necessary to develop new immunosuppression protocols, through new knowledge of their pharmacology and the physiology of the xenografts, and at the same time it is important to avoid the potential risk of transmission of animal infections.

Influence of the management of asystolic donors on kidney transplantation outcome.

Two methods of donor management were analysed, namely, with and without in situ cooling perfusion of the kidney in an attempt to determine the optimal management and preservation methods for asystolic kidney donors. The group of recipients of in situ cooling perfusion kidneys showed more days of oliguria (P <.05), needed more dialysis sessions (P <.05), and showed no transplant function during the first week after surgery. This group also had a greater probability of acute rejection (P =.071) and a higher rate of nonfunctioning grafts (P =.09). We conclude that in situ cooling perfusion of asystolic kidney donors impairs graft function.

Histological features with clinical impact in chronic allograft nephropathy: review of 66 cases.

UNLABELLED: The histological features of chronic allograft nephropathy (CAN) are variable, since it is related to multiple donor and recipient factors. The main histological parameters in CAN are interstitial fibrosis, tubular atrophy, chronic vasculopathy and glomerulosclerosis. There have been many attempts to relate chronic deterioration of renal function with histologic features. MATERIALS AND METHODS: We reviewed 66 kidney transplant patients (43 men/23 women) with renal failure 6 months after transplant. The clinical data included donor and recipient age, cold ischemia time, delayed graft function (DGF), creatinine clearance, proteinuria, HLA compatibility, CMV infection, cholesterol levels, diastolic and systolic blood pressure. Banff criteria were used to grade histological parameters. The relation between clinical and histological data were analyzed using chi square, Student t, Mann Whitney and Kruskal-Wallis tests as appropriate. The cumulative graft and patient survival rates were calculated by the Kaplan-Meier method. RESULTS: The survival rate of patients with creatinine clearances >3 mg/dL at the time of the biopsy was worse than that of patients with creatinine <3 mg/dL (P =.001; log rank 20.1). We found an association between the grade of arteriosclerosis and the diastolic blood pressure (P =.017). The creatinine level was greater among patients with tabulitis than those without tubulitis (P =.06). In addition to our results we review the literature especially related to the histological feature of CAN in an attempt to detect histological findings predictive of the long term outcome of kidney allografts.

Severe cardiac allograft dysfunction without endomyocardial biopsy signs of cellular rejection: incidence and management.

Acute dysfunction of cardiac allograft without evidence of cellular rejection is a potentially fatal complication of heart transplantation that suggests a humoral origin. In clinical practice, humoral rejection (HR) is suspected when there is evidence of severe allograft dysfunction but endomyocardial biopsy (EMB) shows no evidence of cellular rejection. Between April 1991 and August 2003, 12 patients (2.74%) among 438 heart transplants displayed this condition. Time post-heart transplant (HT) was 21.3 +/- 24.7 months (range 2 to 72 months). Immunofluorescence studies using classic markers were negative. All patients were treated with methylprednisolone "bolus" and plasmapheresis until clinical recovery, after which their immunosuppressive regimens were modified. Eleven of the 12 patients recovered satisfactory allograft function. In this series the incidence of suspected HR was low. Unlike other studies, we observed HR not only soon but also even years after HT. Plasmapheresis seems to be an effective treatment.