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      ¿Ha mejorado la supervivencia del injerto tras el trasplante renal en la era de la moderna inmunosupresión? Translated title: Has the survival of the graft improved after renal transplantation in the era of modern immunosuppression?

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          Abstract

          Durante los últimos años, la introducción de nuevos fármacos inmunosupresores ha permitido reducir la tasa de rechazo agudo y mejorar de forma muy significativa los resultados del trasplante renal a corto plazo. Sin embargo, esta mejoría no se ha traducido en cambios tan significativos en los resultados a largo plazo, de tal forma que el fracaso tardío del injerto sigue siendo una causa frecuente de reingreso en programas de diálisis y de reentrada en la lista de espera. Múltiples agresiones de origen inmune y no inmune actúan de forma conjunta y conducen a la disfunción crónica del injerto. Las características del órgano implantado son un determinante mayor de la supervivencia del injerto y, aunque se han diseñado diversos algoritmos para conocer el riesgo del órgano a trasplantar y poderlo asignar al receptor más adecuado, su aplicación en la clínica es todavía excepcional. Por otra parte, caracterizar en cada paciente los factores inmunes (rechazo clínico y subclínico, reactivación de infecciones virales latentes, adherencia al tratamiento) y no inmunes (hipertensión, diabetes, anemia, dislipemia) que contribuyen a la disfunción crónica del injerto puede permitirnos intervenir de forma eficaz para retrasar la progresión de este proceso. Por lo tanto, identificar las causas de fracaso del injerto y sus factores de riesgo, aplicar modelos predictivos e intervenir sobre los factores causales pueden ser algunas de las estrategias para mejorar los resultados de trasplante renal en términos de supervivencia. En esta revisión se analizan algunas de las evidencias que condicionan el fracaso del injerto, así como los aspectos terapéuticos y pronósticos relacionados con este: 1) Magnitud del problema y causas de fracaso del injerto; 2) Identificación de los factores de riesgo de fracaso del injerto; 3) Estrategias terapéuticas para disminuir el fracaso del injerto; y 4) Predicción del fracaso del injerto.

          Translated abstract

          The introduction of new immunosuppressant drugs in recent years has allowed for a reduction in the acute rejection rate along with highly significant improvements in short-term renal transplantation results. Nonetheless, this improvement has not translated into such significant changes in the longterm results. In this way, late graft failure continues to be the frequent cause of readmission onto dialysis programmes and re-entry onto the waiting list. Multiple insults of immune and non-immune origin act together and lead to chronic graft dysfunction. The characteristics of the transplanted organ are a greater determinant of graft survival and although various algorithms have been designed as a way of understanding the risk of the transplant organ and thus assign the most adequate receptor, its clinical application still only occurs in exceptional circumstances. Meanwhile, characterising, for each patient, the immune factors (clinical and subclinical rejection, reactivation of dormant viral infections, adherence to treatment) and non-immune factors (hypertension, diabetes, anaemia, dyslipidaemia) that contribute to chronic graft dysfunction could allow us to intervene more effectively as a way of delaying the progress of such process. Therefore, identifying the causes of graft failure and its risk factors, applying predictive models and intervening in causal factors could constitute some of the strategies for improving renal transplantation results in terms of survival. This review analyses some of the evidences conditioning graft failure as well as related therapeutic and prognostic aspects: 1) magnitude of the problem and causes of graft failure; 2) identification of graft failure risk factors; 3) therapeutic strategies for reducing graft failure, and; 4) graft failure prediction.

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          The natural history of chronic allograft nephropathy.

          With improved immunosuppression and early allograft survival, chronic allograft nephropathy has become the dominant cause of kidney-transplant failure. We evaluated the natural history of chronic allograft nephropathy in a prospective study of 120 recipients with type 1 diabetes, all but 1 of whom had received kidney-pancreas transplants. We obtained 961 kidney-transplant-biopsy specimens taken regularly from the time of transplantation to 10 years thereafter. Two distinctive phases of injury were evident as chronic allograft nephropathy evolved. An initial phase of early tubulointerstitial damage from ischemic injury (P<0.05), prior severe rejection (P<0.01), and subclinical rejection (P<0.01) predicted mild disease by one year, which was present in 94.2 percent of patients. Early subclinical rejection was common (affecting 45.7 percent of biopsy specimens at three months), and the risk was increased by the occurrence of a prior episode of severe rejection and reduced by tacrolimus and mycophenolate therapy (both P<0.05) and gradually abated after one year. Both subclinical rejection and chronic rejection were associated with increased tubulointerstitial damage (P<0.01). Beyond one year, a later phase of chronic allograft nephropathy was characterized by microvascular and glomerular injury. Chronic rejection (defined as persistent subclinical rejection for two years or longer) was uncommon (5.8 percent). Progressive high-grade arteriolar hyalinosis with luminal narrowing, increasing glomerulosclerosis, and additional tubulointerstitial damage was accompanied by the use of calcineurin inhibitors. Nephrotoxicity, implicated in late ongoing injury, was almost universal at 10 years, even in grafts with excellent early histologic findings. By 10 years, severe chronic allograft nephropathy was present in 58.4 percent of patients, with sclerosis in 37.3 percent of glomeruli. Tubulointerstitial and glomerular damage, once established, was irreversible, resulting in declining renal function and graft failure. Chronic allograft nephropathy represents cumulative and incremental damage to nephrons from time-dependent immunologic and nonimmunologic causes. Copyright 2003 Massachusetts Medical Society
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            Long-term renal allograft survival in the United States: a critical reappraisal.

            Renal allograft survival has increased tremendously over past decades; this has been mostly attributed to improvements in first-year survival. This report describes the evolution of renal allograft survival in the United States where a total of 252 910 patients received a single-organ kidney transplant between 1989 and 2009. Half-lives were obtained from the Kaplan-Meier and Cox models. Graft half-life for deceased-donor transplants was 6.6 years in 1989, increased to 8 years in 1995, then after the year 2000 further increased to 8.8 years by 2005. More significant improvements were made in higher risk transplants like ECD recipients where the half-lives increased from 3 years in 1989 to 6.4 years in 2005. In low-risk populations like living-donor-recipients half-life did not change with 11.4 years in 1989 and 11.9 years in 2005. First-year attrition rates show dramatic improvements across all subgroups; however, attrition rates beyond the first year show only small improvements and are somewhat more evident in black recipients. The significant progress that has occurred over the last two decades in renal transplantation is mostly driven by improvements in short-term graft survival but long-term attrition is slowly improving and could lead to bigger advances in the future. ©2010 The Authors Journal compilation©2010 The American Society of Transplantation and the American Society of Transplant Surgeons.
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              Identifying specific causes of kidney allograft loss.

              The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 +/- 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                nefrologia
                Nefrología (Madrid)
                Nefrología (Madr.)
                Sociedad Española de Nefrología (Cantabria, Santander, Spain )
                0211-6995
                1989-2284
                2013
                : 33
                : 1
                : 14-26
                Affiliations
                [01] Barcelona orgnameHospital Universitari Vall d'Hebron orgdiv1Servicio de Nefrología
                [02] Málaga orgnameHospital Regional Universitario Carlos Haya orgdiv1Servicio de Nefrología
                Article
                S0211-69952013000100003
                10.3265/Nefrologia.pre2012.Oct.11739
                23364624
                ad561d2d-17c7-4c3b-b43b-9fe8ad0d6ad2

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

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                Figures: 0, Tables: 0, Equations: 0, References: 96, Pages: 13
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                Trasplante renal,Supervivencia del injerto,Inmunosupresión,Rechazo agudo,Rechazo crónico,Renal transplantation,Graft survival,Immunosuppression,Acute rejection,Chronic rejection

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