Alteracoes vasculares em rins de doadores falecidos retardam a recuperacao da funcao do enxerto apos o transplante renal / Vasculopathy in the kidney allograft at time of transplantation delays recovery of graft function after deceased-donor kidney transplantation

Objetivo: Analisar as características do doador de múltiplos órgãos, incidência e duração da função retardada do enxerto (FRE), e seu impacto na função renal no primeiro ano após o transplante. Métodos: Foi realizado um estudo retrospectivo, unicêntrico, observacional, analisando os transplantes renais com doador falecido realizados em 2010 no nosso serviço. Resultados: A taxa de FRE foi de 68%, com mediana de duração de 12 dias (variação, 1-61 dias). Quarenta e quatro (38%) pacientes apresentaram FRE com 12 ou mais dias de duração (FRE prolongada). A idade média dos doadores foi de 43 ± 13 anos e 37% deles eram hipertensos. Em 59% dos doadores, a causa da morte foi acidente cerebrovascular, e o tempo de isquemia fria (TIF) médio foi de 23 ± 5 horas. Os receptores tinham idade média de 51 ± 15 anos, tempo em diálise de 43 meses (variação, 1-269) e 25% eram sensibilizados (PRA > 0%). No modelo de regressão logística multivariada, a presença de vasculopatia na biópsia de captação foi o único fator de risco independente para o desenvolvimento de FRE prolongada [OR 3,6 IC 95% (1,2-10,2), p = 0,02]. Os pacientes com FRE prolongada apresentaram pior função renal 1 ano após o transplante em comparação com os pacientes sem FRE (SCr 1,7 vs. 1,3 mg/dL, respectivamente, p = 0,03). Conclusão: A presença de vasculopatia na biópsia de captação foi identificada como fator de risco independente para o desenvolvimento de FRE prolongada. A FRE prolongada foi associada com pior função renal no 1º ano após o transplante. .

Objective: The purpose of this study was to evaluate the impact of donor and recipient characteristics on duration of delayed graft function (DGF) and 1-year serum creatinine (SCr), as a surrogate endpoint for allograft survival. Methods: We reviewed 120 first cadaver kidney transplants carried out consecutively at our center to examine the effect on 1-year SCr of the presence and duration of DGF. Results: DGF rate was 68%, with a median duration of 12 days (range, 1-61). Forty-four (38%) patients presented DGF lasting 12 or more days (prolonged DGF group). Mean donor age was 43 ± 13 years, 37% had hypertension and in 59% the cause of brain death was cardiovascular accident. The mean cold ischemia time was 23 ± 5 hours. Twenty-seven (23%) donors were classified as expanded-criteria donors according to OPTN criteria. The mean recipient age was 51 ± 15 years. The recipients median time in dialysis was 43 months (range, 1-269) and 25% of them had panel reactive antibodies > 0%. Patients with prolonged DGF presented higher 1-year SCr in comparison with patients without DGF (1.7 vs. 1.3 mg/dL, respectively, p = 0.03). In multivariate logistic regression analysis, the only significant factor contributing to the occurrence of prolonged DGF was the presence of vascular lesions in the kidney allograft at time of transplantation (HR 3.6, 95% CI 1.2-10.2; p = 0.02). Conclusion: The presence of vasculopathy in the kidney allograft at time of transplantation was identified as an important factor independently associated with prolonged DGF. Prolonged DGF negatively impacts 1-year graft function. .

Protective response in renal transplantation: no clinical or molecular differences between open and laparoscopic donor nephrectomy

OBJECTIVE: Prolonged warm ischemia time and increased intra-abdominal pressure caused by pneumoperitoneum during a laparoscopic donor nephrectomy could enhance renal ischemia reperfusion injury. For this reason, laparoscopic donor nephrectomy may be associated with a slower graft function recovery. However, an adequate protective response may balance the ischemia reperfusion damage. This study investigated whether laparoscopic donor nephrectomy modified the protective response of renal tissue during kidney transplantation. METHODS: Patients undergoing live renal transplantation were prospectively analyzed and divided into two groups based on the donor nephrectomy approach used: 1) the control group, recipients of open donor nephrectomy (n = 29), and 2) the study group, recipients of laparoscopic donor nephrectomy (n = 26). Graft biopsies were obtained at two time points: T-1 = after warm ischemia time and T+1 = 45 minutes after kidney reperfusion. The samples were analyzed by immunohistochemistry for the Bcl-2 and HO-1 proteins and by real-time polymerase chain reaction for the mRNA expression of Bcl-2, HO-1 and vascular endothelial growth factor. RESULTS: The area under the curve for creatinine and delayed graft function were similar in both the laparoscopic and open groups. There was no difference in the protective gene expression between the laparoscopic donor nephrectomy and open donor nephrectomy groups. The protein expression of HO-1 and Bcl-2 were similar between the open and laparoscopic groups. Furthermore, the gene expression of B-cell lymphoma 2 correlated with the warm ischemia time in the open group (p = 0.047) and that of vascular endothelial growth factor with the area under the curve for creatinine in the laparoscopic group (p = 0.01). CONCLUSION: The postoperative renal function and protective factor expression were similar between laparoscopic ...

The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short- and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T- and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (LuminexH), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed ''de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

Análise de 10 anos de seguimento de transplantesrenais com doador vivo não aparentado / Ten-year follow-up of kidney transplantation with living unrelated donor

INTRODUÇÃO: No contexto atual da elevada escassez de órgãos para o transplante renal e do reconhecimento cada vez maior da rejeição crônica mediada por anticorpos anti-HLA como uma importante causa de perda do enxerto, uma contínua demonstração da boa evolução a longo prazo de transplantes renais com doadores vivos não aparentados (DVNA) é de suma importância. OBJETIVOS: Analisar a sobrevida do enxerto e dos pacientes transplantados com DVNA, e compará-la com doadores vivos aparentados (DVA). MÉTODOS: Foram analisados 389 primeiros transplantes renais com doador vivo realizados em um único centro, entre janeiro de 1998 e dezembro de 2007, 281 com DVA e 108 com DVNA. RESULTADOS: Não houve diferença significativa na sobrevida dos pacientes (89,1 por cento vs. 84,7 por cento, p = 0,40) e do enxerto (81,1 por cento vs. 68,9 por cento, p = 0,77), em 10 anos de seguimento, entre DVA e DVNA, respectivamente. Na análise multivariada do modelo de regressão proporcional de Cox, a reatividade contra painel (PRA) > 10 por cento e a ocorrência de rejeição aguda no 1º ano após o transplante foram os únicos preditores independentes de perda do enxerto (OR 2,54, IC 95 por cento 1,35 - 4,78; p < 0,05 e OR 4,1, IC 95 por cento 2,04 -4,78; p < 0,05, respectivamente). CONCLUSÃO: Transplantes renais com DVNA representam uma importante fonte de órgãos para suprir uma crescente demanda, com resultados semelhantes aos transplantes com DVA, independente da compatibilidade HLA.

INTRODUCTION: In the current era of scarcity of kidneys available for transplantation, and chronic anti-HLA-mediated rejection as a main cause of graft loss, continuous demonstration of the long-term survival of grafts from living unrelated kidney donors (LURD) is paramount. OBJECTIVE: Analyze long-term kidney graft and patient outcomes using LURD, and compare them with living related donors (LRD). METHODS: We analyzed the 389 first renal transplantations performed with a living donor (281 LRD and 108 LURD), in a single center, from January 1998 through December 2007. RESULTS: There were no significant differences between LRD and LURD as refers to patient survival (89.1 percent vs. 84.7 percent, p = 0.40, respectively) and graft survival (81.1 percent vs. 68.9 percent, p = 0.77, respectively), 10 years post-transplantation. On Cox proportional regression model of multivariate analysis, panel reactive antibodies (PRA) > 10 percent and the occurrence of acute rejection in the first year posttransplantation were the only independent predictors of graft loss (HR 2.54, 95 percent CI 1.35 -4.78; p < 0.05 and HR 4.1, 95 percent CI 2.04 - 4.78; p < 0.05, respectively). CONCLUSION: LURD are an important source of organs for renal transplantation, with results similar to those obtained with LRD, regardless of HLA matching.