Different induction therapies for kidney transplantation with living donor.

INTRODUCTION: Indications for induction therapy is not consensual in living donors. OBJECTIVE: The objective of this study was compare no induction with thymoglobulin and basiliximab induction in the incidence of acute rejection in kidney transplantation with living donor. METHODS: We select all cases of renal transplantation with living donor performed in Hospital das Clínicas de Botucatu da UNESP during the period of January 2010 to December 2013. The group was divided by the type of medication used for induction. RESULTS: A total of 90 patients were evaluated. There were no differences in baseline characteristics of age and underlying disease. The rate of biopsy-proven acute rejection was higher in the group without induction (42.9%) compared to basiliximab group (20%) and Thymoglobulin (16.7%), p = 0.04. The rejection by compatibility shows that the identical had the lower rejection rate (10%). The haploidentical group without induction had the highest rejection rates (53.3%). In all distinct group the rejection rates were similar with basiliximab or Thymoglobulin, p = NS. The use of induction therapy was associated independently with a lower risk of rejection (OR = 0.32 CI: 0.11 to 0.93, p = 0.036). There were no differences in renal function at 6 months and patient survival and graft in the three groups. DISCUSSION: The haploidentical patients without induction were those with higher rates of acute rejection. The group of patients induced with Thymoglobulin had a higher immunological risk, however showed low rates of rejection. CONCLUSION: The use of induction therapy resulted in lower rates of rejection in transplantation with living donor.

Diferentes esquemas de indução para transplante renal com doador vivo / Different induction therapies for kidney transplantation with living donor

Resumo Introdução: A indicação de terapia de indução não é consensual em doadores vivos. Objetivo: Comparar não indução com indução com basiliximab e timoglobulina na incidência de rejeição aguda em transplante renal com doador vivo. Métodos: Todos os casos de transplante renal com doador vivo realizados no serviço de transplante do Hospital das Clínicas de Botucatu da UNESP no período de janeiro de 2010 a dezembro de 2013. O grupo foi dividido pelo tipo de medicação usada na indução. Resultados: Foram avaliados 90 pacientes. Não houve diferenças nas características basais de idade e doença de base. A taxa de rejeição aguda comprovada por biópsia foi maior no grupo sem indução (42,9%) em comparação aos grupos basiliximab (20%) e timoglobulina (16,7%), p = 0,04. A divisão das rejeições por compatibilidade mostra que os idênticos apresentaram menor taxa de rejeição (10%). O grupo haploidêntico sem indução apresentou as maiores taxas de rejeição (53,3%). No grupo distinto, todos foram induzidos e as taxas de rejeição foram semelhantes com basiliximab ou timoglobulina, p = NS. O uso de terapia de indução associou-se de forma independente a menor risco de rejeição (OR = 0,32 IC: 0,11-0,93, p = 0,036). Não houve diferenças na função renal aos 6 meses e sobrevida do paciente e enxerto nos três grupos. Discussão: Os pacientes haploidênticos sem indução foram os que apresentaram maiores taxas de rejeição aguda. O grupo de pacientes induzidos com timoglobulina apresentava maior risco imunológico, entretanto, eles mostraram baixas taxas de rejeição. Conclusão: O uso de terapia de indução resultou em menores taxas de rejeição em transplante com doador vivo. .

Abstract Introduction: Indications for induction therapy is not consensual in living donors. Objective: The objective of this study was compare no induction with thymoglobulin and basiliximab induction in the incidence of acute rejection in kidney transplantation with living donor. Methods: We select all cases of renal transplantation with living donor performed in Hospital das Clínicas de Botucatu da UNESP during the period of January 2010 to December 2013. The group was divided by the type of medication used for induction. Results: A total of 90 patients were evaluated. There were no differences in baseline characteristics of age and underlying disease. The rate of biopsy-proven acute rejection was higher in the group without induction (42.9%) compared to basiliximab group (20%) and Thymoglobulin (16.7%), p = 0.04. The rejection by compatibility shows that the identical had the lower rejection rate (10%). The haploidentical group without induction had the highest rejection rates (53.3%). In all distinct group the rejection rates were similar with basiliximab or Thymoglobulin, p = NS. The use of induction therapy was associated independently with a lower risk of rejection (OR = 0.32 CI: 0.11 to 0.93, p = 0.036). There were no differences in renal function at 6 months and patient survival and graft in the three groups. Discussion: The haploidentical patients without induction were those with higher rates of acute rejection. The group of patients induced with Thymoglobulin had a higher immunological risk, however showed low rates of rejection. Conclusion: The use of induction therapy resulted in lower rates of rejection in transplantation with living donor. .

The role of renin-angiotensin system in the chronic allograft nephropathy: an immunohistochemical study.

BACKGROUND: Evidences suggest a role of renin-angiotensin system (RAS) in the development of chronic allograft injury. METHODS: We correlated intrarenal angiotensin-converting enzyme, angiotensin II (Angio II) and transforming growth factor ß1 (TGFß1) expression in 58 biopsies-proven chronic allograft nephropathy (CAN) with tissue injury and allograft survival. RESULTS: The biopsies with CAN were graded according to Banff classification as I (22 cases), II (17) and III (19); 27 biopsies also showed a mononuclear inflammatory infiltrate in scarred areas. There were increased expression of angiotensin converting-enzyme (ACE), Angio II and TGFß1 mainly in tubulointerstitial compartment in the group with CAN; there was no association of Angio II and TGFß1 expression with interstitial fibrosis. There were no significant differences of ACE, Angio II and TGFß1 expression between the patients treated and untreated with RAS blockade, and with the graft outcome. Interstitial inflammatory infiltrate had positive correlation with interstitial fibrosis and significant impact on graft survival at 8 years. CONCLUSIONS: Our study showed in a group of cases with CAN a high percentage of inflammatory infiltrate that correlated with interstitial fibrosis and graft outcome. The chronic inflammatory changes in these cases did not show significant association with local RAS expression.

Quantified power Doppler as a predictor of delayed graft function after renal transplantation.

PURPOSE: No safe ultrasound (US) parameters have been established to differentiate the causes of graft dysfunction. OBJECTIVES: To define US parameters and identify the predictors of normal graft evolution, delayed graft function (DGF), and rejection at the early period after kidney transplantation. METHODS: Between June 2012 and August 2013, 79 renal transplant recipients underwent US examination 1-3 days posttransplantation. Resistive index (RI), power Doppler (PD), and RI + PD (quantified PD) were assessed. Patients were allocated into three groups: normal graft evolution, DGF, and rejection. RESULTS: Resistive index of upper and middle segments and PD were higher in the DGF group than in the normal group. ROC curve analysis revealed that RI + PD was the index that best correlated with DGF (cutoff = 0.84). In the high RI + PD group, time to renal function recovery (6.33 ± 6.5 days) and number of dialysis sessions (2.81 ± 2.8) were greater than in the low RI + PD group (2.11 ± 5.3 days and 0.69 ± 1.5 sessions, respectively), p = 0.0001. Multivariate analysis showed that high donor final creatinine with a relative risk (RR) of 19.7 (2.01-184.7, p = 0.009) and older donor age (RR = 1.17 (1.04-1.32), p = 0.007) correlated with risk DGF. CONCLUSIONS: Quantified PD (RI + PD) was the best DGF predictor. PD quantification has not been previously reported.

The 600 kidney transplants performed at the Botucatu Medical School Hospital - UNESP: changes over.

INTRODUCTION: A progressive improvement in kidney transplant outcomes has been achieved over the last decades. OBJECTIVE: To determine the degree to which this has occurred in our center, we conducted an outcome analysis of our kidney transplant program during three different time periods, especially focusing on patient and graft survival. METHODS: The 600 kidney transplants performed at Botucatu Medical School/UNESP up to December 2011 were examined. Three different time periods were chosen to correspond with major shifts in immunosuppressant usage: Era 1 (1987-2000), cyclosporine and azathioprine usage (n = 180); Era 2 (2001-2006), cyclosporine and mycophenolate mofetil usage (n = 120); and Era 3 (2007-2011), tacrolimus and mycophenolate (n = 300). RESULTS: Compared with the first era, mean recipient age, diabetes prevalence, and the number of living donor transplantations (60%) were increased in the third era. Induction therapy was used in 75% of the cases in Era 3, 46.6% in Era 2, and in 3.9% in Era 1 (p < 0.0001). The mean number of transplants/year rose from 14 in Era 1 to 75 in Era 3. Overall survival according to donor type was similar to that reported in the literature. Five-year graft survival following deceased donor transplantation progressively increased from 13.1% (Era 1) to 81.9% (Era 3). CONCLUSION: Significant differences were observed over time. The percentage of living donors decreased as that of deceased donors increased. Survival after deceased donor transplants was greatest in Era 3, probably due to the improved experience of the medical team, and to the use of tacrolimus and mycophenolate mofetil combination with induction.

Os 600 transplantes renais do Hospital das Clínicas da Faculdade de Medicina de Botucatu (HC da FMB) - UNESP: Mudanças ao longo do tempo / The 600 kidney transplants performed at the Botucatu Medical School Hospital - UNESP: Changes over

Introdução: Os resultados alcançados pelos transplantes renais nas últimas décadas têm melhorado progressivamente. Objetivo: A fim de determinar a extensão desse progresso, conduzimos uma análise dos resultados obtidos em nosso programa de transplantes através de três períodos diferentes. Métodos: Avaliamos os 600 transplantes renais realizados no HC FMB-UNESP até dezembro de 2011, subdividindo-os em três eras, de acordo com a imunossupressão vigente. Era 1: de 1987 a 2000 (n = 180); associação de ciclosporina e azatioprina. Era 2: de 2001 a 2006 (n = 120); associação de ciclosporina e micofenolato e Era 3: de 2007 a 2011 (n = 300); associação de tacrolimus e micofenolato. Resultados: Os resultados mostram aumento da idade média do receptor, da prevalência de diabetes e do número de transplantes com doador falecido (60%) na terceira era. O uso de terapia de indução foi de 75% era atual contra 46,6% (Era 2) e 3,9% (Era 1), p < 0,0001. Os dados de sobrevida geral por tipo de doador mostram dados semelhantes à literatura. Houve progressivo aumento da sobrevida do enxerto com doadores falecidos em 5 anos, saindo de 13,7% (Era 1) para 81,9% (Era 3). Conclusão: Houve significativas diferenças ao longo do tempo, culminando com aumento do volume de transplantes na atual era (média de 14 transplantes/ano na Era 1 para 75 transplantes/ano na Era 3). Inverteu-se o perfil de transplantes na era atual com predomínio de doador falecido. A melhor sobrevida com doador falecido da atual era foi atribuída a maior experiência do centro e aos esquemas de imunossupressão baseados na combinação de tacrolimus com micofenolato associados a esquema de indução. .

Introduction: A progressive improvement in kidney transplant outcomes has been achieved over the last decades. Objective: To determine the degree to which this has occurred in our center, we conducted an outcome analysis of our kidney transplant program during three different time periods, especially focusing on patient and graft survival. Methods: The 600 kidney transplants performed at Botucatu Medical School/UNESP up to December 2011 were examined. Three different time periods were chosen to correspond with major shifts in immunosuppressant usage: Era 1 (1987-2000), cyclosporine and azathioprine usage (n = 180); Era 2 (2001-2006), cyclosporine and mycophenolate mofetil usage (n = 120); and Era 3 (2007-2011), tacrolimus and mycophenolate (n = 300). Results: Compared with the first era, mean recipient age, diabetes prevalence, and the number of living donor transplantations (60%) were increased in the third era. Induction therapy was used in 75% of the cases in Era 3, 46.6% in Era 2, and in 3.9% in Era 1 (p < 0.0001). The mean number of transplants/year rose from 14 in Era 1 to 75 in Era 3. Overall survival according to donor type was similar to that reported in the literature. Five-year graft survival following deceased donor transplantation progressively increased from 13.1% (Era 1) to 81.9% (Era 3). Conclusion: Significant differences were observed over time. The percentage of living donors decreased as that of deceased donors increased. Survival after deceased donor transplants was greatest in Era 3, probably due to the improved experience of the medical team, and to the use of tacrolimus and mycophenolate mofetil combination with induction. .

Mononuclear inflammatory infiltrate and microcirculation injury in acute rejection: role in renal allograft survival.

This study aimed at investigating associations between monocytes/macrophages (Mo) infiltration and three important criteria associated with acute antibody-mediated rejection: C4d staining, microcirculation injury, and graft survival time. By quantitative analysis, Mo were counted in peritubular capillaries and in the interstitial compartment (peritubular/interstitial Mo), and they were also identified in glomeruli (glomerular Mo). The study included 47 patients who received renal allograft between 1991 and 2009. Capillaritis and glomerulitis were classified by the Banff scoring system, and C4d and Mo were analyzed by immunohistochemistry. In the quantitative analysis, the mean values of 50 Mo per 10 high-power fields (HPF) and 4 Mo per glomerulus were used as cut-off points for the peritubular/interstitial and glomerular compartments, respectively. Positive C4d cases were associated with the groups of biopsies with a mean value ≥50 Mo per 10 HPF (p = 0.01) and ≥4 Mo per glomerulus (p = 0.02). The group with a mean value ≥4 Mo per glomerulus also showed association with the presence of glomerulitis (p = 0.02). Peritubular/interstitial Mo did not associate with glomerulitis. Capillaritis did not show association with peritubular/interstitial or glomerular Mo. As regards graft survival, the infiltration of Mo in glomeruli interfered with allograft survival (p = 0.01). The group with a mean value of ≥4 glomerular Mo presented worse survival at the time of the 1-year follow-up. According to the literature, our data showed that infiltration of mononuclear cells was associated with C4d staining, microcirculation injury, and glomerulitis, in particular, and that glomerular macrophages could influence renal allograft survival.

Anemia at one year is an independent risk factor of graft survival.

BACKGROUND: Post-transplant anemia is multifactorial and highly prevalent. Some studies have associated anemia with mortality and graft failure. The purpose of this study was to assess whether the presence of anemia at 1 year is an independent risk factor of mortality and graft survival. METHODS: All patients transplanted at a single center who survived at least 1 year after transplantation and showed no graft loss (n = 214) were included. Demographic and clinical data were collected at baseline and at 1 year. Patients were divided into two groups (anemic and nonanemic) based on the presence of anemia (hemoglobin < 130 g/l in men and 120 g/l in women). RESULTS: Baseline characteristics such as age, gender, type of donor, CKD etiology, rejection, and mismatches were similar in both groups. Creatinine clearance was similar in both anemic and nonanemic groups (69.32 ± 29.8 × 75.69 ± 30.5 ml/mim; P = 0.17). A Kaplan-Meier plot showed significantly poorer death-censored graft survival in the anemic group, P = 0.003. Multivariate analysis revealed that anemic patients had a hazard ratio for the graft loss of 3.85 (95% CI: 1.49-9.96; P = 0.005). CONCLUSIONS: In this study, anemia at 1 year was independently associated with death-censored graft survival and anemic patients were 3.8-fold more likely to lose the graft.

Alteraçöes glomerulares primárias após transplante renal / Primary glomerular changes after kidney transplantation

As glomerulopatias primárias que se desenvolvem após o transplante renal foram revisadas. Glomerulopatia do transplante ocorre em 30 a 70 por cento e leva a perda do enxerto em 60 por cento dos casos. Glomerulonefrite recorrente ocorre em 5 por cento, perda do enxerto em 1 a 5 por cento e é mais prevalente na glomerulonefrite membranoproliferativa (Tipo I e II) e glomerulosclerose segmentar e focal. A última progride para insuficiência renal em 20 a 40 por cento dos pacientes, após 50 meses. A glomerulonefrite membranosa é o tipo histológico que mais frequentemente se desenvolve em pacientes que nunca apresentaram esta nefropatia antes do transplante, a assim chamada glomerulopatia "de novo", em cujo diagnóstico é fundamental o estudo anátomo-patológico completo do rim primitivo. Sua freqüência varia entre 10 a 40 por cento.