Longitudinal Pharmacokinetics of Everolimus When Combined With Low-level of Tacrolimus in Elderly Renal Transplant Recipients.

BACKGROUND: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. METHODS: We studied 12-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 ± 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 ± 4 days), PK2 (65 ± 7 days), PK3 (106 ± 17 days), and PK4 (206 ± 40 days). Patients received EVL (target trough level (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL). RESULTS: Mean TCL-Ctrough was 7.2 ± 3.8, 4.9 ± 2.2, 4.9 ± 2.2, and 4.5 ± 1.2 ng/mL at PK1, PK2, PK3, and PK4, respectively. There were no differences among timepoints for mean EVL daily dose (data shown as PK3) (3.5 ± 1.3 mg/d), Ctrough (4.7 ± 2.5 ng/mL), AUC0-12h (106 ± 51 ng/h per mL), Caverage (8.8 ± 4.2 ng/mL), Cmax (19.2 ± 9.7 ng/mL), apparent Half-life (11.7 ± 4.2 hours), estimated total body clearance (0.39 ± 0.27 L/h), or fluctuation (166 ± 65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-Ctrough showed a very high correlation (r = 0.849) with AUC0-12h. CONCLUSIONS: Our data indicate that elderly renal transplant recipients starting EVL 1 month after transplantation along with a steady-state TCL level, present stable EVL-PK parameters without significant changes in dose or exposure during the first 6 months after renal transplantation.

Longitudinal Pharmacokinetics of Tacrolimus in Elderly Compared With Younger Recipients in the First 6 Months After Renal Transplantation.

BACKGROUND: Elderly (Eld) (≥60 years) recipients are receiving renal transplants more frequently. The pharmacokinetics (PK) studies of immunosuppressive drugs in healthy volunteers, rarely, include old patients. METHODS: We studied 208 12-hour tacrolimus (TAC) PK (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, 720 min) in 44 Eld (65 ± 3 years) and compared the results with 31 younger controls (Ctrl) (35 ± 6 years) recipients, taking oral TAC/mycophenolate sodium (MPS)/prednisone, at 4 different timepoints: PK1 (8 ± 2 days; n = 72), PK2 (31 ± 4 days; n = 61), PK3 (63 ± 6 days; n = 44), and PK4 (185 ± 10 days; n = 31). Tacrolimus PK was measured by ultraperformance liquid chromatography coupled to a mass spectrometer repetition and noncompartmental PKs were analyzed using Phoenix WinNonlin. RESULTS: Mean TAC dose was lower in the Eld group than in Ctrl ones throughout timepoints either by total daily dose or adjusted (Adj) per body weight. Mean TAC trough level (Cmin), used to adjust daily dose, was not different between the 2 groups in all timepoints. AdjCmax and AdjTAC-area under the curve at dosing interval were both higher in the Eld compared to the Ctrl group in PKs1, 3, and 4. Estimated total body clearance normalized by dose and weight was lower in the Eld group compared with the Ctrl in all PKs and statistically lower at PKs 1 and 3. Similar to younger recipients TAC trough level has also a high correlation (R = 0.76) with area under the curve at dosing interval. CONCLUSIONS: These data indicate that Eld recipients have a lower TAC clearance and therefore need a lower TAC dose than younger recipients.

Evaluation of MDRD4, CKD-EPI, BIS-1, and modified Cockcroft-Gault equations to estimate glomerular filtration rate in the elderly renal-transplanted recipients.

Equations to estimate glomerular filtration rate (eGFR) were developed in patients using the variables age, body weight, and serum creatinine, which may be different in the elderly. Elderly renal transplant patients (EG; n=70; mean age 65 ± 4 y) who measured plasma 51 Cr-EDTA-Clearance (mGFR) had mGFR compared to eGFR obtained by the Cockcroft-Gault corrected by body surface area (CG-BSA), the modification of diet in renal disease (MDRD-4), the Berlin Initiative Study (BIS-1), and the chronic kidney disease epidemiology collaboration (CKD-EPI). Results were validated using a cohort of 43, of the 70 elderly recipients, who performed a second 51 Cr-EDTA-Clearance. Mean mGFR was 47 ± 16 mL/min/1.73 m2 and statistically lower than eGFR by MDRD (52 ± 19, P=.001) and BIS-1 (51 ± 13, P=.007) but not different from the CG-BSA (47 ± 15) and CKD-EPI (49 ± 18). The CKD-EPI and CG-BSA presented the lowest bias but only CKD-EPI also showed the highest 30% and 10% accuracy. The same findings were repeated in the validation set. For a cohort of elderly recipients ≥65 years (n=35, 68 ± 3y), the CKD-EPI performed better with the lowest bias (0 ± 12 mL/min/1.73 m2 ) and best 30% and 10% accuracy. The CKD-EPI equation is a valuable tool to monitor GFR in the elderly RTx recipients.

Transplantation with kidneys retrieved from deceased donors with acute renal failure.

BACKGROUND: The discard rate of kidneys recovered from deceased donors with acute renal failure (ARF) is higher compared with those without ARF mainly due to the uncertainty regarding short-term and long-term outcomes. METHODS: We retrospectively analyzed 1-year patient, graft, and rejection-free survivals and renal function of transplantations performed with kidneys recovered from deceased donors with or without ARF, defined as serum creatinine level of more than 1.5 mg/dL. We performed multivariable analysis to evaluate whether ARF was an independent risk factor associated with inferior outcomes. RESULTS: Of a total of 1518 patients, 253 received kidneys from expanded-criteria donors (ECD; with ARF [n=116] and without ARF [n=137]) and 1265 from standard-criteria donors (SCD; with ARF [n=369] and without ARF [n=896]). The incidence of delayed graft function was higher in ECD (68.1% vs. 58.4%; P=0.072) and SCD (69.9% vs. 50.6%; P<0.001) recipients of kidneys with ARF compared with those without ARF, respectively. At 1 year, patient, graft, and rejection-free survivals were not statistically different in SCD or ECD recipients with or without ARF. Renal function at 1 year was similar in recipients of ECD (41.9±26.3 vs. 40.1±21.7 mL/min; P=0.565) or SCD (50.9±29.9 vs. 53.6±28.5 mL/min; P=0.131) kidneys with and without ARF, respectively. Compared with kidneys without ARF, receiving a kidney allograft with ARF was not associated with increased risk of death, graft lost, or inferior renal function 1 year after transplantation. CONCLUSION: In this cohort of patients, kidneys from deceased donors with ARF provided graft survival and renal function comparable with kidneys from donors without ARF 1 year after transplantation.

O contexto do transplante de órgãos no Brasil em 2011 / The context of organ transplantation in Brazil in 2011

O Sistema Nacional de Transplantes (SNT) brasileiro coordena e regulamenta o maior programa de transplantes público do mundo. Com o seu estabelecimento, em 1997, o número de transplantes renais aumentou de 920 (5,8 por milhão de população - pmp), em 1998, para 4.957 (26 pmp) em 2011. Existem disparidades geográficas evidentes nos desempenhos entre as cinco regiões nacionais. Estas disparidades são diretamente relacionadas à densidade populacional regional, ao produto interno bruto e ao número de médicos com treinamento em transplante. Acompanhando o desafio de atenuar as disparidades regionais no acesso ao transplante, o sistema pode ser aperfeiçoado pela criação de um registro nacional para receptores de transplante e de doadores vivos de rim, e também pela promoção de estudos clínicos e experimentais voltados a melhor compreender a resposta imune relacionada ao transplante em nossa população.

The Brazilian National Tranplant System (SNT) coordinates and regulates perhaps the largest public transplant program worldwide. Since its establishment in 1997, the number of kidney transplants increased from 920 (5.8 pmp) in 1998 to 4,957 (26 pmp) in 2011. There are clear regional disparities in performance across all national regions. These disparities are directly related to regional population density, gross domestic product, and number of tranplant physicians. Besides the challenge of reducing the regional disparities related to the access to transplantation, it can be further improved by creating a national outcome registry for transplant recipient and for living kidney donors, and also by promoting clinical and experimental studies aimed to better understand the immune response related to transplantation in our population.

Kidney transplantation in Brazil and its geographic disparity.

The Brazilian National Transplantation System coordinates and regulates perhaps the largest public transplantation program worldwide. Since its implementation in 1997, the number of kidney transplantations increased from 920 (5.8 pmp) in 1998, to 4,630 (24.1 pmp) in 2010. This growth was primarily due to the increased number of effective donors (from 1.8 pmp in 1998 to 9.3 pmp in 2010), with a corresponding increased number of kidneys transplanted from deceased donors (3.8 pmp in 1999 versus 9.9 pmp in 2010).The number of kidney transplantations from living donors has not increased significantly, from 1,065 (6.7 pmp) in 1998 to 1,641 (8.6 pmp) in 2010, either as a consequence of the observed increase in the deceased donor program or perhaps because of strict government regulations allowing only transplantations from related donors. From 2000 to 2009, the mean age of living donors increased from 40 to 45 years, while it increased from 33 to 41 years for deceased donors, of whom roughly 50% die of stroke. There are clear regional disparities in transplantation performance across the national regions. While the state of São Paulo is ranked first in organ donation and recovery (22.5 pmp), some states of the Northern region have much poorer performances. These disparities are directly related to different regional population densities, gross domestic product distribution, and number of trained transplantation physicians. The initial evaluation of the centers with robust outcomes indicates no clear differences in graft survival in comparison with centers in the USA and Europe. Ethnicity and time on dialysis, but not the type of immunosuppressive regimen, decisively influence the measured outcomes. Since the implementation of national clinical research regulations in 1996, Brazilian centers have participated in a number of national and international collaborative trials for the development of immunosuppressive regimens. Besides the challenge of reducing the regional disparities related to access to transplantation, further improvements can be obtained by the creation of a national registry of the outcomes of transplanted patients and living donors, and also by the promotion of clinical and experimental studies to better understand the transplantation-related immune response of the Brazilian population.

O contexto do transplante renal no Brasil e sua disparidade geográfica / Kidney transplantation in Brazil and its geographic disparity

O Sistema Nacional de Transplantes (SNT) Brasileiro coordena e regulamenta o, provavelmente, maior programa de transplantes públicos do mundo. Desde o seu estabelecimento, em 1997, o número de transplantes renais aumentou de 920 (5,8 pmp), em 1988, para 4.630 (24,1 pmp), em 2010. Esse crescimento foi primariamente devido ao aumento no número de doadores efetivos (de 1,8 pmp em 1998 para 9,3 pmp em 2010), com aumento correspondente no número de rins transplantados de doadores falecidos (3,8 pmp em 1999 versus 9,9 pmp em 2010). O número de rins transplantados com órgãos de doadores vivos não aumentou significativamente, 1.065 (6,7 pmp), em 1998, para 1.641 (8,6 pmp), em 2010, tanto em consequência do melhor desempenho do programa de doadores falecidos, como talvez também devido a mais restrita regulamentação, permitindo apenas doação entre doadores vivos relacionados. De 2000 a 2009, a idade média dos doadores vivos aumentou de 40 para 45 anos, e a dos doadores falecidos, de 33 para 41 anos, com eventos cerebrovasculares sendo responsáveis por 50 por cento dos episódios de óbito atualmente. Existem disparidades geográficas evidentes nos desempenhos entre as 5 regiões nacionais. Enquanto o estado de São Paulo ocupa a primeira posição em doação e captação de órgãos (22,5 pmp), alguns estados da região Norte apresentam pequena ou nenhuma atividade de transplante. Essas disparidades estão diretamente relacionadas à densidade populacional regional, ao produto interno bruto e ao número de médicos com treinamento em transplante. A avaliação inicial de desfechos clínicos robustos não indica diferenças nas sobrevidas do enxerto em comparação com as observadas nos EUA e na Europa. A etnia e o tempo em diálise, mas não o tipo de imunossupressão, apresentam influência decisiva nos desfechos medidos. A regulamentação nacional da pesquisa clínica foi implementada a partir de 1996, permitindo a participação de centros brasileiros em numerosos estudos clínicos nacionais e internacionais para o desenvolvimento de regimes imunossupressores. Acompanhando o desafio de atenuar as disparidades regionais no acesso ao transplante, o sistema pode ser aperfeiçoado pela criação de um registro nacional para receptores de transplante e de doadores vivos de rins e também pela promoção de estudos clínicos e experimentais voltados a melhor compreender a resposta imune relacionada ao transplante em nossa população.

The Brazilian National Transplantation System coordinates and regulates perhaps the largest public transplantation program worldwide. Since its implementation in 1997, the number of kidney transplantations increased from 920 (5.8 pmp) in 1998, to 4,630 (24.1 pmp) in 2010. This growth was primarily due to the increased number of effective donors (from 1.8 pmp in 1998 to 9.3 pmp in 2010), with a corresponding increased number of kidneys transplanted from deceased donors (3.8 pmp in 1999 versus 9.9 pmp in 2010).The number of kidney transplantations from living donors has not increased significantly, from 1,065 (6.7 pmp) in 1998 to 1,641 (8.6 pmp) in 2010, either as a consequence of the observed increase in the deceased donor program or perhaps because of strict government regulations allowing only transplantations from related donors. From 2000 to 2009, the mean age of living donors increased from 40 to 45 years, while it increased from 33 to 41 years for deceased donors, of whom roughly 50 percent die of stroke. There are clear regional disparities in transplantation performance across the national regions. While the state of São Paulo is ranked first in organ donation and recovery (22.5 pmp), some states of the Northern region have much poorer performances. These disparities are directly related to different regional population densities, gross domestic product distribution, and number of trained transplantation physicians. The initial evaluation of the centers with robust outcomes indicates no clear differences in graft survival in comparison with centers in the USA and Europe. Ethnicity and time on dialysis, but not the type of immunosuppressive regimen, decisively influence the measured outcomes. Since the implementation of national clinical research regulations in 1996, Brazilian centers have participated in a number of national and international collaborative trials for the development of immunosuppressive regimens. Besides the challenge of reducing the regional disparities related to access to transplantation, further improvements can be obtained by the creation of a national registry of the outcomes of transplanted patients and living donors, and also by the promotion of clinical and experimental studies to better understand the transplantation-related immune response of the Brazilian population.

Steroid or tacrolimus withdrawal in renal transplant recipients using sirolimus.

BACKGROUND: Calcineurin inhibitor (CNI) and steroid (ST) withdrawal are strategies under investigation to reduce long-term toxicities associated with current immunosuppressive regimens. We conducted a single center, prospective trial comparing the efficacy and safety of CNI or ST withdrawal in kidney transplant recipients receiving sirolimus-based immunosuppressive regimen. METHODS: Forty-seven recipients of first renal transplant with non-HLA-identical living donors received sirolimus (SRL), tacrolimus (TAC), and ST without induction therapy and were randomized to undergo ST (TAC/SRL group, n = 24) or TAC (SRL/ST group, n = 21) withdrawal 3 months after transplantation. Primary efficacy and safety endpoints were the incidence of biopsy-confirmed acute rejection (BCAR) and renal function at 12 months. RESULTS: No differences were observed in the incidence of BCAR (4.2% vs. 9.5%), graft (95.8% vs. 95.6%), and patient (95.8% vs. 95.6%) survivals or in renal function (60 ± 11.5 vs. 63.4 ± 10.5 ml/min, P = 0.361). Higher mean cholesterol concentration was observed in the SRL/ST group (191.9 ± 63.3 vs. 241.6 ± 61.5 mg/dl, P = 0.019). Treatment discontinuation due to adverse events occurred in 12.5% of patients in TAC/SRL group and 21.7% in SRL/ST group. CONCLUSION: Within this short period of observation, our study was unable to detect any significant difference in major transplant outcomes comparing CNI and ST elimination strategies.

Clinical manifestations and evolution of infection by influenza A (H1N1) in kidney transplant recipients.

INTRODUCTION: The emergence of the pandemic outbreak of influenza A (H1N1) in April, 2009, represented a logistic challenge for public health. Although most infected patients presented clinical and evolutionary manifestations which were very similar to seasonal influenza, a significant number of individuals developed pneumonia and severe acute respiratory failure. The impact of influenza A (H1N1) in immunocompromised patients is not well established yet. METHODS: This study aimed to analyze the clinical presentations and evolution of influenza A (H1N1) in 19 kidney transplant recipients. Influenza A (H1N1) infection was confirmed by RT-PCR in all patients. Treatment included antiviral therapy with oseltamivir phosphate and antibiotics. RESULTS: The studied population was compounded mostly of white people (63%), males (79%), at a mean age of 38.6 ± 17 years and patients with at least one comorbidity (53%). Influenza A (H1N1) infection was identified 41.6 ± 49.6 months after transplantation. Common symptoms included cough (100%), fever (84%), dyspnea (79%), and myalgia (42%). Acute allograft dysfunction was observed in 42% of the patients. Five patients (26%) were admitted to the Intensive Care Unit, two (10%) required invasive ventilation support, and two (10%) required vasoactive drugs. Mortality rate was 10%. CONCLUSIONS: Acute renal allograft dysfunction was a common finding. Clinical, laboratory, and evolutionary characteristics were comparable to those in the general population.

Impact of delayed pancreatic graft function in simultaneous pancreas-kidney transplantation.

OBJECTIVE: Simultaneous pancreas-kidney transplantation is an effective treatment for patients with type 1 diabetes mellitus and end-stage chronic kidney disease. Delayed pancreatic graft function is a common and multifactor condition with significant impact in short-term outcome of simultaneous pancreas-kidney transplantations. The aim of this study was to analyze the impact of pancreatic delayed pancreatic graft function on simultaneous pancreas-kidney transplantation. METHODS: Donor and recipient's demographic data, percentage of panel reactivity, acute rejection incidence, and patient and grafts survivals were retrospectively analyzed in 180 SPKT performed between 2002 and 2007. RESULTS: The incidence of pancreatic delayed pancreatic graft function was 11%. Donors older than 45 years had significant risk of pancreatic delayed pancreatic graft function (OR 2.26; p < 0,05). Patients with pancreatic delayed pancreatic graft function had higher rates of acute renal rejection (47 versus 24%; p < 0.05), altered fasting plasma glucose (25 versus 5%; p < 0.05) and mean glycated hemoglobin (5.8 versus 5.4%; p < 0.05), than patients without pancreatic delayed pancreatic graft function at the end of the first year of follow up. There were no significant differences between patients with and without pancreatic delayed pancreatic graft function regarding patient survival (95 versus 88.7%; p = 0.38), pancreatic graft survival (90 versus 85.6%; p = 0.59) and renal graft survival (90 versus 87.2%; p = 0.70), respectively at the sample period of time. CONCLUSION: Pancreatic delayed pancreatic graft function had no significant impact in the short-term outcome of simultaneous pancreas-kidney transplantations. Although delayed pancreatic graft function had no impact on 1-year pancreas graft survival, it contributed to early pancreas graft dysfunction, as assessed by enhanced insulin and oral anti-diabetic drugs requirements.

Manifestações clínicas e evolução da infecção pelo vírus da influenza A (H1N1) em receptores de transplante renal / Clinical manifestations and evolution of infection by influenza A (H1N1) in kidney transplant recipients

INTRODUÇÃO: A emergência do surto pandêmico de influenza A, subtipo H1N1, em abril de 2009, representou um grande desafio para a logística de saúde pública. Embora a maioria dos pacientes infectados apresente manifestações clínicas e evolutivas muito semelhantes às observadas na influenza sazonal, um número significativo de indivíduos evolui com pneumonia e insuficiência respiratória aguda severa. O impacto da infecção pelo vírus influenza A, subtipo H1N1, em pacientes imunossuprimidos não é determinado. MÉTODOS: Neste estudo, foram analisadas a apresentação clínica e a evolução da influenza A, subtipo H1N1, em 19 receptores de transplante renal. Os pacientes receberam confirmação diagnóstica pela técnica de RT-PCR. O manejo clínico incluiu terapêutica antiviral com fosfato de oseltamivir e antibióticos. RESULTADOS: A população estudada foi predominantemente de indivíduos do sexo masculino (79 por cento), brancos (63 por cento), com idade média de 38,6 ± 17 anos e portadores de pelo menos uma comorbidade (53 por cento). A infecção por influenza A, subtipo H1N1, foi diagnosticada em média 41,6 ± 49,6 meses após o transplante. Os sintomas mais comuns foram: tosse (100 por cento), febre (84 por cento), dispneia (79 por cento) e mialgia (42 por cento). Disfunção aguda do enxerto foi observada em 42 por cento dos pacientes. Cinco pacientes (26 por cento) foram admitidos em Unidade de Terapia Intensiva, dois (10 por cento) necessitaram de suporte com ventilação invasiva e dois (10 por cento) receberam drogas vasoativas. A mortalidade foi de 10 por cento. CONCLUSÕES: A disfunção aguda do enxerto renal foi um achado frequente, e as características clínicas, laboratoriais e evolutivas foram comparáveis às da população geral.

INTRODUCTION: The emergence of the pan>demic outbreak of influenza A (H1N1) in April, 2009, represented a logistic challenge for public health. Although most infected patients presented clinical and evolutionary manifestations which were very similar to seasonal influenza, a significant number of individuals developed pneumonia and severe acute respiratory failure. The impact of influenza A (H1N1) in immunocompromised patients is not well established yet. METHODS: This study aimed to analyze the clinical presentations and evolution of influenza A (H1N1) in 19 kidney transplant recipients. Influenza A (H1N1) infection was confirmed by RT-PCR in all patients. Treatment included antiviral therapy with oseltamivir phosphate and antibiotics. RESULTS: The studied population was compounded mostly of white people (63 percent), males (79 percent), at a mean age of 38.6 ± 17 years and patients with at least one comorbidity (53 percent). Influenza A (H1N1) infection was identified 41.6 ± 49.6 months after transplantation. Common symptoms included cough (100 percent), fever (84 percent), dyspnea (79 percent), and myalgia (42 percent). Acute allograft dysfunction was observed in 42 percent of the patients. Five patients (26 percent) were admitted to the Intensive Care Unit, two (10 percent) required invasive ventilation support, and two (10 percent) required vasoactive drugs. Mortality rate was 10 percent. CONCLUSIONS: Acute renal allograft dysfunction was a common finding. Clinical, laboratory, and evolutionary characteristics were comparable to those in the general population.

Impacto da função retardada do enxerto pancreático no transplante simultâneo pâncreas-rim / Impact of delayed pancreatic graft function in simultaneous pancreas-kidney transplantation

OBJETIVO: O transplante pâncreas-rim é efetivo para pacientes com doença renal crônica terminal e diabetes mellitus insulino-dependente. A função retardada do enxerto pancreático é condição frequente exercendo impacto significativo nos resultados em curto prazo dos transplantes pâncreas-rim. O objetivo foi analisar o impacto da função retardada do enxerto pancreático no transplante pâncreas-rim. MÉTODOS: Análise retrospectiva de 180 receptores de transplante pâncreas-rim, incluindo dados demográficos dos doadores e dos receptores, a reatividade contra painel, a incidência de rejeição aguda e as sobrevidas do paciente e dos enxertos pancreático e renal. RESULTADOS: A incidência de função retardada do enxerto pancreático foi 11 por cento. A idade do receptor superior a 45 anos apresentou associação com o risco de desenvolvimento de função retardada do enxerto pancreático (Razão de chances 2,26; p < 0,05). Os pacientes com função retardada do enxerto pancreático apresentaram maior incidência de rejeição aguda renal (47 versus 24 por cento; p < 0,05), glicemia de jejum alterada (25 versus 5 por cento; p < 0,05) e média de hemoglobina glicada (5,8 versus 5,4 por cento; p < 0,05) ao final do primeiro ano de acompanhamento em relação aos pacientes sem função retardada do enxerto pancreático. Não houve diferenças estatisticamente significativas entre os grupos de pacientes com e sem função retardada do enxerto pancreático quanto à sobrevida do paciente (95 versus 88,7 por cento; p = 0,38), do enxerto pancreático (90 versus 85,6 por cento; p = 0,59) e do enxerto renal (90 versus 87,2 por cento; p = 0,70), respectivamente, nesse mesmo período. CONCLUSÃO: A função retardada do enxerto pancreático não exerceu impacto significativo nos resultados em curto prazo dos transplantes pâncreas-rim desta casuística...

OBJECTIVE: Simultaneous pancreas-kidney transplantation is an effective treatment for patients with type 1 diabetes melli>tus and end-stage chronic kidney disease. Delayed pancreatic graft function is a common and multifactor condition with significant impact in short-term outcome of simultaneous pancreas-kidney transplantations. The aim of this study was to analyze the impact of pancreatic delayed pancreatic graft function on simultaneous pancreas-kidney transplantation. METHODS: Donor and recipient's demographic data, percentage of panel reactivity, acute rejection incidence, and patient and grafts survivals were retrospectively analyzed in 180 SPKT performed between 2002 and 2007. RESULTS: The incidence of pancreatic delayed pancreatic graft function was 11 percent. Donors older than 45 years had significant risk of pancreatic delayed pancreatic graft function (OR 2.26; p < 0,05). Patients with pancreatic delayed pancreatic graft function had higher rates of acute renal rejection (47 versus 24 percent; p < 0.05), altered fasting plasma glucose (25 versus 5 percent; p < 0.05) and mean glycated hemoglobin (5.8 versus 5.4 percent; p < 0.05), than patients without pancreatic delayed pancreatic graft function at the end of the first year of follow up. There were no significant differences between patients with and without pancreatic delayed pancreatic graft function regarding patient survival (95 versus 88.7 percent; p = 0.38), pancreatic graft survival (90 versus 85.6 percent; p = 0.59) and renal graft survival (90 versus 87.2 percent; p = 0.70), respectively at the sample period of time. CONCLUSION: Pancreatic delayed pancreatic graft function had no significant impact in the short-term outcome of simultaneous pancreas-kidney transplantations. Although delayed pancreatic graft function had no impact on 1-year pancreas graft survival, it contributed to early pancreas graft dysfunction, as assessed by enhanced insulin and oral anti-diabetic drugs requirements.

Buttonhole, em casa de botão ou botoeira: uma técnica antiga redescoberta: [carta ao editor] / Buttonhole: an old technique rediscovered: [letter to the editor]

A presente carta ao Editor aborda os artigos de Silva et al. Õ e de Castro et al. ² que nos levam a dois tipos de comentários: o primeiro de ordem linguística, e o segundo referente a aspectos médicos.

The present letter to the Editor regards the articles by de Silva et al. Õ and de Castro et al. ² that lead us to two kinds of comments, the first refers to the language, and the second comment refers to the medical aspects.

One unit's experiences when establishing buttonhole technique, analysis of reasons for failure of procedure: a report.

The buttonhole technique of access of needle insertion into a single selected site in the arteriovenous fistula has proved to be a reliable alternative to older methods due to its overall low complication rates. Although the use of blunt needles improves the technique, the success rate of cannulation with these needles is difficult to predict. We analysed the short-term outcome of 16 patients receiving in-centre haemodialysis and compared clinical relevant parameters between patients with and without buttonhole technique failure. Our dialysis unit treats about 180 patients and is located in a tertiary hospital in Sao Paulo, Brazil. The variables as discussed in the paper were the same for both groups. The incidence of technique failure was 43.7%. Patients enrolled later in the study had a better buttonhole failure-free survival rates than patients enrolled at the beginning (p < 0.05). Patients' clinical characteristics did not predict the success rate of buttonhole tunnel tracks cannulation with blunt needles. This paper also reports on our successes and failures in buttonhole technique and gives some reasons and reflections for both.

Transpondo limites com doadores falecidos: transplantes bem-sucedidos com rins de doador com creatinina sérica igual a 13,1 mg/dL / Overcoming limits with deceased donors: successful renal transplantations from a donor with serum creatinine of 13.1 mg/dL

Doadores falecidos não limítrofes com insuficiência renal aguda podem ser uma opção segura para aumentar a oferta de rins para transplante. a avaliação histológica é fundamental para o estabelecimento do prognóstico funcional desses enxertos. Dois transplantes renais foram realizados com rins provenientes de um doador falecido jovem com insuficiência renal aguda severa sem comprometimento estrutural do parêquima renal. Ambos os enxertos apresentaram atraso de funcionamento no período pós-operatório, embora um deles com boa diurese inicial não tenha necessitado diálise. Função renal adequada foi observada a partir do 30º dia após o transplante. A insuficiência renal aguda severa no doador falecido não é fator de risco independente para a evolução em curto prazo do enxerto renal e não deve ser considerada contra-indicação absoluta para a realização do transplante.

Deceased donors not bordering with acute renal failure can be a safe option to increase the supply of kidneys for transplantation. histological evaluation is essential to establish the functional prognosis of these grafts. Two kidney transplants were performed with kidneys from a deceased donor couple with acute renal failure without severe structural impairment of parenchymal kidney. Both grafts were functioning in the late postoperative period, although one with good initial diuresis has not required dialysis. Adequate renal function was observed from day 30 after transplantation. Acute renal failure in severe deceased donor is not an independent risk factor for the development in short-term renal graft and should not be considered an absolute contraindication for transplantation was performed.

Incidência e fatores de risco para complicações infecciosas no primeiro ano após o transplante renal / Incidence of infectious complications and their risk factors in the first year after renal transplantation

Introdução: Complicações infecciosas determinam significativas morbidade e mortalidade após transplante renal. A imunossupressão utilizada representa o principal fator de risco e apresenta relação direta com a incidência e a severidade dos eventos infecciosos. Métodos: estudo de coorte, retrospectivo, que analisou a incidência e fatores de risco para ocorrência de infecções em 1.676 receptores de transplante renal durante o primeiro ano de acompanhamento. Resultados: Eventos infecciosos foram observados em 821 (49%) pacientes. O número médio de episódios infecciosos entre pacientes com pelo menos um episódio foi de 2,3 (1 - 12). As complicações infecciosas mais prevalentes foram infecção do trato urinário (31,3%), infecções por citomegalovírus (12%), infecção da incisão cirúrgica (10,3%), infecção por herpes vírus (9,1%), infecção pulmonar (5,2%) e infecção da corrente sanguínea (4,3%). O tempo de isquemia fria e a utilização de rins de doadores falecidos foram fatores de risco importantes para ocorrência de episódios infecciosos. Conclusões: Infecções apresentam prevalência elevada no primeiro ano de acompanhamento após o transplante. A principal complicação infecciosa foi a infecção do trato urinário.

Introduction: Infectious complications determine significant morbidity and mortality after renal transplantation. Immunosuppression used represents the main risk factor and has direct relation with the incidence and severity of infectious events. Methods: A cohort study, retrospective study examined the incidence and risk factors for occurrence of infections in 1676 renal transplant recipients during the first year of monitoring. Results: infectious events were observed in 821 (49%) patients. The average number of infectious episodes among patients with at least one episode was 2.3 (1-12). Infectious complications were most prevalent urinary tract infection (31.3%), cytomegalovirus infections (12%), infection of the surgical incision (10.3%), herpes virus infection (9.1%), pulmonary infection ( 5.2%) and bloodstream infection (4.3%). The cold ischemia time and the use of kidneys from deceased donors were significant risk factors for the occurrence of infectious episodes. Conclusions: Infections have a high prevalence in the first year of monitoring after transplantation. The main infectious complication was urinary tract infection.

Terapia de indução com alentuzumabe em receptores de transplante renal / Alemtuzumab induction in kidney transplant recipients

Introdução: Terapias de indução são usualmente utilizadas em receptores sensibilizados contra antígenos HLA, retransplantes e pacientes com risco de apresentar função tardia do enxerto (FTE). Método: Estudo retrospectivo com objetivo de avaliar os desfechos do transplante renal com doador falecido em pacientes que receberam indução com alentuzumabe (n=9). os pacientes do grupo controle, pareados conforme idade do receptor, tempo em diálise e tempo de isquemia fria, receberam timoglubina (n= 18). Resultados: Não houve diferença nas características demográficas entre os grupos. A idade média dos receptores foi de 47 anos e dos doadores, de 59 anos. Entre os doadores, 67 % apresentavam critério expandido. A incidência de FTE foi de 55% e 56%, respectivamente. Ao final do primeiro ano, não houve diferença nas sobrevidas livre de rejeição aguda comprovada por biópsia (67,0% e 84,6%, p=0,26), do paciente (83,3% e 81,2%; p=0,63), do enxerto (62,5% e 66,7%; p=0,82), do enxerto com óbito censorado (62,5% e 76,6%; p= 0,73) e na função renal 9depuração de creatinina: 61,6 +- 18,2 versus 52,7 +- 26,1 mL/min, p= 0,503). Houve maior redução na contagem de linfócitos no sangue periférico no grupo alentuzumabe (dia 14:172 +- 129 versus 390 +- 195 N/mm³, p< 0,05; dia 30: 135 +- 78 versus 263 +- 112 N/mm³, p< 0,05), porém com retorno mais rápido a valores normais após o transplante (dia 90: 683 +- 367 versus 282 +- 72 N/mm³, p < 0,05; dia 360: 1269 +- 806 versus 690 +- 444 N/mm³, p < 0,05). O custo do tratamento com alentuzumade foi de R$ 1.388,00, enquanto que o custo médio com timoglobulina foi de R$ 7.398,00. Conclusão: Essa experiência com alentuzumabe não demonstrou eficácia e/ou segurança superiores aos regimes com timoglobulina, apesar do custo ser em média cinco vezes menor.

Introduction: Induction Therapies are usually used in recipients sensitized against HLA antigens, retransplantation and patients at risk for delayed graft function (FTE). Method: A retrospective study to evaluate the outcomes of cadaveric renal transplant in patients who received induction alentuzumabe (n = 9). patients in the control group, matched by recipient age, time on dialysis and cold ischemia time, received timoglubina (n = 18). Results: No differences in demographic characteristics between groups. The average age of recipients was 47 years and from donors in 59 years. Among donors, 67% had expanded criteria. The incidence of FTE was 55% and 56% respectively. At the end of the first year, there was no difference in survival free of acute rejection proven by biopsy (67.0% and 84.6%, p = 0.26), the patient (83.3% and 81.2%, p = 0.63), graft (62.5% and 66.7%, p = 0.82) and death censored graft (62.5% and 76.6%, p = 0.73) and 9depuração renal creatinine: 61.6 + - 18.2 vs. 52.7 + - 26.1 mL / min, p = 0.503). Higher reduction in lymphocyte count in peripheral blood in group alentuzumabe (day 14:172 + - 129 versus 390 + - 195 N / mm ³, p <0.05; 30 days: 135 + - 78 versus 263 + - 112 N / mm ³, p <0.05), but with a faster return to normal after transplantation (day 90: 683 + - 367 versus 282 + - 72 N / mm ³, p <0.05, day 360: 1269 + - 806 versus 690 + - 444 N / mm ³, p <0.05). The cost of treatment with alentuzumade was R $ 1,388.00, while the average cost timoglobulina was R $ 7,398.00. Conclusion: This experience with alentuzumabe not demonstrated efficacy and / or security schemes with higher timoglobulina, despite the cost be on average five times lower.