Effects of Plasma-Lyte® and 0. 9% saline in renal function after deceased-donor kidney transplant: a randomized controlled trial

Abstract Background The influence of different crystalloid solutions infused during deceased-donor kidney transplant on the incidence of delayed graft function remains unclear. We investigated the influence of Plasma-Lyte® vs. 0.9% saline on the incidence of delayed graft function in deceased-donor kidney transplant recipients. Methods We conducted a single-blind randomized controlled trial of 104 patients aged 18 to 65 years who underwent deceased-donor kidney transplant under general anesthesia. Patients were randomly assigned to receive either Plasma-Lyte® (n = 52) or 0.9% saline (n = 52), at the same infusion volume, for intraoperative fluid replacement. The primary outcome was the occurrence of delayed graft function. Secondary outcomes included metabolic and electrolytic changes at the end of surgery. Results Two patients in the Plasma-Lyte® group and one in the 0.9% saline group died postoperatively and were not included for analysis. The incidence of delayed graft function in Plasma-Lyte® and 0.9% saline groups were 60.0% (95% Confidence Interval [95% CI 46.2-72.4]) and 74.5% (95% CI 61.1-84.4), respectively (p= 0.140). Mean (standard deviation) values of immediate postoperative pH and serum chloride levels in Plasma-Lyte® and 0.9% saline groups were 7.306 (0.071) and 7.273 (0.061) (p= 0.013), and 99.6 (4.2) mEq.L-1 and 103.3 (5.6) mEq.L-1, respectively (p< 0.001). All other postoperative metabolic and electrolyte variables were not statistically different at the immediate postoperative period (p> 0.05). Conclusion In deceased-donor kidney transplant recipients, the incidence of delayed graft function is not influenced by Plasma-Lyte® or 0.9% saline used for intraoperative fluid replacement.

Comparative analysis of kidney transplant costs related to recovery of renal function after the procedure / Análise comparativa dos custos do transplante renal relacionados à recuperação da função renal após o procedimento

Abstract Introduction: The number of kidney transplants (KTx) is increasing in Brazil and, consequently, the costs of this procedure increase the country's health budget. We retrospectively evaluated the data of kidney transplant procedures until hospital discharge, according to kidney function recovery after the procedure. Methods: Retrospective analysis of the non-sensitized, 1st KTx from deceased donors performed between Jan/2010 to Dec/2017. Results: Out of the 1300 KTx from deceased donors performed in this period, 730 patients were studied and divided into 3 groups: Immediate Renal Function (IRF) - decrease in serum creatinine ≥ 10% on two consecutive days; Delayed Graft Function (DGF) - decrease in serum creatinine <10% on two consecutive days, without the need for dialysis, and Dialysis (D) - need for dialysis during the first week. Patients in group D stayed longer in the hospital compared to DGF and IRF (21, 11 and 8 days respectively, p < 0.001). More D patients (21%) were admitted to the ICU and performed a greater number of laboratory tests (p < 0.001) and renal biopsies (p < 0.001), in addition to receiving a higher amount of immunosuppressants. Total hospital costs were higher in group D and DGF compared to IRF (U$ 7.021,48; U$ 3.603,42 and U$ 2.642,37 respectively, p < 0.001). Conclusion: The costs of the transplant procedure is impacted by the recovery of kidney function after the transplant. The reimbursement for each of these different kidney function outcomes should be individualized in order to cover their real costs.

Resumo Introdução: O número de transplantes renais (KTx, do inglês kidney transplant) está aumentando no Brasil e, consequentemente, os custos deste procedimento aumentam o orçamento de saúde do país. Avaliamos retrospectivamente dados dos procedimentos de transplantes renais até a alta hospitalar, de acordo com a recuperação da função renal após o procedimento. Métodos: Análise retrospectiva dos 1º KTx de doadores falecidos, não sensibilizados, realizados entre Jan/2010 a Dez/2017. Resultados: Dos 1300 KTx de doadores falecidos realizados neste período, 730 pacientes foram estudados e divididos em 3 grupos: Função Renal Imediata (FRI) - diminuição na creatinina sérica ≥ 10% em dois dias consecutivos; Função Retardada do Enxerto (FRE) - diminuição na creatinina sérica <10% em dois dias consecutivos, sem necessidade de diálise, e Diálise (D) - necessidade de diálise durante a primeira semana. Pacientes no grupo D permaneceram mais tempo no hospital em comparação com FRE e FRI (21, 11 e 8 dias dias respectivamente, p < 0,001). Mais pacientes do grupo D (21%) foram admitidos na UTI e realizaram um maior número de testes laboratoriais (p < 0,001) e biópsias renais (p < 0,001), além de receberem uma quantidade maior de imunossupressores. Os custos hospitalares totais foram mais elevados nos grupos D e FRE em comparação com FRI (U$ 7.021,48; U$ 3.603,42 e U$ 2.642,37 respectivamente, p < 0,001). Conclusão: Os custos do procedimento de transplante são impactados pela recuperação da função renal após o transplante. O reembolso para cada um desses diferentes desfechos da função renal deve ser individualizado a fim de cobrir seus custos reais.

Predictive value of hypothermic machine perfusion parameters combined perfusate biomarkers in deceased donor kidney transplantation / 中华医学杂志(英文版)

BACKGROUND@#Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation.@*METHODS@#HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis.@*RESULTS@#In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806).@*CONCLUSION@#According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.

Características de los pacientes trasplantados renales con retraso de la función del injerto, asistidos en el servicio de terapia intensiva del Instituto de Cardiología de Corrientes entre 2016 y 2018 / Characteristics of renal transplant patients with delayed graft function, assisted in the intensive therapy service of the Institute of current Cardiology between 2016 and 2018

Esta investigación tuvo por objetivo describir las características de los pacientes trasplantados renales con retraso en la función del injerto. Estudio descriptivo, transversal y observacional. Población: trasplantados renales asistidos en el Instituto de Cardiología de Corrientes entre 2016 y 2018 que cumplieron los criterios de inclusión. Se utilizó formulario de elaboración propia; los datos se obtuvieron de revisión de historias clínicas. La información recolectada se analizó mediante programa informático Epidat_4.2. Se contó con el aval del comité de la institución. Se estudiaron 61 pacientes trasplantados; 43% pertenecía a donantes vivos y 57% a cadavéricos. El 66% de donantes cadavéricos tuvo retraso de la función del injerto, los de donantes vivos no lo presentaron. En cuanto al sexo 48% de los varones presentaron retraso en la función; en las mujeres fue el 28%. En edad de los pacientes, la media fue de 40,6 años ± 15,7; se observó mayor frecuencia de retrasos de la función en el grupo etario de 31 a 50 años con 44%. En cuanto al estado nutricional 17% que se encontraba con sobrepeso y 48% con bajo peso presentaron retraso de la función del injerto. Según los años en diálisis pre trasplante el 65% de aquellos con 4 a 7 años de diálisis presentaron retraso en la función del injerto. Según tiempo de isquemia fría del órgano trasplantado, 52% presentó retraso en la función del injerto cuando el tiempo fue mayor a 15 horas. En requerimiento de diálisis pos-operatorio, el 66% presentó retraso en la función del injerto y pertenecían a donantes cadavéricos. En índice de resistencia vascular renal en las primeras 24hs, el 65% con retraso de la función del injerto presentó índice patológico. En conclusión, sexo masculino, grupo etario de 31 a 50 años, tener alterado el estado nutricional, haberse dializado pre trasplante entre 4 a 7 años, padecer un tiempo prolongado de isquemia fría > 15 horas y presentar un índice de resistencia vascular renal patológico, son características presentes; en trasplantados renales con retraso en la función del injerto; y requieren ser tenidos en cuenta cuando se planean estas cirugías[AU]

Kidney transplantation with donors in severe acute kidney injury. Should we use these organs? Retrospective Case Series / Transplante renal com doadores em lesão renal aguda severa. Devemos utilizar esses órgãos? Série de casos retrospectiva

ABSTRACT Introduction: The number of incident and prevalent patients on dialysis has increased, as well as the number of candidates for renal transplantation in Brazil, without a proportional increase in the number of organ donors. The use of expanded kidneys, as to renal function, may be an alternative to increase the supply of organs. Objective: to discuss the feasibility of using expanded kidneys for renal function, which are in severe acute renal injury. Methods: All cases of renal transplantation of deceased donors performed at the Hospital das Clínicas de Botucatu of UNESP, from January 2010 to June 2018, totaling 732 cases were evaluated. Cases with final donor creatinine greater than 6 mg/dL were selected. Results: four patients were selected, of whom all donors were in severe acute kidney injury (AKI). These donors presented rhabdomyolysis as a probable cause of severe AKI, were young, with no comorbidities and had decreased urinary volume in the last 24 hours. The clinical evolution of all the recipients was satisfactory, with a glomerular filtration rate after transplantation ranging from 48 to 98 mL/min/1.73 m2. Conclusion: this series of cases shows the possibility of using renal donors in severe AKI, provided the following are respected: donor age, rhabdomyolysis as the cause of AKI, and implantation-favorable biopsy findings. Additional studies with better designs, larger numbers of patients and longer follow-up times are needed.

RESUMO Introdução: O número de pacientes incidentes e prevalentes em diálise tem aumentado, assim como o número de candidatos ao transplante renal no Brasil, sem um aumento proporcional do número de doadores de órgãos. O uso de rins expandidos, quanto à função renal, pode ser uma alternativa para aumentar a oferta de órgãos. Objetivo: discutir a viabilidade do uso de rins expandidos quanto à função renal, que estejam em lesão renal aguda severa. Métodos: foram avaliados todos os casos de transplante renal de doador falecido realizados no Hospital das Clínicas de Botucatu da UNESP, de janeiro de 2010 a junho de 2018, totalizando 732 casos. Selecionou-se os casos com creatinina final do doador maior do que 6 mg/dL. Resultados: quatro pacientes foram selecionados, dos quais todos os doadores estavam em lesão renal aguda (LRA) severa. Esses doadores apresentavam rabdomiólise como provável causa de LRA severa, eram jovens, sem comorbidades e apresentavam diminuição de volume urinário nas últimas 24 horas. A evolução clínica de todos os receptores foi satisfatória, com taxa de filtração glomerular após o transplante variando entre 48 a 98 mL/min/1,73m2. Conclusão: essa série de casos mostra a possibilidade de utilização de doadores renais em LRA severa, desde que respeitadas as condições seguintes: idade do doador, rabdomiólise como causa de LRA e achados de biópsia favoráveis à implantação. Estudos adicionais com melhores desenhos, maior número de pacientes e maiores tempos de seguimento são necessários.

Refractory ascites and graft dysfunction in early renal transplantation / Ascite refratária e disfunção do enxerto no pós-transplante renal precoce

Abstract The occurrence of ascites after Renal Transplant (RT) is infrequent, and may be a consequence of surgical or medical complications. Case report: 61 year-old, male, history of arterial hypertension, tongue carcinoma and alcoholic habits 12-20g/day. He had chronic kidney disease secondary to autosomal dominant polycystic kidney disease, without hepatic polycystic disease. He underwent cadaver donor RT in September 2017. He had delayed graft function by surgically corrected renal artery stenosis. He was admitted in January 2018 for ascites de novo, with no response to diuretics. HE had visible abdominal collateral circulation. Graft dysfunction, adequate tacrolinemia, Innocent urinary sediment, mild anemia, without thrombocytopenia. Serum albumin 4.0g / dL. Normal hepatic biochemistry. Peritoneal fluid with transudate characteristics and serum albumin gradient > 1.1. Ultrasound showed hepatomegaly, permeable vascular axes, without splenomegaly. Mycophenolate mofetil was suspended, with reduced remaining immunosuppression. He maintained refractory ascites: excluded infectious, metabolic, autoimmune and neoplastic etiologies. No nephrotic proteinuria and no heart failure. MRI: micronodules compatible with bile cysts. Upper Digestive Tract Endoscopy did not show gastroesophageal varicose veins. Normal abdominal lymphoscintigraphy. He underwent exploratory laparoscopy with liver biopsy: incomplete septal cirrhosis of probable vascular etiology some dilated bile ducts. He maintained progressive RT dysfunction and restarted hemodialysis. The proposed direct measurement of portal pressure was delayed by ascites resolution. There was further recovery of the graft function. Discussion: Incomplete septal cirrhosis is an uncommon cause of non-cirrhotic portal hypertension. Its definition is not well known, morphological and pathophysiological. We have not found published cases of post-RT ascites secondary to this pathology, described as possibly associated with drugs, immune alterations, infections, hypercoagulability and genetic predisposition.

Resumo A ocorrência de ascite no pós-Transplante Renal (TR) é infrequente, podendo ser consequência de complicações cirúrgicas ou médicas. Caso clínico: 61 anos, masculino, antecedentes de hipertensão arterial, carcinoma da língua e hábitos alcoólicos 12-20g/dia. Doença renal crônica secundária à doença renal poliquística autossômica dominante, sem poliquistose hepática. Submetido a TR de doador cadáver em setembro de 2017. Atraso na função de enxerto por estenose da artéria renal, corrigida cirurgicamente. Internado em janeiro de 2018 por ascite de novo, sem resposta a diuréticos. Circulação colateral abdominal visível. Disfunção do enxerto, tacrolinemia adequada. Sedimento urinário inocente. Anemia ligeira, sem trombocitopenia. Albumina sérica 4,0g/dL. Bioquímica hepática normal. Líquido peritoneal com características de transudado e gradiente sero-ascítico de albumina > 1,1. Ecografia com hepatomegalia, eixos vasculares permeáveis, sem esplenomegalia. Suspendeu micofenolato mofetil, reduziu restante imunossupressão. Manteve ascite refratária: excluídas etiologias infecciosas, metabólicas, autoimunes e neoplásicas. Sem proteinúria nefrótica e sem insuficiência cardíaca. RM: micronódulos compatíveis com quistos biliares. EDA sem varizes gastroesofágicas. Linfocintigrafia abdominal normal. Submetido a laparoscopia exploradora com biópsia hepática: cirrose septal incompleta de provável etiologia vascular, alguns ductos biliares dilatados. Manteve disfunção progressiva do TR, reiniciou hemodiálise. Proposta medição direta da pressão portal, protelada por resolução da ascite. Recuperação posterior da função de enxerto. Discussão: A cirrose septal incompleta é uma causa incomum de hipertensão portal não cirrótica. A sua definição é morfológica e a fisiopatologia, pouco conhecida. Não encontramos publicados casos de ascite pós-TR secundária a esta patologia, descrita como possivelmente associada a fármacos, alterações imunitárias, infecções, hipercoagulabilidade e predisposição genética.

Long-term effects of delayed graft function duration on function and survival of deceased donor kidney transplants / Efeitos de longo prazo da duração da função tardia do enxerto sobre a função e sobrevida de transplantes renais com doadores falecidos

Abstract Introduction: Delayed graft function (DGF) is a frequent complication after deceased donor kidney transplantation with an impact on the prognosis of the transplant. Despite this, long-term impact of DGF on graft function after deceased donor kidney transplantation has not been properly evaluated. Objective: The main objective of this study was to evaluate risk factors for DGF and the impact of its occurrence and length on graft survival and function. Methods: A retrospective cohort study was performed in 517 kidney transplant recipients who received a deceased donor organ between January 2008 and December 2013. Results: The incidence of DGF was 69.3% and it was independently associated with donor's final serum creatinine and age, cold ischemia time, use of antibody induction therapy and recipient's diabetes mellitus. The occurrence of DGF was also associated with a higher incidence of Banff ≥ 1A grade acute rejection (P = 0.017), lower graft function up to six years after transplantation and lower death-censored graft survival at 1 and 5 years (P < 0.05). DGF period longer than 14 days was associated with higher incidence of death-censored graft loss (P = 0.038) and poorer graft function (P < 0.001). No differences were found in patient survival. Conclusions: The occurrence of DGF has a long-lasting detrimental impact on graft function and survival and this impact is even more pronounced when DGF lasts longer than two weeks.

Resumo Introdução: A função tardia do enxerto (FTE) é uma complicação frequente após transplantes renais com doadores falecidos com repercussões sobre o prognóstico do transplante. Contudo, o impacto a longo prazo da FTE sobre a função do enxerto após transplante renal com doador falecido não foi avaliado adequadamente. Objetivo: O principal objetivo do presente estudo foi avaliar os fatores de risco para FTE e o impacto de sua ocorrência e duração na sobrevida e função do enxerto. Métodos: O presente estudo observacional retrospectivo incluiu 517 receptores de transplante renal que receberam órgãos de doadores falecidos entre janeiro de 2008 e dezembro de 2013. Resultados: A incidência de FTE foi de 69,3%. Foi identificada associação independente entre FTE e creatinina sérica final e idade do doador, tempo de isquemia fria, uso de terapia de indução com anticorpos e diabetes mellitus do receptor. A ocorrência de FTE também foi associada a incidência mais elevada de rejeição aguda com classificação de Banff ≥ 1 A (P = 0,017), função reduzida do enxerto até seis anos após o transplante e menor sobrevida do enxerto censurada para óbito em 1 e 5 anos (P <0,05). Períodos de FTE superiores a 14 dias foram associados a maior incidência de perda do enxerto censurada para óbito (P = 0,038) e pior função do enxerto (P <0,001). Não foram identificadas diferenças de sobrevida nos pacientes. Conclusões: A ocorrência de FTE traz prejuízos de longa duração à função e sobrevida do enxerto. Tal impacto é ainda mais pronunciado quando a FTE persiste por mais de duas semanas.

Micro RNA 146a-5p expression in Kidney transplant recipients with delayed graft function / Expressão do Micro RNA 146a-5p em pacientes transplantados renais com disfunção inicial do enxerto

ABSTRACT Introduction: The development of novel non-invasive biomarkers of kidney graft dysfunction, especially in the course of the delayed graft function period would be an important step forward in the clinical practice of kidney transplantation. Methods: We evaluated by RT-PCR the expression of miRNA-146 to -5p ribonucleic micro-acids (miRNAs) in the peripheral blood and renal tissue obtained from kidney transplant recipients who underwent a surveillance graft biopsy during the period of delayed graft function. Results: In biopsy samples, the expression of miR-146a-5p was significantly increased in the group of patients with delayed graft function (DGF) (n = 33) versus stables patients (STA) (n = 13) and patients with acute rejection (AR) (n = 9) (p = 0.008). In peripheral blood samples, a non-significant increase of miR-146a-5p expression was found in the DGF group versus STA and AR groups (p = 0.083). No significant correlation was found between levels of expression in biopsy and plasma. ROC curve analysis revealed an AUC of 0.75 (95% CI: 0.62-0.88) for the renal tissue expression and 0.67 (95% CI 0.52-0.81) for the peripheral blood expression. Conclusion: We conclude that miR-146a-5p expression has a distinct pattern in the renal tissue and perhaps in the peripheral blood in the setting of DGF. Further refinements and strategies for studies should be developed in the field of non-invasive molecular diagnosis of kidney graft dysfunction.

RESUMO Introdução: O desenvolvimento de novos biomarcadores não invasivos para disfunção do enxerto renal, especialmente no decurso da disfunção inicial do enxerto, seria de enorme valia para a prática clínica do transplante renal. Métodos: A técnica de RT-PCR foi utilizada para avaliar a expressão de microRNA 146a-5p no sangue periférico e no tecido renal de receptores de transplante submetidos a biópsia renal de controle no decurso de disfunção inicial do enxerto. Resultados: A expressão de miR-146a-5p estava significativamente aumentada nas amostras de biópsia do grupo de pacientes com disfunção inicial do enxerto (DIE) (n = 33) em relação aos pacientes estáveis (n = 13) e aos com rejeição aguda (RA) (n = 9) (p = 0,008). Foi detectado aumento não significativo da expressão de miR-146a-5p nas amostras de sangue periférico do grupo com DIE em comparação aos pacientes estáveis e com RA (p = 0,083). Não foi identificada correlação significativa entre os níveis de expressão no plasma e na biópsia. A análise da curva COR revelou uma ASC de 0,75 (IC 95%: 0,62-0,88) para a expressão no tecido renal e de 0,67 (IC 95% 0,52-0,81) no sangue periférico. Conclusão: A expressão de miR-146a-5p tem um padrão distinto no tecido renal e talvez no sangue periférico em cenários de DIE. Maiores refinamentos e estratégias adicionais de estudo devem ser desenvolvidos na área do diagnóstico molecular não invasivo da disfunção do enxerto renal.

The future is coming: promising perspectives regarding the use of machine learning in renal transplantation / O futuro está chegando: perspectivas promissoras sobre o uso de machine learning no transplante renal

Abstract Introduction: The prediction of post transplantation outcomes is clinically important and involves several problems. The current prediction models based on standard statistics are very complex, difficult to validate and do not provide accurate prediction. Machine learning, a statistical technique that allows the computer to make future predictions using previous experiences, is beginning to be used in order to solve these issues. In the field of kidney transplantation, computational forecasting use has been reported in prediction of chronic allograft rejection, delayed graft function, and graft survival. This paper describes machine learning principles and steps to make a prediction and performs a brief analysis of the most recent applications of its application in literature. Discussion: There is compelling evidence that machine learning approaches based on donor and recipient data are better in providing improved prognosis of graft outcomes than traditional analysis. The immediate expectations that emerge from this new prediction modelling technique are that it will generate better clinical decisions based on dynamic and local practice data and optimize organ allocation as well as post transplantation care management. Despite the promising results, there is no substantial number of studies yet to determine feasibility of its application in a clinical setting. Conclusion: The way we deal with storage data in electronic health records will radically change in the coming years and machine learning will be part of clinical daily routine, whether to predict clinical outcomes or suggest diagnosis based on institutional experience.

Resumo Introdução: A predição de resultados pós-transplante é clinicamente importante e envolve vários problemas. Os atuais modelos de previsão baseados em padrões estatísticos são muito complexos, difíceis de validar e não fornecem previsões precisas. Machine Learning, é uma técnica estatística que permite que o computador faça previsões futuras usando experiências anteriores, está começando a ser usada para resolver essas questões. No campo do transplante renal, o uso da previsão computacional foi relatado na predição de rejeição crônica de aloenxerto, função tardia do enxerto e sobrevida do enxerto. Este artigo descreve os princípios e etapas de machine learning para fazer uma previsão e realiza uma breve análise das aplicações mais recentes de seu uso na literatura. Discussão: Existem evidências convincentes de que as abordagens de machine learning baseadas nos dados do doador e do receptor são melhores para proporcionar melhor prognóstico dos resultados do enxerto do que a análise tradicional. As expectativas imediatas que emergem dessa nova técnica de modelagem de previsão são que ela gerará melhores decisões clínicas baseadas em dados de práticas dinâmicas e locais e aperfeiçoará a alocação de órgãos, bem como o gerenciamento de cuidados pós-transplante. Apesar dos resultados promissores, ainda não há um número substancial de estudos para determinar a viabilidade de sua aplicação em um cenário clínico. Conclusão: A forma como lidamos com dados de armazenamento em prontuários eletrônicos de saúde mudará radicalmente nos próximos anos e a machine learning fará parte da rotina clínica diária, seja para prever resultados clínicos ou sugerir um diagnóstico baseado na experiência institucional.

Predicting urine output after kidney transplantation: development and internal validation of a nomogram for clinical use

ABSTRACT Purpose: To analyze pre-transplantation and early postoperative factors affecting post-transplantation urine output and develop a predictive nomogram. Patients and Methods: Retrospective analysis of non-preemptive first transplanted adult patients between 2001-2016. The outcomes were hourly diuresis in mL/Kg in the 1st (UO1) and 8th (UO8) postoperative days (POD). Predictors for both UO1 and UO8 were cold ischemia time (CIT), patient and donor age and sex, HLA I and II compatibility, pre-transplantation duration of renal replacement therapy (RRT), cause of ESRD (ESRD) and immunosuppressive regimen. UO8 predictors also included UO1, 1st/0th POD plasma creatinine concentration ratio (Cr1/0), and occurrence of acute cellular rejection (AR). Multivariable linear regression was employed to produce nomograms for UO1 and UO8. Results: Four hundred and seventy-three patients were included, mostly deceased donor kidneys' recipients (361, 70.4%). CIT inversely correlated with UO1 and UO8 (Spearman's p=-0.43 and −0.37). CR1/0 inversely correlated with UO8 (p=-0.47). On multivariable analysis UO1 was mainly influenced by CIT, with additional influences of donor age and sex, HLA II matching and ESRD. UO1 was the strongest predictor of UO8, with significant influences of AR and ESRD. Conclusions: The predominant influence of CIT on UO1 rapidly wanes and is replaced by indicators of functional recovery (mainly UO1) and allograft's immunologic acceptance (AR absence). Mean absolute errors for nomograms were 0.08 mL/Kg h (UO1) and 0.05 mL/Kg h (UO8).

Máquina de perfusão versus armazenamento estático na preservação renal de doadores com morte encefálica: revisão sistemática e metanálise / Machine perfusion versus cold storage in renal preservation of deceased donors with brain death: systematic review and meta-analysis

RESUMO Com a utilização crescente da máquina de perfusão no transplante renal, tem sido constatado que a isquemia dinâmica correlaciona-se à melhora da preservação orgânica. Nesse contexto, realizamos uma revisão sistemática que procurou avaliar a eficácia do uso de máquina de perfusão portátil (LifePort Kidney Transporter Machine®), utilizada no Brasil, comparada ao armazenamento estático, no que tange à função retardada do transplante renal de doadores com morte encefálica. Foi efetuada pesquisa bibliográfica, nas bases LILACS, MEDLINE via PubMed, Scopus, Clarivate Analytics, Cochrane Library, Embase, SciELO, além de busca manual no Google acadêmico. A revisão sistemática, finalizada em abril 2017, foi constituída somente por ensaios clínicos randomizados. Para metanálise, foram avaliadas Razão de Risco e Razão de Chance. Foram identificados 86 documentos e selecionados, ao final, dois artigos com critérios de elegibilidade para metanálise, de grupos europeus e brasileiros. Nestes, 374 rins foram alocados para a máquina de perfusão, e igual número para o armazenamento estático. A função retardada do enxerto foi constatada em 84 e 110 pacientes, respectivamente. Na metanálise, foram obtidas uma Razão de Risco de 0,7568 (p=0,0151) e uma Razão de Chance de 0,6665 (p=0,0225), ambas com intervalo de confiança de 95%. A máquina de perfusão reduziu a incidência de função retardada do enxerto de doadores com morte encefálica.

ABSTRACT With the increasing use of machine perfusion in kidney transplantation, it has been observed that dynamic ischemia correlates with the improvement of organ preservation. In this context, we performed a systematic review that aimed to evaluate the efficacy of the portable machine perfusion (LifePort Kidney Transporter Machine®), used in Brazil, compared to cold storage, regarding the delayed graft function of deceased donors with brain death. Literature search was carried out in LILACS, MEDLINE via PubMed, Scopus, Clarivate Analytics, Cochrane Library, Embase, and SciELO, as well as in Google Scholar manually. The systematic review consisted only of randomized clinical trials. For meta-analysis, relative risk and odds ratio were evaluated. Eighty-six documents were identified and two papers from European and Brazilian groups were selected at the end, with eligibility criteria for meta-analysis. In these, 374 kidneys were assigned to machine perfusion and 374 kidneys were assigned to cold storage. Delayed graft function was observed in 84 and 110 patients, respectively. In meta-analysis, a risk ratio of 0.7568 (p=0.0151) and an odds ratio of 0.6665 (p=0.0225) were obtained, both with a 95% confidence interval. Machine perfusion reduced the incidence of delayed graft function of deceased donors with brain death.

Perioperative factors associated with delayed graft function in renal transplant patients / Fatores perioperatórios associados à função retardada do enxerto em pacientes transplantados renais

ABSTRACT Introduction: Successful renal transplant and consequent good graft function depend on a good surgical technique, an anesthetic that ensures the hemodynamic stability of the receiver, and appropriate conditions of graft and recipient. Several factors can interfere with the perfusion of the graft and compromise its viability. The objective of this study was to evaluate perioperative factors associated with delayed graft function (DGF) in renal transplantation patients. Methods: This is a historical cohort study of patients who underwent renal transplantation between 2011 and 2013. Three hundred and ten transplants were analyzed. DGF was defined as the need for dialysis during the first week post-transplant. Logistic regression with a stepwise technique was used to build statistical models. Results: Multivariate analysis revealed the following risk factor for DGF: combined anesthesia technique (OR = 3.81, 95%CI, 1.71 to 9.19), a fluid regimen < 50 mL·kg-1 (OR = 3.71, 95%CI, 1.68 to 8.61), dialysis for more than 60 months (OR = 4.77, 95%CI, 1.93 to 12.80), basiliximab (OR = 3.34, 95%CI, 1.14 to 10.48), cold ischemia time > 12 hour (OR = 5.26, 95%CI, 2.62 to 11.31), living donor (OR = 0.19, 95%CI, 0.02 to 0.65), and early diuresis (OR = 0.02, 95%CI, 0.008 to 0.059). The accuracy of this model was 92.6%, calculated using the area under the ROC curve. The incidence of DGF in the study population was 76.1%. Conclusions: Combined anesthesia technique, dialysis for more than 60 months, basiliximab, and cold ischemia time > 12 hours are risk factor for DGF, while liberal fluid regimens and kidneys from living donors are protective factors.

RESUMO Introdução: O sucesso do transplante renal e a boa função do enxerto dependem de uma boa técnica cirúrgica, anestesia que assegure a estabilidade hemodinâmica do receptor e condições adequadas de enxerto e receptor. Diversos fatores podem interferir na perfusão do enxerto e comprometer sua viabilidade. O objetivo deste estudo foi avaliar os fatores perioperatórios associados à função retardada do enxerto (FRE) em pacientes transplantados renais. Métodos: Estudo de coorte histórica em 310 pacientes submetidos a transplante entre 2011 e 2013. A FRE foi definida como a necessidade de diálise durante a primeira semana pós-transplante. Utilizou-se regressão logística e técnica Stepwise para construir modelos estatísticos. Resultados: A análise multivariada revelou fatores associados à FRE: técnica de anestesia combinada (OR = 3,81,95% CI, 1,71 a 9,19), regime de fluidos < 50 mL.kg-1 (OR = 3,71,95% CI, 1,68 a 8,61), diálise por mais de 60 meses (OR = 4,77,95% IC, 1,93 a 12,80), basiliximab (OR = 3,34,95% IC, 1,14 a 10,48), tempo de isquemia fria > 12 horas (OR = 5,26,95 % IC, 2,62 a 11,31), doador vivo (OR = 0,19,95% CI, 0,02 a 0,65) e diurese precoce (OR = 0,02,95% IC, 0,008 a 0,059). A precisão desse modelo é de 92,6%, calculada usando a área sob a curva ROC. A incidência de FRE na população estudada foi de 76,1%. Conclusões: Técnica combinada de anestesia, diálise por mais de 60 meses, basiliximab e tempo de isquemia fria> 12 horas são fatores de risco para FRE; regimes de fluidos liberais e rins de doadores vivos são protetores.

Perfusión hipotérmica de máquina versus preservación en frío estático en el trasplante de riñón / Hypothermic machine perfusion versus static cold preservation in kidney transplantation

INTRODUCCIÓN: La adecuada preservación del aloinjerto previo al trasplante renal es crucial para mantener buenos resultados luego del trasplante. En la actualidad existen dos métodos principales, la perfusión hipotérmica asistida por una máquina y la preservación en frío estático. El objetivo principal de este resumen es comparar ambos sistemas de preservación. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos 10 revisiones sistemáticas que en conjunto incluyeron 34 estudios primarios, de los cuales 13 corresponden a ensayos aleatorizados. Concluimos que la preservación mediante perfusión hipotérmica de máquina probablemente disminuye el riesgo de retraso en el funcionamiento del injerto y podría llevar a un leve aumento en la sobrevida del injerto. Sin embargo, no existen diferencias en la sobrevida del paciente entre ambos métodos.

INTRODUCTION: The adequate preservation of the allograft prior to kidney transplant is key for a good outcome after transplantation. Currently, there are two main methods: hypothermic machine perfusion and static cold preservation. The main objective of this summary is to compare both preservation systems. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified 10 systematic reviews including 34 primary studies, of which 13 were randomized trials. We concluded preservation by hypothermic machine perfusion probably decreases the risk of delayed graft function and could lead to a slight increase in graft survival. However, there are no differences in patient survival between the two methods.

Kidney transplantation using expanded criteria deceased donors with terminal acute kidney injury: a single center experience in Korea

PURPOSE: We investigated the clinical outcomes of deceased donor kidney transplantation (KT) using kidneys with terminal acute kidney injury (AKI). METHODS: Between February 2000 and December 2013, we performed 202 deceased donor renal transplants from 159 brain dead donors. According to the expanded criteria donor (ECD) and AKI network criteria, we divided 202 recipients into 4 groups: Group I: Non-AKI & standard criteria donor (SCD) (n = 97); group II: Non-AKI & ECD (n = 15); group III: AKI & SCD (n = 52); and group IV: AKI & ECD (n = 38). RESULTS: The incidence of delayed graft function (DFG) was significantly higher in patients with AKI than it was in the non-AKI group (P = 0.008). There were no significant differences among the 4 groups in graft survival (P = 0.074) or patient survival (P = 0.090). However, the long-term allograft survival rate was significantly lower in group IV than it was in other groups (P = 0.024). CONCLUSION: Allografts from deceased donors with terminal AKI had a higher incidence of DGF than did those from donors without AKI. However, there is no significant difference in graft and patient survival rates among the groups. So, the utilization of renal grafts from ECDs with terminal AKI is a feasible approach to address the critical organ shortage.

Predictive Score Model for Delayed Graft Function Based on Hypothermic Machine Perfusion Variables in Kidney Transplantation / 中华医学杂志(英文版)

Background@#Hypothermic machine perfusion (HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function (DGF) by HMP parameters is still controversial. Therefore, we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment.@*Methods@#From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios (ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model.@*Results@#HMP duration (OR = 1.165, 95% confidence interval [CI]: 1.008-1.360, P = 0.043), resistance (OR = 2.190, 95% CI: 1.032-10.20, P < 0.001), and flow rate (OR = 0.931, 95% CI: 0.894-0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories (scores 0-3, 4-7, 8-11, and 12-14) according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c-statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow (P = 0.012) and resistance (P = 0.006).@*Conclusion@#The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.

Beneficial Effect of Moderately Increasing Hypothermic Machine Perfusion Pressure on Donor after Cardiac Death Renal Transplantation / 中华医学杂志(英文版)

Background@#Vascular resistance and flow rate during hypothermic machine perfusion (HMP) of kidneys is correlated with graft function. We aimed to determine the effects of increasing HMP pressure versus maintaining the initial pressure on kidney transplantation outcomes.@*Methods@#We retrospectively reviewed the data of 76 primary transplantation patients who received HMP-preserved kidneys from 48 donors after cardiac death between September 1, 2013, and August 31, 2015. HMP pressure was increased from 30 to 40 mmHg (1 mmHg = 0.133 kPa) in kidneys with poor flow and/or vascular resistance (increased pressure [IP] group; 36 patients); otherwise, the initial pressure was maintained (constant pressure group; 40 patients). Finally, the clinical characteristics and transplantation outcomes in both groups were assessed.@*Results@#Delayed graft function (DGF) incidence, 1-year allograft, patient survival, kidney function recovery time, and serum creatinine level on day 30 were similar in both groups, with improved flow and resistance in the IP group. Among patients with DGF, kidney function recovery time and DGF duration were ameliorated in the IP group. Multivariate logistic regression analysis revealed that donor hypertension (odds ratio [OR]: 1.43, 95% confidence interval [CI]: 1.02-2.06, P = 0.035), donor terminal serum creatinine (OR: 1.27, 95% CI: 1.06-1.62, P = 0.023), warm ischemic time (OR: 3.45, 95% CI: 1.97-6.37, P = 0.002), and terminal resistance (OR: 3.12, 95% CI: 1.76-6.09, P = 0.012) were independent predictors of DGF. Cox proportional hazards analysis showed that terminal resistance (hazard ratio: 2.06, 95% CI: 1.32-5.16, P = 0.032) significantly affected graft survival.@*Conclusion@#Increased HMP pressure improves graft perfusion but does not affect DGF incidence or 1-year graft survival.

A Preliminary Study to Revise the Marginal Donor Criteria of KONOS in Deceased Donor Kidney Transplantation / 대한이식학회지

BACKGROUND: The Korean Network for Organ Sharing (KONOS), which was established in December 31st, 1999, is a nationwide system of deceased donor detection and distribution. From its inception, KONOS has defined marginal donors and used this definition for over 15 years. However, this definition should be reevaluated to determine if it requires revision. This study was conducted to confirm the feasibility of the main study for revision of the marginal donor definition in deceased donor kidney transplantation. METHODS: This study is a retrospective meta-analysis of 786 patients who had deceased donor kidney transplant from six centers. After the data validation process, multivariable analysis was conducted to evaluate whether the marginal donor criteria of KONOS or UNOS expected adequately in terms of graft survival and delayed graft function (DGF). RESULTS: Neither the KONOS or UNOS criteria affected graft survival. Expanded criteria for donors of UNOS was a risk factor for DGF. However, KONOS criteria did not affect DGF. CONCLUSIONS: Based on this preliminary study, there is a need to conduct a study to revise the marginal donor criteria of KONOS in deceased donor kidney transplantation. Such a study should have large scale and long-term follow-up data.

Immunologic Mechanism of Ischemia Reperfusion Injury in Transplantation / 대한이식학회지

Ischemia-reperfusion injury (IRI) is an inevitable consequence of organ transplantation that has major consequences for graft-and patient survival. During transplantation procedures, allografts are exposed to various periods of complete ischemia. Ischemic insult starts with brain death, and its associated hemodynamic disturbances continue during donor organ procurement, cold preservation, and implantation. Ischemia-reperfusion injury, which is a risk factor for acute graft injury, delayed graft function, and acute and chronic rejection, is triggered following reperfusion. Along the cascade of pathogenic events that accompany ischemic insults and cause IRI, there has been an appreciation for various immune mechanisms within the allograft itself. The pathophysiological events associated with IRI originate in signals derived from pattern recognition receptors (PRRs) expressed in the donor organ. Danger associated molecular patterns (DAMP) released from injured cells serve as ligands for PRRs expressed on many cells in the donor organ. Activation of PRR signaling in the donor organ leads to production of proinflammatory cytokines and activates the innate immune system, triggering adaptive immune responses as well as cell death signaling, ultimately worsening the initial ischemic injury. Accordingly, deciphering the inflammatory pathway of innate immunity in IRI may provide a good therapeutic target to block acute sterile inflammation caused by tissue damage.

Comparative study between kidney transplantation with deceased donor expanded criteria and donor standard criteria in a single center in Brazil / Estudo comparativo entre transplantes renais com doador falecido critério expandido e critério padrão em um único centro no Brasil

Abstract Introduction: Kidney transplants with expanded criteria donor have been associated with improved patient survival compared to those who remain on dialysis. Objective: To compare renal function and survival of the kidney graft of deceased donor with expanded criteria and standard criteria over a year in a single transplant center. Methods: 255 kidney transplant recipients with deceased donor were included in the study between the years 2011 to 2013 and they were separated into two groups according to the type of donor (expanded criteria donor - ECD - and standard criteria donor - SCD). Results: 231 deceased donor transplants (90.6%) were performed with standard criteria donor (SCD) and 24 (9.4%) with expanded criteria donor (ECD). There was no difference in the prevalence of delayed graft function - DGF - (62.9% vs. 70.8%; p = 0.44). Expanded criteria donor group had lower glomerular filtration rate (GFR) at the end of the 1st year (56.8 ± 26.9 vs. 76.9 ± 23.7; p = 0.001). Patient survival was significantly lower in the ECD group, but the graft survival was not different after death-censored analysis. Conclusion: The ECD group was associated with significantly lower levels of GFR during the first year of transplant and a lower patient survival at the 1st year when compared to the SCD.

Resumo Introdução: A aceitação dos rins com critério expandido de doação tem sido associada com melhor sobrevida do paciente em comparação àqueles que permanecem em terapia dialítica. Objetivo: Comparar a função renal e a sobrevida do enxerto renal de doador falecido critério expandido com os de doador falecido critério padrão ao longo de um ano em um único centro de transplantes. Métodos: Foram incluídos 255 receptores de transplante renal com doador falecido, realizados entre os anos de 2011 a 2013, sendo divididos em dois grupos segundo o tipo de doador (critério expandido - DCE - ou padrão -DCP). Resultados: Foram avaliados 231 receptores com doador critério ideal (90,6%) e 24 com doador critério expandido (9,4%). Não houve diferença na prevalência de função retardada do enxerto - DGF - (62,9% no DCP vs. 70,8% no DCE; p = 0,44) nos dois grupos. Os transplantes com DCE apresentaram uma taxa de filtração glomerular (TFG) significativamente inferior aos 12 meses (56,8 ± 26,9 vs. 76,9 ± 23,7; p = 0,001). A sobrevida dos pacientes em 1 ano foi significativamente inferior no grupo de DCE, mas não houve diferença na sobrevida dos enxertos após exclusão de perdas por óbito com rim funcionante. Conclusão: O grupo com DCE associou-se com níveis significativamente mais baixos de TFG ao longo do primeiro ano de transplante, bem como uma menor sobrevida dos pacientes em 1 ano, quando comparado ao grupo com doador padrão.