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Made available in DSpace on 2022-04-28T19:44:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-02-01 This analysis, using data from the Brazilian kidney transplant (KT) COVID-19 study, seeks to develop a prediction score to assist in COVID-19 risk stratification in KT recipients. In this study, 1379 patients (35 sites) were enrolled, and a machine learning approach was used to fit models in a derivation cohort. A reduced Elastic Net model was selected, and the accuracy to predict the 28-day fatality after the COVID-19 diagnosis, assessed by the area under the ROC curve (AUC-ROC), was confirmed in a validation cohort. The better calibration values were used to build the applicable ImAgeS score. The 28-day fatality rate was 17% (n = 235), which was associated with increasing age, hypertension and cardiovascular disease, higher body mass index, dyspnea, and use of mycophenolate acid or azathioprine. Higher kidney graft function, longer time of symptoms until COVID-19 diagnosis, presence of anosmia or coryza, and use of mTOR inhibitor were associated with reduced risk of death. The coefficients of the best model were used to build the predictive score, which achieved an AUC-ROC of 0.767 (95% CI 0.698–0.834) in the validation cohort. In conclusion, the easily applicable predictive model could assist health care practitioners in identifying non-hospitalized kidney transplant patients that may require more intensive monitoring. Trial registration: ClinicalTrials.gov NCT04494776. Department of Internal Medicine Universidade Estadual Paulista-UNESP Department of Clinical Medicine Federal University of Ceará Hospital Universitário Walter Cantídio Hospital Geral de Fortaleza Department of Medicine Nephrology Division Federal University of São Paulo Department of Transplantation Hospital do Rim Fundação Oswaldo Ramos Renal Transplant Unit Hospital Israelita Albert Einstein Santa Casa de Misericórdia de Porto Alegre Hospital de Base Medical School FAMERP Federal University of Maranhão Hospital de Clínicas de Porto Alegre Federal Univertisy of Rio Grande do Sul Division of Nephrology and Kidney Transplantation Onofre Lopes University Hospital Hospital Santa Isabel Division of Nephrology School of Medical Sciences Renal Transplant Unit Renal Transplant Research Laboratoy University of Campinas – UNICAMP Hospital de Base de Brasília Hospital Beneficência Portuguesa de São Paulo (BP) Division of Nephrology School of Medicine of Ribeirão Preto University of Sao Paulo Hospital Santa Marcelina Hospital Universitário de Brasília University of Brasília - UnB, DF Hospital São Francisco na Providência de Deus Department of Internal Medicine Universidade Estadual Paulista-UNESP

To contribute to updating the recommendations for brain-dead potential organ donor management.A group of 27 experts, including intensivists, transplant coordinators, transplant surgeons, and epidemiologists, answered questions related to the following topics were divided into mechanical ventilation, hemodynamics, endocrine-metabolic management, infection, body temperature, blood transfusion, and checklists use. The outcomes considered were cardiac arrests, number of organs removed or transplanted as well as function / survival of transplanted organs. The quality of evidence of the recommendations was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system to classify the recommendations.A total of 19 recommendations were drawn from the expert panel. Of these, 7 were classified as strong, 11 as weak and 1 was considered a good clinical practice.Despite the agreement among panel members on most recommendations, the grade of recommendation was mostly weak.Fornecer recomendações para nortear o manejo clínico do potencial doador em morte encefálica.O presente documento foi formulado em dois painéis compostos por uma força tarefa integrada por 27 especialistas de diferentes áreas que responderam a questões dirigidas aos seguintes temas: ventilação mecânica, hemodinâmica, suporte endócrino-metabólico, infecção, temperatura corporal, transfusão sanguínea, e uso de checklists. Os desfechos considerados foram: parada cardíaca, número de órgãos retirados ou transplantados e função/sobrevida dos órgãos transplantados. A qualidade das evidências das recomendações foi avaliada pelo sistema Grading of Recommendations Assessment, Development, and Evaluation.Foram geradas 19 recomendações a partir do painel de especialistas. Dessas, 7 foram classificadas como fortes, 11 fracas e uma foi considerada boa prática clínica.Apesar da concordância entre os membros do painel em relação à maior parte das recomendações, o grau de recomendação é fraco em sua maioria.

Atualmente, os avanços na terapia imunossupressora em transplantes renais permitem que se individualize o regime de imunossupressão de acordo com as características dos pacientes. A avaliação individualizada do risco leva em conta características do receptor, tais como idade, raça, compatibilidade HLA (antígenos leucocitários humanos), co-morbidades, risco imunológico (sensibilização para antígenos do sistema HLA e retransplantes) e transplantes de órgãos duplos. São também consideradas as características do doador, sendo as principais idade, função renal, co-morbidades e ser doador de critérios expandidos. De uma maneira geral, regimes imunossupressores mais potentes são utilizados em receptores de alto risco imunológico, e regimes menos nefrotóxicos, nos receptores de baixo risco imunológico ou nos que recebem rins de doadores não-ideais. The advances in immunosuppressive therapy currently allow the individualization of immunosuppressive regimens according to the characteristics of kidney transplant recipients. Age, race, HLA (human leukocyte antigens) matching, comorbid conditions, immunological risk (HLA sensitization and retransplantation) and double organ transplants are the main recipient risk factors. Donor characteristics such as age, renal function, comorbid conditions and expanded criteria donors are also considered. More intensive immunosuppressive regimens are usually used for recipients with high immunological risk and less nephrotoxic regimens are offered to lower immunological risk patients and for expanded criteria donor recipients.

Background Renal transplantation is the best modality of renal replacement therapy for patients with end-stage renal disease. However, it is associated with weight gain and metabolic abnormalities, which adversely impact transplant outcomes. Objective The objective of this study was to identify the risk factors of one-year weight gain after renal transplantation. Methods A retrospective cohort study was conducted with 374 patients that underwent kidney transplantation between January 2006 and July 2013. Clinical and laboratory variables were collected from electronic records, and the outcome of interest was weight gain during the first year after renal transplantation. The data were reported as mean ± standard deviation, median (interquartile range) or number of subjects (%). The association between variables were assessed via chi-square test and ANOVA. For analysis of risk factors related to the outcomes of interest, multivariable logistic regression models were used. Results There were 181 (48.4%) female patients, 334 (89.3%) with white ethnicity and the mean age was 44.4 ± 12.8 years. The mean BMI pre-transplant was 24.7 ± 4.1 kg/m2, and 35 (9.9%) patients were classified as obese; 119 (33.6%) as overweight; 187 (52.8%) as normal weight; and 13 (3.7%) as malnourished. After one year of follow-up, the mean BMI was 26.2 ± 5.0 kg/m2, and 61 (17.3%) patients were classified as obese; 133 (37.8%) as overweight; 148 (42.0%) as normal weight; and 10 (2.8%) as malnourished. Weight gain was observed in 72.7% patients, and the average increase was 7.12 ± 5.9 kg. The female gender, lower pre-transplant body weight, lower number of hospitalizations, and a kidney received from a living donor were associated with weight gain by more than 5% in the first year post-transplant. Conclusion: Female gender and lower pre-transplant body weight were independently associated with weight gain by more than 5% in the first year after kidney transplantation; lower rates of hospitalization and donation from living donors were also risk factors for this outcome.

Additional file 2. Declaration of competing interests.

Additional file 1. Working group and contributions of each participant.

Additional file 3. Checklist for clinical management of brain-dead potential organ donor.

Introduction: BK virus (BKV) infection in renal transplant patients may cause kidney allograft dysfunction and graft loss. Accurate determination of BKV viral load is critical to prevent BKV-associated nephropathy (BKVAN) but the cut-off that best predicts BKVAN remains controversial. Objective: To evaluate the performance of a commercial and an in-house qPCR test for quantitative detection of BK virus in kidney transplant recipients. Methods: This was a prospective study with kidney transplant recipients from two large university hospitals in Brazil. Patients were screened for BKV infection every 3 months in the first year post-transplant with a commercial and an in-house real time polymerase chain reaction (qPCR) test. BKVAN was confirmed based on histopathology. The area under the curve for plasma qPCR was determined from receiver operating characteristic analysis. Results: A total of 200 patients were enrolled. Fifty-eight percent were male, 19.5% had diabetes mellitus, and 82% had the kidney transplanted from a deceased donor. BKV viremia was detected in 32.5% and BKVAN was diagnosed in 8 patients (4%). BKVAN was associated with viremia of 4.1 log copies/mL, using a commercial kit. The cut-off for the in-house assay was 6.1 log copies/mL. The linearity between the commercial kit and the in-house assay was R2=0.83. Conclusion: Our study shows that marked variability occurs in BKV viral load when different qPCR methodologies are used. The in-house qPCR assay proved clinically useful, a cheaper option in comparison to commercial qPCR kits. There is an urgent need to make BKV standards available to the international community. Resumo Introdução: A infecção pelo vírus BK (BKV) em pacientes de transplante renal pode levar a disfunção do aloenxerto renal e perda do enxerto. A determinação precisa da carga viral do BKV é fundamental para prevenir a nefropatia associada ao BKV (BKVAN), mas o ponto de corte de melhor valor preditivo para BKVAN ainda é foco de debates. Objetivo: Avaliar o desempenho de um teste de qPCR comercial e outro desenvolvido internamente para detecção quantitativa de vírus BK em receptores de transplante renal. Métodos: O presente estudo prospectivo incluiu receptores de transplante renal de dois grandes hospitais universitários no Brasil. Os pacientes foram testados para infecção por BKV a cada três meses no primeiro ano pós-transplante com um teste comercial de reação em cadeia de polimerase quantitativa em tempo real (qPCR) e outro desenvolvido internamente. A presença de BKVAN foi confirmada com base na histopatologia. A área sob a curva para o qPCR plasmático foi determinada a partir da análise da característica de operação do receptor. Resultados: Um total de 200 pacientes foram incluídos. Cinquenta e oito por cento eram do sexo masculino, 19,5% tinham diabetes mellitus e 82% tiveram seus rins transplantados de doadores falecidos. Viremia de BKV foi detectada em 32,5% dos pacientes e oito (4%) foram diagnosticados com BKVAN. BKVAN foi associada a viremia de 4,1 log cópias/mL usando o kit comercial. O corte para o ensaio interno foi de 6,1 log cópias/mL. A linearidade entre o kit comercial e o ensaio interno foi R2 = 0,83. Conclusão: Nosso estudo demonstrou uma acentuada variabilidade na carga viral de BKV quando diferentes metodologias de qPCR foram utilizadas. O ensaio interno de qPCR mostrou-se clinicamente útil, além de ser uma opção menos onerosa em relação aos kits comerciais de qPCR. Há uma necessidade urgente de se definir padrões de BKV para a comunidade internacional.

Introduction: Posterior reversible leukoencephalopathy syndrome (PRES) was first described by Hinchey in 1996. The syndrome is characterized by altered level of consciousness, headache, visual changes, and seizures associated with a vasogenic edema of the white matter that occurs predominantly in the occipital and parietal lobes. Imaging tests such as computed tomography (CT) and especially magnetic resonance imaging (MRI) support the diagnosis. Case Report: We report a case of a 48-year-old female patient who underwent a deceased donor kidney transplant and received tacrolimus as a part of the immunosuppressive regimen. Five weeks after transplantation she was admitted to the emergency due to sudden onset of confusion, disorientation, visual disturbances, and major headache. PRES was suspected and the diagnosis confirmed by brain MRI. Tacrolimus was withdrawn and rapid improvement of the neurological signs occurred leading to the conclusion that this drug triggered the syndrome. Conclusion: PRES is an unusual complication after organ transplantation and should be considered in the appropriate clinical setting. Physicians must be aware of this condition in order to provide early detection and appropriate treatment since delay in removing the cause may lead to permanent sequelae.

Objetivo: Investigar a correlação entre a contagem de linfócitos totais e células T CD3+ no sangue periférico em receptores de transplante renal submetidos a tratamento com globulina antitimocitária, e discutir resultados relacionados. Métodos: Estudo retrospectivo de centro único envolvendo 226 pacientes submetidos a transplante renal entre 2008 e 2013 e tratados com globulina antitimocitária, para fins de indução ou tratamento de rejeição celular. As doses foram ajustadas de acordo com a contagem de células T CD3+ ou linfócitos totais no sangue periférico. Resultados: No total, 664 amostras pareadas foram analisadas. O coeficiente de correlação de Spearman para as amostras em geral foi de 0,416 (p20 células/mm³. Conclusão: A contagem de linfócitos totais no sangue periférico não substitui a contagem de células T CD3+ enquanto estratégia de monitorização da terapia à base de globulina antitimocitária. Objective: To investigate the correlation between total lymphocyte and CD3+ T cell counts in peripheral blood in renal transplant patients treated with anti-thymocyte globulin, and discuss related outcomes. Methods: A single-center, retrospective study involving 226 patients submitted to kidney transplant between 2008 and 2013, and treated with anti-thymocyte globulin for induction or treatment of cellular rejection. Doses were adjusted according to CD3+ T cell or total lymphocyte counts in peripheral blood. Results: A total of 664 paired samples were analyzed. The Spearman’s correlation coefficient was 0.416 (p20 cells/mm³. Conclusion: Total lymphocyte and CD3+ T cell counts in peripheral blood are not equivalent monitoring strategies in anti-thymocyte globulin therapy

Background: Long-term outcomes in kidney transplantation (KT) have not significantly improved during the past twenty years. Despite being a leading cause of graft failure, glomerular disease (GD) recurrence remains poorly understood, due to heterogeneity in disease pathogenesis and clinical presentation, reliance on histopathology to confirm disease recurrence, and the low incidence of individual GD subtypes. Large, international cohorts of patients with GD are urgently needed to better understand the disease pathophysiology, predictors of recurrence, and response to therapy. Methods: The Post-TrANsplant GlOmerular Disease (TANGO) study is an observational, multicenter cohort study initiated in January 2017 that aims to: 1) characterize the natural history of GD after KT, 2) create a biorepository of saliva, blood, urine, stools and kidney tissue samples, and 3) establish a network of patients and centers to support novel therapeutic trials. The study includes 15 centers in America and Europe. Enrollment is open to patients with biopsy-proven GD prior to transplantation, including IgA nephropathy, membranous nephropathy, focal and segmental glomerulosclerosis, atypical hemolytic uremic syndrome, dense-deposit disease, C3 glomerulopathy, complement- and IgG-positive membranoproliferative glomerulonephritis or membranoproliferative glomerulonephritis type I-III (old classification). During phase 1, patient data will be collected in an online database. The biorepository (phase 2) will involve collection of samples from patients for identification of predictors of recurrence, biomarkers of disease activity or response to therapy, and novel pathogenic mechanisms. Finally, through phase 3, we will use our multicenter network of patients and centers to launch interventional studies. Discussion: Most prior studies of post-transplant GD recurrence are single-center and retrospective, or rely upon registry data that frequently misclassify the cause of kidney disease. Systematically determining GD recurrence rates and predictors of clinical outcomes is essential to improving post-transplant outcomes. Furthermore, accurate molecular phenotyping and biomarker development will allow better understanding of individual GD pathogenesis, and potentially identify novel drug targets for GD in both native and transplanted kidneys. The TANGO study has the potential to tackle GD recurrence through a multicenter design and a comprehensive biorepository.