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IntroductionThe combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF.MethodsMulticenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection (“match”) was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI.ResultsThe global analysis (n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2.DiscussionThe regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.

Existe tendência de aumento do número de casos de infecção por bactérias multirresistentes, tendo em vista o uso indiscriminado e, por vezes, excessivo de antibióticos de amplo espectro no ambiente hospitalar. Essas infecções geraram grande impacto, principalmente em pacientes imunossuprimidos submetidos ao transplante de órgãos sólidos. Dados nacionais revelaram aumento significativo das taxas de infecções por bactérias multirresistentes. O presente estudo teve como objetivo avaliar a incidência e demografia das infecções relacionadas à assistência à saúde por Klebsiella pneumoniae produtora de carbapenemase (KPC). Este é um estudo observacional, retrospectivo, descritivo, realizado em centro único (Hospital do Rim) com avaliação dos desfechos de receptores de transplante renal com infecção por KPC entre novembro de 2009 e dezembro de 2015. Em nosso centro, infecção de corrente sanguínea por KPC teve maior prevalência, seguida de infecção do trato urinário. A mortalidade geral em 30 dias foi de 36%, semelhante à encontrada na literatura internacional. A infecção por bactérias multirresistentes é uma condição clínica grave em pacientes transplantados e constitui um desafio terapêutico.

Abstract Early hospital readmission (EHR), defined as all readmissions within 30 days of initial hospital discharge, is a health care quality measure. It is influenced by the demographic characteristics of the population at risk, the multidisciplinary approach for hospital discharge, the access, coverage, and comprehensiveness of the health care system, and reimbursement policies. EHR is associated with higher morbidity, mortality, and increased health care costs. Monitoring EHR enables the identification of hospital and outpatient healthcare weaknesses and the implementation of corrective interventions. Among kidney transplant recipients in the USA, EHR ranges between 18 and 47%, and is associated with one-year increased mortality and graft loss. One study in Brazil showed an incidence of 19.8% of EHR. The main causes of readmission were infections and surgical and metabolic complications. Strategies to reduce early hospital readmission are therefore essential and should consider the local factors, including socio-economic conditions, epidemiology and endemic diseases, and mobility.

Coronavirus disease 2019 (COVID-19) was first reported in late December 2019 in Wuhan, China. The etiological agent of this disease is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the high transmissibility of the virus led to its rapid global spread and a major pandemic (ongoing at the time of writing this review). The clinical manifestations of COVID-19 can vary widely from non-evident or minor symptoms to severe acute respiratory syndrome and multi-organ damage, causing death. Acute kidney injury (AKI) has been recognized as a common complication of COVID-19 and in many cases, kidney replacement therapy (KRT) is required. The presence of kidney abnormalities on hospital admission and the development of AKI are related to a more severe presentation of COVID-19 with higher mortality rate. The high transmissibility and the broad spectrum of clinical manifestations of COVID-19 are in part due to the high affinity of SARS-CoV-2 for its receptor, angiotensin (Ang)-converting enzyme 2 (ACE2), which is widely expressed in human organs and is especially abundant in the kidneys. A debate on the role of ACE2 in the infectivity and pathogenesis of COVID-19 has emerged: Does the high expression of ACE2 promotes higher infectivity and more severe clinical manifestations or does the interaction of SARS-CoV-2 with ACE2 reduce the bioavailability of the enzyme, depleting its biological activity, which is closely related to two important physiological systems, the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), thereby further contributing to pathogenesis. In this review, we discuss the dual role of ACE2 in the infectivity and pathogenesis of COVID-19, highlighting the effects of COVID-19-induced ACE2 depletion in the renal physiology and how it may lead to kidney injury. The ACE2 downstream regulation of KKS, that usually receives less attention, is discussed. Also, a detailed discussion on how the triad of symptoms (respiratory, inflammatory, and coagulation symptoms) of COVID-19 can indirectly promote renal injury is primary aborded.

Resumo Introdução: A sensibilização está associada a piores desfechos clínicos após o transplante renal (TxR), incluindo maior incidência de função tardia, rejeição aguda e perda do enxerto. Objetivos: Avaliar os desfechos de eficácia e segurança de 1 ano de receptores de TxR com doador falecido sensibilizados induzidos com globulina antitimócito (ATG) e compará-las aos de pacientes não sensibilizados. Métodos: Receptores de TxR com doador falecido entre janeiro de 1998 e dezembro de 2009 foram divididos em 5 grupos: grupo controle 1 - n = 89, PRA negativo, sem indução; grupo controle 2 - n = 94, PRA negativo, indução com basiliximabe; grupo controle 3 - n = 81, PRA negativo, indução com ATG; grupo teste 4 - n = 64, PRA 1-49%, indução com ATG; grupo teste 5 - n = 118, PRA ≥ 50%, indução com ATG. Resultados: Não houve diferença na incidência de rejeição entre pacientes sensibilizados e não sensibilizados, exceto pelo grupo 1, que apresentou a maior incidência de rejeição aguda comprovada por biópsia (20,2%, p = 0,006 vs. grupo 4 ep = 0,001 vs. grupo 5). Os pacientes sensibilizados induzidos com ATG apresentaram maior incidência de infecção por citomegalovírus quando comparados aos pacientes do grupo 2 (26,6% e 14,4% vs. 2,1%). Não houve diferença nas sobrevidas do enxerto e do paciente. Na análise multivariada, PRA > 50% e uso de ATG não foram associados à perda, perda com óbito censorado ou óbito. Conclusão: Os pacientes sensibilizados induzidos com ATG apresentaram incidência de rejeição semelhante ou inferior à de pacientes não sensibilizados não induzidos. Estes pacientes apresentaram sobrevidas do enxerto e do paciente semelhantes em 1 ano e comparável perfil de segurança.

Resumo Introdução: O número de pacientes idosos portadores de doença renal crônica aumenta progressivamente, desafiando os algoritmos de alocação, em um cenário de escassez de órgãos para transplante. Objetivo: Avaliar o impacto da idade sobre os resultados do transplante renal. Métodos: Foram analisados todos os 366 pacientes > 60 anos transplantados entre 1998-2010 versus um grupo controle de 366 pacientes mais jovens pareados por gênero, tipo de doador (vivo/falecido) e ano do transplante. Resultados: Diabetes mellitus (HR 1,5; IC 1,0-2,2; p = 0,031) e doador falecido (HR 1,7; IC 1,2-2,7; p = 0,013) se associaram independentemente a maior risco de óbito. Diabetes mellitus (HR 1,8; IC 1,2-2,6; p = 0,003) e priorização por acesso vascular (HR 2,9; IC 1,2-2,6; p < 0,001), mas não idade, foram fatores independentes de perda do enxerto renal. Conclusão: A idade avançada não teve impacto negativo no resultado do transplante quando excluído óbito do paciente como causa de perda do enxerto. A maior mortalidade entre a população senil esteve associada à maior frequência de comorbidades, em especial diabetes mellitus.

Epicardial fat (EF) has been related to increased cardiovascular risk in chronic kidney disease patients. Kidney transplantation is associated with weight gain, especially within the first 12 months. Recently an association between EF and left ventricular mass (LVM) has been suggested in kidney transplant (KTX) recipients.Evaluate the EF in KTX recipients and its association with cardiovascular parameters in a 12-month follow-up study.EF volume was determined using thoracic computed tomography. The EF progressor group (EF gain) was defined by any increment in EF after 12 months. LVM and LVM index were calculated by echocardiography.Ninety-eight incident KTX patients [57% men, 41.2 ± 10.1 years, mean dialysis time prior to transplant of 24 (11-60) months] were analyzed. At baseline and after 12 months, EF was 318.6 (275.2-392.6) ml and 329.5 (271.7-384.8) ml, respectively (p = 0.03). When compared to patients who EF decreased (n = 33), those with EF gain (n = 65) had a greater increase of body mass index, abdominal circumference and blood glucose. These patients also had a lower reduction of LVM index. However in the multivariate analysis, there was no difference in LVM index change between groups (interaction p = 0.565), even after adjustment for hypertension, glucose and coronary calcium score (interaction p = 0.538).The impact of EF gain on ventricular mass after KTX could not be definitely confirmed. Further prospective studies in a large sample of KTX patients should be considered to address a possible causal relationship between EF gain and cardiac hypertrophy in this population.

Fundamentos: Atualmente, a revascularização cirúrgica do miocárdio é o melhor tratamento para o paciente dialítico com lesão coronariana multiarterial, contudo a mortalidade e a morbidade hospitalar do procedimento ainda permanecem altas. Objetivos: Avaliar os resultados e a evolução intra-hospitalar da revascularização cirúrgica do miocárdio isolada em pacientes dialíticos. Métodos: Estudo retrospectivo unicêntrico de 50 pacientes dialíticos consecutivos e não selecionados, submetidos à revascularização cirúrgica do miocárdio em um hospital terciário universitário no período de 2007 a 2012. Resultados: A casuística apresentou alta prevalência de fatores de risco cardiovasculares (100% hipertensos, 68% diabéticos e 40% dislipidêmicos). Não houve óbito intraoperatório, e 60% dos procedimentos foram feitos sem circulação extracorpórea. Houve sete (14%) óbitos intra-hospitalares. Infecção pós-operatória, insuficiência cardíaca prévia, uso de circulação extracorpórea, função ventricular anormal e reexploração cirúrgica foram os fatores associados a maior mortalidade. Conclusão: A revascularização cirúrgica do miocárdio é um procedimento factível para essa classe de pacientes, contudo com alta morbidade e mortalidade intra-hospitalar. É necessário melhor entendimento das particularidades metabólicas desses pacientes para o planejamento adequado das condutas.

BACKGROUND:Coronary calcification (CAC) is highly prevalent in kidney transplant recipients (KTRs) and has been associated with cardiovascular morbidity and mortality. Some studies have shown a reduction in CAC progression with statin therapy in the general and chronic kidney disease (CKD) populations. OBJECTIVES AND METHODS:The aim of the present study was to evaluate the effect of statins on CAC progression in incident kidney transplant recipients. Patients were randomly assigned to the statin (n = 61, 10 mg daily) and control group (n = 59). CAC and biochemical analyses were performed at baseline and 12 months. RESULTS:At baseline, CAC was observed in 30% and 21% of patients in the statin and control groups, respectively (p = 0.39). The calcium score at baseline and its absolute and relative changes over 12 months of follow up were similar among the groups. In the statin group, total cholesterol (p < 0.001), low density lipoprotein cholesterol (p < 0.001) and triglycerides (p = 0.005) decreased, and the estimated glomerular function rate increased (p

Tacrolimo de liberação modificada (TAC-MR) é uma nova formulação de (?) que permite a administração de uma dose única diária. Em voluntários sadios e em receptores de transplante de rim e fígado, a exposição ao tacrolimo (ASC – área sob a curva da concentração durante o intervalo de dosagem) e as concentrações residuais foram semelhantes após a administração de TAC ou TAC-MR. A conversão de TAC para TAC-MR (1:1 mg) é eficaz e segura, utilizando a mesma estratégia de monitoramento e a mesma faixa terapêutica. A equivalência terapêutica entre TAC-MR e TAC foi comprovada em um estudo prospectivo, multicêntrico, randomizado e aberto que incluiu 638 novos receptores de transplante renal. As médias das doses e das concentrações sanguíneas residuais de tacrolimo, a influência da etnia e a dificuldade para atingir a faixa terapêutica foram semelhantes entres os receptores de transplante renal que receberam TAC ou TAC-MR. Também não foram observadas diferenças na proporção de pacientes que apresentou falha de eficácia (desfecho composto por rejeição aguda comprovada por biópsia, perda do enxerto, óbito ou perda de seguimento) e no perfil de segurança. Os resultados desses estudos indicam que TAC-MR, administrado em dose única diária apresenta eficácia e segurança semelhante à do TAC, permitindo a utilização da mesma estratégia de monitoramento terapêutico. Estudos de seguimento prolongado são necessários para avaliar a influência de TAC- MR na adesão do paciente ao tratamento, bem como se as diferenças farmacocinéticas podem resultar em redução significativa de reações adversas, fatores com reconhecido impacto na sobrevida do paciente transplantado.

Objetivos: O anticorpo monoclonal anti-CD3 tem sido empregado na prevenção e tratamento de episódios de rejeição aguda em transplante de órgãos. Neste estudo retrospectivo, relatamos a experiência de três instituições brasileiras que utilizaram o anticorpo anti-CD3 produzido pelo Instituto Butantan (São Paulo, Brasil) em pacientes transplantados renais. Métodos: Foram analisados 25 pacientes que receberam anti-CD3 para profilaxia (n=9) e tratamento de rejeição celular aguda (n=16). Resultados: Os pacientes que utilizaram o anti- CD3 profilaticamente eram sensibilizados em sua maioria (89%) e apresentaram ocorrência de rejeição aguda em 33% dos casos. O uso terapêutico foi indicado para tratamento de rejeição córtico-resistente ou rejeições de maior severidade histológica, e reverteu clinicamente 69% dos episódios tratados. Na maioria dos pacientes, o uso do anti-CD3 Butantan reduziu o número de células CD3+ a valores menores que 30 cel/mm3 no segundo dia de tratamento. O evento adverso mais freqüentemente observado foi febre e infecções bacterianas e virais, seis meses após o tratamento, que foram observadas em 13 e 10 pacientes, respectivamente. No período médio de seguimento de oito anos nenhuma ocorrência de tumor foi relatada. Conclusões: Concluímos que a utilização do anti-CD3 Butantan mostrou-se eficaz na profilaxia e tratamento de rejeição aguda em pacientes transplantados renais.

Abstract Introduction: Women regain fertility a few time after renal transplantation. However, viability of pregnancy and maternal complications are still unclear. Objective: To describe the outcomes of pregnancies in kidney transplanted patients, focusing on maternal complications. Methods: Retrospective study of pregnancies in kidney transplanted patients between 2004 and 2014, followed up 12 months after delivery. Each pregnancy was considered an event. Results: There were 53 pregnancies in 36 patients. Mean age was 28 ± 5years. Pregnancy occurred 4.4 ± 3.0 years post-transplant. Immunosuppression before conception was tacrolimus, azathioprine, and prednisone in 74% of the cases. There were 15% miscarriages in the 1st trimester and 8% in 2nd trimester. In 41% of the cases, it was necessary to induce labor. From all births, 22% were premature and 17% very premature. There were 5% stillbirths and 5% of neonatal deaths. De novo proteinuria occurred in 60%, urinary tract infection in 23%, preeclampsia in 11%, acute rejection in 6%, and graft loss in 2% of the cases. It was observed a significant increase in creatinine at preconception comparing to 3rd trimester and follow-up (1.17 vs. 1.46 vs. 1.59 mg/dL, p < 0.001). Conclusion: Although the sample is limited, the number of miscarriages was higher than in the general population, with high rates of maternal complications. Sustained increase of creatinine suggests increased risk of graft loss in long-term.

BackgroundThis study evaluated the long-term effects of percutaneous intervention in children and adolescents with transplant renal artery stenosis (TRAS).MethodsTwenty patients had significant stenosis (>50%) and underwent percutaneous transluminal angioplasty (PTA/stenting) (TRAS group-intervention); 14 TNS (non-significant group -control) patients did not have significant stenosis (≤50%) and were treated clinically. The combined primary endpoints were death from all causes and late graft failure. The secondary endpoints were serum creatinine (SCr), systolic blood pressure (SBP), and diastolic blood pressure (DBP).ResultsNo statistically significant difference was found between TRAS-Intervention(N = 20) and TNS groups-Control (N = 14) for these clinical parameters: deaths, 1 (5.0%) vs. 0 (0.0%) (p = 1.000) and graft loss, 4 (20.0%) vs. 2 (14.3%) (p = 1.000). For the secondary endpoints, after 1 month and 1 year the values of SCr, SBP, and DBP were similar between the two groups but not statistically significant.DiscussionIn the TRAS group (intervention), the stent implantation was beneficial for treating refractory hypertension and reducing blood pressure (BP) in children and adolescents. Despite the outcomes being similar in the two groups, it can be inferred that the patients in the TRAS group (intervention) would have had a worse outcome without the percutaneous intervention.ConclusionTRAS treatment with stenting can be considered for children and adolescents. Because the sample in the present study comprised of only a specific population, further studies are needed for generalization.Trial registrationThe trial was registered at clinictrials.gov with trial registration number NCT04225338.

ABSTRACT Background Kidney transplant is the treatment of choice for patients with end-stage renal disease and is associated with lower mortality when compared to dialysis methods. Brazil is the country with the second largest number of kidney transplants in the world and among these patients it has been observed that liver abnormalities are common. The frequency of liver abnormalities ranges from 20-50% post-transplantation, and have an important impact on the survival and quality of life of these patients. There are scarce data about the frequency, causes and characteristics of these alterations. Objective To determine the prevalence of the different causes of hepatic abnormalities in kidney transplant recipients, to associate the characteristics of these abnormalities with demographic, epidemiological and clinical variables, to compare the characteristics of hepatic alterations between different etiologies, and to evaluate possible changes in diagnosis over two different periods of time. Methods Descriptive, cross-sectional observational, epidemiological study was conducted at the outpatient “Hepato-Rim”clinic of Hospital São Paulo (EPM/UNIFESP), a center providing specialized care for patients with hepatic abnormalities and underlying kidney diseases. Results Five-hundred eighty-one transplant patients were evaluated. The most prevalent etiologies of liver abnormalities were hepatitis C and B, iron overload, nonalcoholic fatty liver disease (NAFLD), and drug-induced liver injury (DILI). The most common cause — hepatitis C — was analyzed in greater detail. Compared to the other causes, this infection was more frequent in older patients, female patients, and patients with a longer time since transplantation and hemodialysis. Analysis of the two periods showed that patients of period 1 (P1 — 1993 to 2005) were older and were more frequently referred because of positive serology; referral due to aminotransferases abnormalities predominated during period 2 (P2 — 2006 to 2018). The predominant diagnoses were hepatitis C and B during P1 and NAFLD and DILI during P2. Conclusion Assessment of the main hepatic alterations in kidney transplant recipients is important because it permits better management of these patients in terms of diagnostic investigation and treatment and contributes to the prevention of complications in this special population.

Abstract Background Transplant renal artery stenosis (TRAS) is the main vascular complication of kidney transplantation. For research and treatment purposes, several authors consider critical renal artery stenosis to be greater than 50%, and percutaneous intervention is indicated in this scenario. However, there are no reports in the current literature on the evolution of patients with less than 50% stenosis. Method This retrospective study included data from all patients who underwent kidney transplantation and were suspected of having TRAS after transplantation with stenosis under 50% independent of age and were referred for angiography at a single centre between January 2007 and December 2014. Results During this period, 6,829 kidney transplants were performed at Hospital do Rim, 313 of whom had a clinical suspicion of TRAS, and 54 of whom presented no significant stenosis. The average age was 35.93 years old, the predominant sex was male, and most individuals (94.4%) underwent dialysis before transplantation. In most cases in this group, transplants occurred from a deceased donor (66.7%). The time between transplantation and angiography was less than one year in 79.6% of patients, and all presented nonsignificant TRAS. Creatinine levels, systolic blood pressure, diastolic blood pressure and glomerular filtration rate improved over the long term. The outcomes found were death and allograft loss. Conclusion Age, sex and ethnic group of patients were factors that did not interfere with the frequency of renal artery stenosis. The outcomes showed that in the long term, most patients evolve well and have improved quality of life and kidney function, although there are cases of death and kidney loss.