RESUMO
Data from the general population suggest that fatality rates declined during the course of the pandemic. This analysis, using data extracted from the Brazilian Kidney Transplant COVID-19 Registry, seeks to determine fatality rates over time since the index case on March 3rd, 2020. Data from hospitalized patients with RT-PCR positive SARS-CoV-2 infection from March to August 2020 (35 sites, 878 patients) were compared using trend tests according to quartiles (Q1: <72 days; Q2: 72-104 days; Q3: 105-140 days; Q4: >140 days after the index case). The 28-day fatality decreased from 29.5% (Q1) to 18.8% (Q4) (pfor-trend = 0.004). In multivariable analysis, patients diagnosed in Q4 showed a 35% reduced risk of death. The trend of reducing fatality was associated with a lower number of comorbidities (20.7-10.6%, p for-trend = 0.002), younger age (55-53 years, pfor-trend = 0.062), and better baseline renal function (43.6-47.7 ml/min/1.73 m2, pfor-trend = 0.060), and were confirmed by multivariable analysis. The proportion of patients presenting dyspnea (pfor-trend = 0.001) and hypoxemia (pfor-trend < 0.001) at diagnosis, and requiring intensive care was also found reduced (pfor-trend = 0.038). Despite possible confounding variables and time-dependent sampling differences, we conclude that COVID-19-associated fatality decreased over time. Differences in demographics, clinical presentation, and treatment options might be involved.
Assuntos
COVID-19 , Transplante de Rim , Estudos de Coortes , Humanos , Transplante de Rim/efeitos adversos , Sistema de Registros , SARS-CoV-2 , TransplantadosRESUMO
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
Signal variation is a common drawback in untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS), mainly due to the complexity of biological matrices and reduced sample preparation, which results in the accumulation of sample components in the column and the ion source. Here we propose a simple, easy to implement approach to improve data quality in untargeted metabolomics by LC-MS. This approach involves the use of a divert valve to direct the column effluent to waste at the beginning of the chromatographic run and during column cleanup and equilibration, in combination with longer column cleanups in between injections. Our approach was tested using urine samples collected from patients after renal transplantation. Analytical responses were contrasted before and after introducing these modifications by analyzing a batch of untargeted metabolomics data. A significant improvement in peak area repeatability was observed for the quality controls, with relative standard deviations (RSDs) for several metabolites decreasing from â¼60% to â¼10% when our approach was introduced. Similarly, RSDs of peak areas for internal standards improved from â¼40% to â¼10%. Furthermore, calibrant solutions were more consistent after introducing these modifications when comparing peak areas of solutions injected at the beginning and the end of each analytical sequence. Therefore, we recommend the use of a divert valve and extended column cleanup as a powerful strategy to improve data quality in untargeted metabolomics, especially for very complex types of samples where minimum sample preparation is required, such as in this untargeted metabolomics study with urine from renal transplanted patients.
Assuntos
Cromatografia Líquida , Confiabilidade dos Dados , Espectrometria de Massas , Metabolômica , Urinálise , Humanos , Urinálise/métodos , Urinálise/normas , Urina/químicaRESUMO
Background: The implications of ligating the native ureter without ipsilateral nephrectomy after primary kidney transplant pyeloureterostomy (PU) have been described previously. Methods: This single-center retrospective cohort study including 4,215 kidney transplants performed between February 2010 and December 2014, analyzed urological complications following primary (P-PU) and secondary (S-PU) pyeloureterostomy used to treat urological leaks (UL-PU) and ureteral stenosis (US-PU) without concomitant ipsilateral nephrectomy, in a large cohort of patients. Results: There were 495 (11.7%) pyeloureterostomy with native ureter ligation without nephrectomy, 409 P-PU (82.6%) and 86 S-PU (17.4%), of which 76 were UL-PU and 10 were US-PU. The median follow-up was 33.8 months. The incidence of native ipsilateral kidney complications requiring nephrectomy was 2.02% (n = 10). Urinary leak was diagnosed in 3.6% of patients after P-UP and 9.2% after UL-PU. Ureteral stenosis was diagnosed in 1.7% of patients after P-UP, 3.9% after UL-PU and 10% after US-PU. Conclusion: This cohort analysis suggests that native ureter ligation during pyeloureterostomy without native nephrectomy is associated with low incidence of clinically indicated ipsilateral native nephrectomy. Caution and awareness should be emphasized in patients with history of ADPKD and neurogenic augmented bladders.
Assuntos
Transplante de Rim , Ureter , Humanos , Rim , Transplante de Rim/efeitos adversos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Ureter/cirurgiaRESUMO
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.
Resumo A Readmissão Hospitalar Precoce (RH), definida como todas as readmissões dentro de 30 dias após a alta hospitalar inicial, é uma métrica da qualidade hospitalar. É influenciada pelas características demográficas da população em risco, pela abordagem multidisciplinar da alta hospitalar inicial, pelo acesso, pela cobertura e pela abrangência do Sistema de Saúde e pelas políticas de reembolso. A readmissão hospitalar precoce está associada a maior morbidade, mortalidade e aumento dos custos com saúde. O monitoramento da RH permite a identificação das fragilidades hospitalares e ambulatoriais e a implementação de intervenções corretivas. Entre os receptores de transplante renal nos EUA, a RH varia entre 18% e 47% e está associada a maior mortalidade e perda do enxerto no primeiro ano do transplante. Um estudo no Brasil mostrou uma incidência de 19,8% de RH. As principais causas de readmissão foram infecções e complicações cirúrgicas e metabólicas. As estratégias para reduzir a readmissão hospitalar precoce são, portanto, essenciais e devem considerar o ambiente local, incluindo condições socioeconômicas, epidemiologia local, doenças e mobilidade endêmicas.
Assuntos
Humanos , Masculino , Feminino , Adulto , Readmissão do Paciente/estatística & dados numéricos , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Transplante de Rim/estatística & dados numéricos , Alta do Paciente , Readmissão do Paciente/tendências , Brasil/epidemiologia , Incidência , Fatores de Risco , Seguimentos , Atenção à Saúde/economia , Comunicação Interdisciplinar , Transplantados/estatística & dados numéricos , Sobrevivência de Enxerto , Infecções/complicações , Reembolso de Seguro de Saúde/legislação & jurisprudência , Doenças Metabólicas/epidemiologiaRESUMO
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.
Assuntos
Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Transplante de Rim/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Adulto , Brasil/epidemiologia , Atenção à Saúde/economia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Incidência , Infecções/complicações , Infecções/epidemiologia , Reembolso de Seguro de Saúde/legislação & jurisprudência , Comunicação Interdisciplinar , Transplante de Rim/economia , Masculino , Doenças Metabólicas/complicações , Doenças Metabólicas/epidemiologia , Pessoa de Meia-Idade , Alta do Paciente , Readmissão do Paciente/economia , Readmissão do Paciente/tendências , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Transplantados/estatística & dados numéricosRESUMO
Measurement of immunosuppressive drug concentrations cyclosporine A (CyA), tacrolimus (TAC), sirolimus (SIR), and everolimus (EVE) in blood is an important application of therapeutic drug monitoring. These immunosuppressive agents are used in combined regimens and nowadays the liquid chromatography and tandem mass spectrometry is the best option for simultaneous analysis of these drugs in one short run. We developed an liquid chromatography and tandem mass spectrometry methodology in-house to measure the combination of immunosuppressants in a single blood sample from transplant patients in Brazil. We analyzed 235 combinations of 4 immunosuppressive drugs in patient blood to validate this study. The measuring ranges were 9 to 1000 ng/mL for CyA and 2 to 50 ng/mL for TAC, SIR, and EVE. Accuracy of the method was between 83.87% and 126.6% (coefficient of determination [r2] > 0.995). Validation of variation was ≤15% for lower limit of quantification. In our analysis 20% of patients treated with EVE showed concentration range of 6 to 6.9 ng/mL, 28% of patients treated with SIR showed a concentration range of 4 to 4.9 ng/mL to TAC, 22% of patients showed concentration range of 5 to 5.9 ng/mL, and finally 50% of patients treated with CyA showed concentration range of 20 to 30 ng/mL. Our routine laboratory was able to implement this new methodology in-house to measure simultaneous CyA, TAC, SIR, and EVE in a single blood sample from transplant patients with a sensibility and rapid quantification analysis.
Assuntos
Cromatografia Líquida/métodos , Monitoramento de Medicamentos/métodos , Imunossupressores/sangue , Espectrometria de Massas em Tandem/métodos , Brasil , Ciclosporina/sangue , Everolimo/sangue , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Transplante de Órgãos/efeitos adversos , Sirolimo/sangue , Tacrolimo/sangueRESUMO
INTRODUCTION: Thrombotic microangiopathy (TMA) in post-transplant setting has heterogeneous clinical manifestations. METHODS: We retrospectively studied data of 89 patients with post-transplant TMA, which was characterized by thrombi in at least one glomerulus and/or arteriole. Systemic TMA was defined by thrombocytopenia and microangiopathic anemia and early onset TMA, when occurred less than 90 days post transplant. RESULTS: The cumulative incidence was 0.93%. The majority of the recipients were young (mean age 39 years), female (52%) and Caucasian (48%) with primary kidney disease of unknown etiology (37%). Early TMA occurred in 51% of the patients and systemic TMA, in 25%. Underlying precipitating factors were: infection (54%), acute rejection (34%), calcineurin inhibitor toxicity (13%) and pregnancy (3%). 18% of the patients had several triggers. Glomerular TMA was observed in 50% of the biopsies and endothelial cell activation, in 61%. The 1-year patient survival was 97% and corresponding graft survival, 66%. Allograft survival was inferior when acute antibody mediated rejection (ABMR) occurred (with 41%; without 70%, p = 0.01), however no differences were determined by hemolysis, time of onset, thrombi location or endothelial cell activation. CONCLUSIONS: Our results suggest that post-transplant TMA is a rare but severe condition, regardless of its clinical and histological presentation, mainly when associated to ABMR.
Assuntos
Transplante de Rim/efeitos adversos , Microangiopatias Trombóticas/etiologia , Adulto , Feminino , Rejeição de Enxerto/complicações , Rejeição de Enxerto/imunologia , Humanos , Incidência , Infecções/complicações , Nefropatias/complicações , Nefropatias/terapia , Masculino , Pessoa de Meia-Idade , Gravidez , Estudos Retrospectivos , Microangiopatias Trombóticas/patologia , Transplante Homólogo/efeitos adversosRESUMO
OBJECTIVES: To describe the incidence of cytomegalovirus (CMV) infection/disease in kidney transplant recipients receiving an mTOR-inhibitor-containing immunosuppressive regimen without prophylactic CMV treatment. METHODS: This single-center retrospective cohort analysis included all de novo kidney transplant recipients (09/15/2015-07/31/2017) receiving 3 mg/kg single dose of rabbit antithymocyte globulin induction, tacrolimus, everolimus, and prednisone. Preemptive therapy was initiated only in patients deemed at higher risk for CMV infection: (a) D+/R- CMV patients; (b) after treatment for acute rejection (ARt); and (c) after everolimus discontinuation (EVRd). RESULTS: Of 230 patients, there were no episodes of CMV disease among 217 (94%) without criteria to initiate preemptive therapy. Of 77 (33.5%) patients initiating preemptive therapy, 13 were D+/R-, 30 were ARt, and 34 were EVRd. The overall incidence of first CMV infection/disease was 6% (46.1% in D+/R-, 13.3% ARt [all patients had also discontinued everolimus], and 11.8% after early [<90 days] EVRd). The incidence of biopsy-proven acute rejection was 5.6%, and median glomerular filtration rate at month 12 was 47 mL/min/1.73m2 . One-year patient and death-censored graft survivals were 97.4% and 98.1%. CONCLUSION: This study suggests that everolimus-containing immunosuppressive regimen reduces the need for preventive strategies for CMV infection in the majority of kidney transplant recipients, reducing antiviral drug-associated toxicities and healthcare-related expenditures.
Assuntos
Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/isolamento & purificação , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Soro Antilinfocitário/administração & dosagem , Brasil/epidemiologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/microbiologia , Everolimo/administração & dosagem , Feminino , Seguimentos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prednisona/administração & dosagem , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Tacrolimo/administração & dosagemRESUMO
The optimal immunosuppressive regimen for recipients of expanded criteria donor (ECD) kidneys has not been identified. In this single-center study, 171 recipients of ECD kidney transplants were randomized to receive antithymocyte globulin induction, and delayed introduction of reduced dose tacrolimus, prednisone and everolimus (r-ATG/EVR, n = 88), or mycophenolate (r-ATG/MPS, n = 83). No cytomegalovirus (CMV) pharmacological prophylaxis was used. The primary endpoint was the incidence of CMV infection/disease at 12 months. Secondary endpoints included treatment failure [first biopsy-proven acute rejection (BPAR), graft loss, or death] and safety. Patients treated with EVR showed a 89% risk reduction (13.6 vs. 71.6%; HR 0.11, 95% CI 0.06-0.220, P < 0.001) in the incidence of first CMV infection/disease. Incidences of BPAR (16% vs. 5%, P = 0.021), graft loss (11% vs. 1%, P = 0.008), death (10% vs. 1%, P = 0.013), and treatment discontinuation (40% vs. 28%, P = 0.12) were higher in the r-ATG/EVR, leading to premature study termination. Mean glomerular filtration rate was lower in r-ATG/EVR (31.8 ± 18.8 vs. 42.6 ± 14.9, P < 0.001). In recipients of ECD kidney transplants receiving no CMV pharmacological prophylaxis, the use of everolimus was associated with higher treatment failure compared with mycophenolate despite the significant reduction in the incidence of CMV infection/disease (ClinicalTrials.gov.NCT01895049).