RESUMO
Predicting risk factors for death in leptospirosis is challenging, and identifying high-risk patients is crucial as it might expedite the start of life-saving supportive care. Admission data of 295 leptospirosis patients were enrolled, and a machine-learning approach was used to fit models in a derivation cohort. The comparison of accuracy metrics was performed with two previous models-SPIRO score and quick SOFA score. A Lasso regression analysis was the selected model, demonstrating the best accuracy to predict mortality in leptospirosis [area under the curve (AUC-ROC) = 0.776]. A score-based prediction was carried out with the coefficients of this model and named LeptoScore. Then, to simplify the predictive tool, a new score was built by attributing points to the predictors with importance values higher than 1. The simplified score, named QuickLepto, has five variables (age > 40 years; lethargy; pulmonary symptom; mean arterial pressure < 80 mmHg and hematocrit < 30%) and good predictive accuracy (AUC-ROC = 0.788). LeptoScore and QuickLepto had better accuracy to predict mortality in patients with leptospirosis when compared to SPIRO score (AUC-ROC = 0.500) and quick SOFA score (AUC-ROC = 0.782). The main result is a new scoring system, the QuickLepto, that is a simple and useful tool to predict death in leptospirosis patients at hospital admission.
Assuntos
Leptospirose , Humanos , Adulto , Curva ROC , Leptospirose/diagnóstico , Fatores de Risco , Hematócrito , Aprendizado de Máquina , Estudos RetrospectivosRESUMO
Introduction: The 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. Methods: Multicenter 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. Results: The 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 64â ml/min/1.73â 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 46â ml/min/1.73â 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 36â ml/min/1.73â 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. Discussion: The 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.
Assuntos
COVID-19 , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , SARS-CoV-2 , TransplantadosRESUMO
BACKGROUND: The chronic use of immunosuppressive drugs is a key risk factor of death because of coronavirus disease 2019 (COVID-19) in kidney transplant recipients (KTRs), although no evident association between the class of immunosuppressive and outcomes has been observed. Thus, we aimed to compare COVID-19-associated outcomes among KTRs receiving 3 different immunosuppressive maintenance regimes. METHODS: This study included data from 1833 KTRs with COVID-19 diagnosed between March 20 and April 21 extracted from the national registry before immunization. All patients were taking calcineurin inhibitor associated with mycophenolate acid (MPA, n = 1258), azathioprine (AZA, n = 389), or mammalian targets of rapamycin inhibitors (mTORi, n = 186). Outcomes within 30 and 90 d were assessed. RESULTS: Compared with patients receiving MPA, the 30-d (79.9% versus 87.9% versus 89.2%; P < 0.0001) and 90-d (75% versus 83.5% versus 88.2%; P < 0.0001) unadjusted patient survivals were higher in those receiving AZA or mTORi, respectively. Using adjusted multivariable Cox regression, compared with patients receiving AZA, the use of MPA was associated with a higher risk of death within 30 d (adjusted hazard ratio [aHR], 1.70; 95% confidence interval [CI], 1.21-2.40; P = 0.003), which was not observed in patients using mTORi (aHR, 0.78; 95% CI, 0.45-1.35; P = 0.365). At 90 d, although higher risk of death was confirmed in patients receiving MPA (aHR, 1.46; 95% CI, 1.09-1.98; P = 0.013), a reduced risk was observed in patients receiving mTORi (aHR, 0.59; 95% CI, 0.35-0.97; P = 0.04) compared with AZA. CONCLUSIONS: This national cohort data suggest that, in KTRs receiving calcineurin inhibitor and diagnosed with COVID-19, the use of MPA was associated with higher risk of death, whereas mTORi use was associated with lower risk of death.
Assuntos
COVID-19 , Transplante de Rim , Azatioprina , Inibidores de Calcineurina/efeitos adversos , Inibidores Enzimáticos , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Ácido Micofenólico/efeitos adversos , Sirolimo/efeitos adversos , Serina-Treonina Quinases TORRESUMO
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
BACKGROUND AND OBJECTIVES: Patients undergoing kidney replacement therapies (KRTs) have a poor prognosis after Covid-19 infection. Few studies have compared the outcomes of such patients in the different KRT modalities. This study aimed to analyze the 30-day Covid-19-associated case-fatality rate of dialysis and kidney transplant patients. METHODS: Retrospective cohort study analyzing data from patients with confirmed Covid-19 between Mar/20 and Jan/21 included in two multicenter studies, the Brazilian Covid-19 Dialysis Study (Dialysis group, n = 703) and the Covid-19-KT Brazilian Study (Transplant group, n = 1907). To assess the risk factors for death, adjusted Cox hazards models were used. A sensitivity analysis was performed using a propensity score analysis to match the groups (n = 587 patients in each group). RESULTS: A higher percentage of transplant patients required hospitalization (68 vs. 51%, p < 0.001), intensive care (37 vs. 30%, p = 0.023), and invasive mechanical ventilation (28 vs. 22%, p = 0.035). Multivariate analysis of the before-matching sample showed that subjects in the transplant group were at a lower death risk at baseline (HR 0.380.560.85). However, they showed higher risk over time (HR 1.031.061.09). Kaplan-Meier analysis after propensity score matching confirmed the inferior 30-day cumulative survival in the transplant recipients (83 vs. 78%, p = 0.0014). CONCLUSION: Both transplant and dialysis patients have high 30-day case-fatality rates after a Covid-19 diagnosis. Despite lower death risk at baseline, transplant patients have an increased death risk of 6% per day than dialysis patients.
Assuntos
Teste para COVID-19 , COVID-19 , Estudos de Coortes , Humanos , Pontuação de Propensão , Diálise Renal/efeitos adversos , Estudos Retrospectivos , SARS-CoV-2RESUMO
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.
Assuntos
COVID-19 , Transplante de Rim , Teste para COVID-19 , Humanos , Internet , Transplante de Rim/efeitos adversos , Curva ROC , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , TransplantadosRESUMO
Reports on tropical infections among kidney transplant (KT) recipients have increased in recent years, mainly because of the growing number of KT programs located in tropical and subtropical areas, and greater mobility or migration between different areas of the world. Endemic in emerging and developing regions, like most countries in Latin America, tropical infections are an important cause of morbidity and mortality in this population. Tropical infections in KT recipients may exhibit different pathways for acquisition compared with those in nonrecipients, such as transmission through a graft and reactivation of a latent infection triggered by immunosuppression. Clinical presentation may differ compared with that in immunocompetent patients, and there are also particularities in diagnostic aspects, treatment, and prognosis. KT patients must be screened for latent infections and immunized properly. Last, drug-drug interactions between immunosuppressive agents and drugs used to treat tropical infections are an additional challenge in KT patients. In this review, we summarize the management of tropical infections in KT patients.
Assuntos
Infecções por Arbovirus/diagnóstico , Doença de Chagas/diagnóstico , Transplante de Rim , Leishmaniose/diagnóstico , Estrongiloidíase/diagnóstico , Tuberculose/diagnóstico , Infecções por Arbovirus/imunologia , Infecções por Arbovirus/terapia , Doença de Chagas/imunologia , Doença de Chagas/terapia , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/imunologia , Febre de Chikungunya/terapia , Dengue/diagnóstico , Dengue/imunologia , Dengue/terapia , Rejeição de Enxerto/prevenção & controle , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , América Latina , Leishmaniose/imunologia , Leishmaniose/terapia , Estrongiloidíase/imunologia , Estrongiloidíase/terapia , Tuberculose/imunologia , Tuberculose/terapia , Febre Amarela/diagnóstico , Febre Amarela/imunologia , Febre Amarela/terapia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/imunologia , Infecção por Zika virus/terapiaRESUMO
This retrospective multicenter (n = 18) cohort study evaluated the incidence, risk factors, and the impact of delayed graft function (DGF) on 1-year kidney transplant (KT) outcomes. Of 3992 deceased donor KT performed in 2014-2015, the incidence of DGF was 54%, ranging from 29.9% to 87.7% among centers. Risk factors (lower-bound-95%CI OR upper-bound-95%CI ) were male gender (1.066 1.2491.463 ), diabetic kidney disease (1.053 1.2961.595 ), time on dialysis (1.005 1.0071.009 ), retransplantation (1.035 1.3971.885 ), preformed anti-HLA antibodies (1.011 1.3831.892 ), HLA mismatches (1.006 1.0661.130 ), donor age (1.011 1.0171.023 ), donor final serum creatinine (sCr) (1.239 1.3171.399 ), cold ischemia time (CIT) (1.031 1.0431.056 ), machine perfusion (0.401 0.5420.733 ), and induction therapy with rabbit antithymocyte globulin (rATG) (0.658 0.8000.973 ). Duration of DGF > 4 days was associated with inferior renal function and DGF > 14 days with the higher incidences of acute rejection, graft loss, and death. In conclusion, the incidence and duration of DGF were high and associated with inferior graft outcomes. While late referral and poor donor maintenance account for the high overall incidence of DGF, variability in donor and recipient selection, organ preservation method, and type of induction agent may account for the wide variation observed among transplant centers.
Assuntos
Transplante de Rim , Brasil/epidemiologia , Estudos de Coortes , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Estudos Retrospectivos , Fatores de Risco , Doadores de TecidosRESUMO
BACKGROUND: There are only a few reports evaluating the applicability of endothelial-damage markers analysis by immunohistochemistry (IHC) in kidney allograft samples. This study analyzed the expression of Caveolin-1 (Cav), von Willebrand factor (Vwf), and T-cadherin (Cad) in kidney biopsies and their association with antibody-mediated injury. METHODS: In this retrospective study, 114 cases with antibody-mediated changes (Banff, 2020) and 72 with interstitial fibrosis/tubular atrophy were selected. IHC for Cav, Vwf and Cad was performed and evaluated according to their qualitative expression in peritubular capillaries. The cases were grouped according to the presence of microvascular inflammation (MVI), donor-specific antibodies (DSA), C4d positivity and antibody-mediated rejection (AMR). A level of significance < 0.05 was adopted. RESULTS: Vwf expression was associated with MVI (p < 0.001), DSA (p = 0.016), C4d (p < 0.001) and AMR (p < 0.001), and was higher in DSA+/C4d+ cases despite MVI (p < 0.001). The expression of Cad correlated with MVI (p = 0.015), C4d (p = 0.005) and AMR (p = < 0.001). Cad was more expressed in chronic AMR compared with acute/active cases (p = 0.001). Cav expression was associated with MVI (p = 0.029) and AMR (p = 0.016) and was also higher in chronic AMR (p = 0.049). A combined score of Vwf and Cad was higher in AMR when compared with C4d without rejection and IF/TA cases (p < 0.001). CONCLUSION: Vwf, Cad and Cav expression shows association with antibody-mediated injury and may be helpful to support AMR diagnosis.