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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.

Abstract Background The measurement of native T1 through cardiovascular magnetic resonance (CMR) is a noninvasive method of assessing myocardial fibrosis without gadolinium contrast. No studies so far have evaluated native T1 after renal transplantation. The primary aim of the current study is to assess changes in the myocardium native T1 6 months after renal transplantation. Methods We prospectively evaluated 44 renal transplant patients with 3 T CMR exams: baseline at the beginning of transplantation and at 6 months after transplantation. Results The native T1 time was measured in the midventricular septum and decreased significantly from 1331 ± 52 ms at the baseline to 1298 ± 42 ms 6 months after transplantation (p = 0.001). The patients were split into two groups through a two-step cluster algorithm: In cluster-1 (n = 30) the left ventricular (LV) mass index and the prevalence of diabetes were lower. In cluster-2 (n = 14) the LV mass index and diabetes prevalence were higher. Decrease in native T1 values was significant only in the patients in cluster-1 (p = 0.001). Conclusions The native myocardial T1 time decreased significantly 6 months after renal transplant, which may be associated with the regression of the reactive fibrosis. The patients with greater baseline LV mass index and the diabetic group did not reach a significant decrease in T1.

Background Atypical Hemolytic Uremic Syndrome (aHUS) is an ultra-rare disease that potentially leads to kidney graft failure due to ongoing Thrombotic Microangiopathy (TMA). The aim was evaluating the frequency of TMA after kidney transplantation in patients with aHUS in a Brazilian cohort stratified by the use of the specific complement-inhibitor eculizumab. Methods This was a multicenter retrospective cohort study including kidney transplant patients diagnosed with aHUS. We collected data from 118 transplant centers in Brazil concerning aHUS transplanted patients between 01/01/2007 and 12/31/2019. Patients were stratified into three groups: no use of eculizumab (No Eculizumab Group), use of eculizumab for treatment of after transplantation TMA (Therapeutic Group), and use of eculizumab for prophylaxis of aHUS recurrence (Prophylactic Group). Results Thirty-eight patients with aHUS who received kidney transplantation were enrolled in the study. Patients’ mean age was 30 years (24–40), and the majority of participants was women (63% of cases). In the No Eculizumab Group (n = 11), there was a 91% graft loss due to the TMA. The hazard ratio of TMA graft loss was 0.07 [0.01–0.55], p = 0.012 in the eculizumab Prophylactic Group and 0.04 [0.00–0.28], p = 0.002 in the eculizumab Therapeutic Group. Conclusion The TMA graft loss in the absence of a specific complement-inhibitor was higher among the Brazilian cohort of kidney transplant patients. This finding reinforces the need of eculizumab use for treatment of aHUS kidney transplant patients. Cost optimization analysis and the early access to C5 inhibitors are suggested, especially in low-medium income countries.

BackgroundPredicting waiting time for a deceased donor kidney transplant can help patients and clinicians to discuss management and contribute to a more efficient use of resources. This study aimed at developing a predictor model to estimate time on a kidney transplant waiting list using a machine learning approach.MethodsA retrospective cohort study including data of patients registered, between January 1, 2000 and December 31, 2017, in the waiting list of São Paulo State Organ Allocation System (SP-OAS) /Brazil. Data were randomly divided into two groups: 75% for training and 25% for testing. A Cox regression model was fitted with deceased donor transplant as the outcome. Sensitivity analyses were performed using different Cox models. Cox hazard ratios were used to develop the risk-prediction equations.ResultsOf 54,055 records retrieved, 48,153 registries were included in the final analysis. During the study period, approximately 1/3 of the patients were transplanted with a deceased donor. The major characteristics associated with changes in the likelihood of transplantation were age, subregion, cPRA, and frequency of HLA-DR, -B and -A. The model developed was able to predict waiting time with good agreement in internal validation (c-index = 0.70).ConclusionThe kidney transplant waiting time calculator developed shows good predictive performance and provides information that may be valuable in assisting candidates and their providers. Moreover, it can significantly improve the use of economic resources and the management of patient care before transplant.

ABSTRACT Introduction: The progress in kidney transplantation has been evident over the years, as well as its benefits for patients. Objectives: To evaluate the 1.000 kidney transplants performed at the Botucatu Medical School University Hospital, subdividing the patients in different periods, according to the current immunosuppression, and evaluating the differences in graft and patient survival. Methods: Retrospective cohort analysis of the transplants performed between 06/17/87 to 07/31/16, totaling 1,046 transplants, subdivided into four different periods: 1) 1987 to 2000: cyclosporine with azathioprine; 2) 2001 to 2006: cyclosporine with mycophenolate; 3) 2007 to 2014: tacrolimus with antimetabolic; and 4) 2015 to 2016: tacrolimus with antimetabolic, with increased use of the combination of tacrolimus and mTOR inhibitors. Results: There was an increase in the mean age of recipients and increase in deceased donors and their age in the last two periods. There was a reduction in graft function delay, being 54.3% in the fourth period, compared to 78.8% in the first, p = 0.002. We found a reduction in acute rejection, being 6.1% in the last period compared to 36.3% in the first, p = 0.001. Urological complications and diabetes after transplantation were more frequent in the first two periods. The rates of cytomegalovirus infection were higher in the last two periods. There was an improvement in graft survival, p = 0.003. There was no difference in patient survival, p = 0.77 (Figure 2). Conclusion: There was a significant increase in the number of transplants, with evolution in graft survival, despite the worsening in the profiles of recipients and donors.

Resumo Introdução: A indicação de terapia de indução não é consensual em doadores vivos. Objetivo: Comparar não indução com indução com basiliximab e timoglobulina na incidência de rejeição aguda em transplante renal com doador vivo. Métodos: Todos os casos de transplante renal com doador vivo realizados no serviço de transplante do Hospital das Clínicas de Botucatu da UNESP no período de janeiro de 2010 a dezembro de 2013. O grupo foi dividido pelo tipo de medicação usada na indução. Resultados: Foram avaliados 90 pacientes. Não houve diferenças nas características basais de idade e doença de base. A taxa de rejeição aguda comprovada por biópsia foi maior no grupo sem indução (42,9%) em comparação aos grupos basiliximab (20%) e timoglobulina (16,7%), p = 0,04. A divisão das rejeições por compatibilidade mostra que os idênticos apresentaram menor taxa de rejeição (10%). O grupo haploidêntico sem indução apresentou as maiores taxas de rejeição (53,3%). No grupo distinto, todos foram induzidos e as taxas de rejeição foram semelhantes com basiliximab ou timoglobulina, p = NS. O uso de terapia de indução associou-se de forma independente a menor risco de rejeição (OR = 0,32 IC: 0,11-0,93, p = 0,036). Não houve diferenças na função renal aos 6 meses e sobrevida do paciente e enxerto nos três grupos. Discussão: Os pacientes haploidênticos sem indução foram os que apresentaram maiores taxas de rejeição aguda. O grupo de pacientes induzidos com timoglobulina apresentava maior risco imunológico, entretanto, eles mostraram baixas taxas de rejeição. Conclusão: O uso de terapia de indução resultou em menores taxas de rejeição em transplante com doador vivo.

The treatment of choice for Atypical Hemolytic Uremic Syndrome (aHUS) is the monoclonal antibody eculizumab. The objective of this study was to assess the efficacy and safety of eculizumab in a cohort of kidney transplant patients suffering from aHUS.Description of the prospective cohort of all the patients primarily treated with eculizumab after transplantation and divided into the therapeutic (onset of aHUS after transplantation) and prophylactic use (patients with previous diagnosis of aHUS undergoing kidney transplantation).Seven cases were outlined: five of therapeutic use and two, prophylactic. From the five cases of therapeutic use, there was improvement of the thrombotic microangiopathy in the 48 hours following the start of the drug and no patient experienced relapse during an average follow-up of 21 months in the continuous use of eculizumab (minimum of 6 and maximum of 42 months). One patient died at 6 months, due to Aspergillus infection. From the two cases of prophylactic use, one patient experienced relapsed thrombotic microangiopathy after 4 months and another patient remained asymptomatic after 16 months of follow-up, both on chronic treatment.The therapeutic use of eculizumab showed to be effective, with improvement of the microangiopathy parameters and persisting up to the end of the follow-up, without relapses. The additional risk of immunosuppression, leading to opportunistic infections, was well tolerated. The prophylactic use showed to be effective and safe; however, the doses and intervals should be individualized in order to avoid relapsed microangiopathy, especially in patients with factor H mutation.

Several grain sizes were obtained by heat treatment at different temperatures for interstitial-free (IF) and 2.25Cr-1Mo steels. Samples of the steels with different grain sizes were aged at 600 and 680 °C for IF steel and 520 and 560 °C for 2.25Cr-1Mo steel for sufficient time to achieve their equilibrium grain boundary segregation. The grain boundary concentrations of phosphorus were examined using Auger electron spectroscopy. At the same aging temperature, the boundary segregation of phosphorus increased with increasing grain size. The effect of grain size on equilibrium grain boundary segregation thermodynamics was analyzed based on the information of both grain size and phosphorus boundary concentration. The segregation enthalpy increased with increasing grain size and simultaneously the segregation entropy became less negative. Moreover, the segregation entropy (∆S) and enthalpy (∆H) of phosphorus in both IF and 2.25Cr-1Mo steels exhibited a unified linear relationship, being expressed as ∆S = 0.85∆H − 38.06, although it segregated to different types of grain boundaries (ferrite grain boundaries in IF steel and prior austenite grain boundaries in 2.25Cr-1Mo steel). With the aid of the acquired thermodynamic parameters and grain boundary segregation theories, the equilibrium segregation concentrations at different aging temperatures were modeled under different grain sizes for both steels.

The lack of discharge observations and reliable drainage information is a pervasive problem in urban catchments, resulting in difficulties in parameterizing urban hydrological models. Current parameterization methods for ungauged urban catchments mostly rely on subjective experiences or simplified models, resulting in inadequate accuracy for urban flood prediction. Parameter regionalization has been widely used to tackle model parameterization issues, but has rarely been employed for urban hydrological models. How to conduct effective parameter regionalization for urban hydrological models remains to be investigated. Here we propose a parameter regionalization framework (PRF) that integrates donor catchment clustering and the optimal regression‐based methods in each cluster. The PRF is applied to an urban hydrological model, the Time Variant Gain Model in urban areas (TVGM_Urban), in 37 urban catchments in Shenzhen City, China. We first show satisfactory flood simulation performance of TVGM_Urban for all urban catchments. Subsequently, we employ the PRF for parameter regionalization of TVGM_Urban. PRF classifies 37 urban catchments into three groups, and the partial least‐squares regression is identified as optimal regression‐based method for Groups 1 and 2, while the random forest model is found to be best for Group 3. To evaluate the simulation performance of PRF, we compare it with eight single regionalization methods. The results indicate better simulation performance and lower uncertainty of PRF, and donor catchment clustering can effectively enhance the simulation performance of linear regression‐based methods. Lastly, we identify curve number, land cover area ratios, and slope as critical factors for most TVGM_Urban parameters based on PRF results. Plain Language Summary: Frequent urban flooding and waterlogging pose significant threats to human life and property. Accurate modeling urban floods is crucial for minimizing damages caused by urban flooding. However, the delayed initiation of urban observations has resulted in prevalent data scarcity in urban areas, leading to difficulties and low accuracy in estimating model parameters for ungauged urban catchments. This study proposes a parameter regionalization framework for an urban hydrological model to improve the accuracy of flood simulations in ungauged urban catchments. This framework involves classifying gauged catchments into multiple groups and identifying the optimal regression‐based methods in each group for parameter regionalization. The flood simulation performance and stability of the parameter regionalization framework is evaluated by comparing it with eight widely‐used regionalization methods in 37 urban catchments located in Shenzhen City, China. Our results show that the classification of gauged catchments can significantly improve the simulation performance of linear regression methods. Additionally, the parameter regionalization framework outperforms the other regionalization methods for both urban flood simulation in the study area and urban flood prediction in the ungauged urban catchments. This study provides a novel and efficient parameterization method for accurate flood prediction in ungauged urban catchments to reduce potential losses. Key Points: TVGM_Urban presents satisfying performance in urban flood modelingThe PRF integrating donor catchment clustering and optimal regression methods in each cluster outperforms single regionalization methodsCurve number, land cover area ratio, and slope are critical factors for runoff generation parameters of TVGM_Urban [ABSTRACT FROM AUTHOR]

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.