Eculizumab in low-middle income countries: how much does a life cost?

Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare disease and eculizumab was approved as first line therapy in 2011 by the Food and Drug Administration. Access to eculizumab in low-middle income countries is challenging. We discuss access to eculizumab in Brazil that was made possible by judicialization or compassionate use. We showed a nationwide cohort of unplanned eculizumab interruptions resulted in higher rates of aHUS relapse. Similar to the French cohort, the use of eculizumab after transplantation showed superior graft survival compared to conventional treatment. We speculate a possible solution to the higher cost of eculizumab in which the government negotiates with the manufacturers. In this process, the government should compromise to ensure validated protocols of drug use, and the pharmaceutical companies, on the other hand, should reduce prices, especially in low-income countries. We also suggest a price adjustment based on gross domestic product.

Thrombotic microangiopathy after kidney transplantation: Analysis of the Brazilian Atypical Hemolytic Uremic Syndrome cohort.

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.

A machine learning prediction model for waiting time to kidney transplant.

BACKGROUND: Predicting 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. METHODS: A 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. RESULTS: Of 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). CONCLUSION: The 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.

Exploring the causes of the high incidence of delayed graft function after kidney transplantation in Brazil: a multicenter study.

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.

Eculizumab interruption in atypical hemolytic uremic syndrome due to shortage: analysis of a Brazilian cohort.

BACKGROUND: The risk of eculizumab therapy discontinuation in patients with atypical hemolytic uremic syndrome (aHUS) is unclear. The main objective of this study was to analyze the risk of aHUS relapse after eculizumab interruption due to drug shortage in Brazil. METHODS: We screened all the registered dialysis centers in Brazil (n = 800), willing to participate in the aHUS Brazilian shortage cohort, through electronic mail and formal invitation by the Brazilian Society of Nephrology. We included patients with aHUS whose eculizumab therapy underwent unplanned discontinuation for at least 30 days between January 1st, 2016 and December 31st, 2019 during the maintenance phase of treatment. Relapse was defined by the development of thrombocytopenia, hemolytic anemia, acute kidney injury or thrombotic microangiopathy (TMA) in a kidney biopsy. RESULTS: We analyzed 25 episodes of exposure to risk of relapse, from 24 patients. Median age was 33 (6-53) years, 18 (72%) were female, 9 (36%) had a functioning renal graft, 5 (20%) were undergoing dialysis. CFH variant was found in 8 (32%) episodes. There were 11 relapses. The risk of relapse was 34%, 44.5% and 58% at 114, 150 and 397 days, respectively. No baseline variable was related to relapse in Cox multivariate analysis, including CFH variant. CONCLUSIONS: In this study, the cumulative incidence of aHUS relapse at 397 days was 58% after eculizumab interruption. The presence of complement variant does not seem to be associated with a higher relapse rate. The eculizumab interruption was deemed not safe, considering that the rate of relapse was high.

Kidney transplantation with donors in severe acute kidney injury. Should we use these organs? Retrospective Case Series / Transplante renal com doadores em lesão renal aguda severa. Devemos utilizar esses órgãos? Série de casos retrospectiva

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.

RESUMO Introdução: O número de pacientes incidentes e prevalentes em diálise tem aumentado, assim como o número de candidatos ao transplante renal no Brasil, sem um aumento proporcional do número de doadores de órgãos. O uso de rins expandidos, quanto à função renal, pode ser uma alternativa para aumentar a oferta de órgãos. Objetivo: discutir a viabilidade do uso de rins expandidos quanto à função renal, que estejam em lesão renal aguda severa. Métodos: foram avaliados todos os casos de transplante renal de doador falecido realizados no Hospital das Clínicas de Botucatu da UNESP, de janeiro de 2010 a junho de 2018, totalizando 732 casos. Selecionou-se os casos com creatinina final do doador maior do que 6 mg/dL. Resultados: quatro pacientes foram selecionados, dos quais todos os doadores estavam em lesão renal aguda (LRA) severa. Esses doadores apresentavam rabdomiólise como provável causa de LRA severa, eram jovens, sem comorbidades e apresentavam diminuição de volume urinário nas últimas 24 horas. A evolução clínica de todos os receptores foi satisfatória, com taxa de filtração glomerular após o transplante variando entre 48 a 98 mL/min/1,73m2. Conclusão: essa série de casos mostra a possibilidade de utilização de doadores renais em LRA severa, desde que respeitadas as condições seguintes: idade do doador, rabdomiólise como causa de LRA e achados de biópsia favoráveis à implantação. Estudos adicionais com melhores desenhos, maior número de pacientes e maiores tempos de seguimento são necessários.

Kidney transplantation with donors in severe acute kidney injury. Should we use these organs? Retrospective Case Series.

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.

Kidney transplantation is associated with reduced myocardial fibrosis. A cardiovascular magnetic resonance study with native T1 mapping.

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.

Evaluation of the 1000 renal transplants carried out at the University Hospital of the Botucatu Medical School (HCFMB) - UNESP and their evolution over the years.

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.

Evaluation of the 1000 renal transplants carried out at the University Hospital of the Botucatu Medical School (HCFMB) - UNESP and their evolution over the years / Avaliação dos 1000 transplantes renais realizados no Hospital das Clínicas da Faculdade de Medicina de Botucatu (HCFMB) da UNESP e a sua evolução ao longo dos anos

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: O progresso no transplante renal tem sido evidente ao longo dos anos, assim como seus benefícios para os pacientes. Objetivos: Avaliar os 1000 transplantes renais realizados no Hospital das Clínicas da Faculdade de Medicina de Botucatu, subdividindo os pacientes em diferentes períodos, de acordo com a imunossupressão vigente, e avaliar as diferenças em relação à sobrevida do enxerto e do paciente. Métodos: Análise da coorte retrospectiva dos transplantes realizados entre 17/06/87 a 31/07/16, totalizando 1046 transplantes, subdivididos em quatro diferentes períodos: 1) 1987 a 2000: ciclosporina com azatioprina; 2) 2001 a 2006: ciclosporina com micofenolato; 3) 2007 a 2014: tacrolimo com antimetabólico; e 4) 2015 a 2016: tacrolimo com antimetabólico, com aumento do uso da combinação de tacrolimo com inibidores da mTOR. Resultados: Houve aumento da idade média dos receptores e aumento de doadores falecidos e da idade destes nos dois últimos períodos. Observou-se redução de retardo de função do enxerto, sendo de 54,3% no quarto período, em comparação a 78,8% no primeiro, p = 0,002. Observamos redução de rejeição aguda, sendo 6,1% no último período em comparação a 36,3% no primeiro, p = 0,001. As complicações urológicas e o diabetes após o transplante foram mais frequentes nos primeiros dois períodos. As taxas de infecção por citomegalovírus foram maiores nos dois últimos períodos. Houve melhoria na sobrevida do enxerto, p = 0,003. Não houve diferença na sobrevida do paciente, p = 0,77 (Figura 2). Conclusão: Houve aumento significativo no número de transplantes, com evolução na sobrevida do enxerto, apesar da piora no perfil dos receptores e doadores.

Nephrectomy Versus Embolization of Non-Functioning Renal Graft: A Systematic Review with a Proportional Meta-Analysis.

There is no standardization on the timing of the best approach to treat a non-functioning renal graft. We reviewed the literature and performed a proportional meta-analysis of case series of transplantectomy and embolization for a non-functioning renal graft. The groups were compared for mortality and morbidity outcomes. A total of 2421 patients were included in this review. Of these, 2232 patients underwent transplantectomy and 189 underwent percutaneous embolization. The mortality rate in the nephrectomy group was 4% [95% confidence interval [CI], 2-7%; I²=87%] as compared with 0.1% [95% CI, 0.1-0.5%; I²=0%] in the embolization group. The rates of common morbidities were 18% [95% CI, 13-26%, I²=79.7%] for nephrectomy compared with 1.2% [95% CI, 0.7-2.1%, I²=26.4%] for embolization. The incidence of post-embolization syndrome was 68%, and 20% of patients needed post-embolization nephrectomy. Percutaneous embolization was associated with lower mortality and morbidity rates but also with a high rate of post-embolization syndrome. However, in most cases this complication had easily manageable symptoms. Embolization is a new and attractive technique that can be considered in treating non-functioning renal grafts.

Sirolimus Associated with Tacrolimus at Low Doses in Elderly Kidney Transplant Patients: A Prospective Randomized Controlled Trial.

OBJECTIVES: There is no consensus on the best immunosuppressive regimen for elderly renal transplant recipients. The objective of this study was to assess cytomegalovirus infection incidence and kidney transplant outcomes in elderly recipients treated with mammalian target of rapamycin inhibitors sirolimus/ tacrolimus at low doses compared with those receiving tacrolimus/mycophenolate sodium. MATERIALS AND METHODS: In this single-center prospective randomized study (Trial Registration No. NCT02683291), kidney transplant recipients over 60 years of age were randomly allocated into 2 groups: tacrolimus-sirolimus (21 patients) and tacrolimus-mycophenolate (23 patients). Cytomegalovirus infection rate and patient survival, biopsy-proven acute rejection, and renal function at 12 months were assessed. RESULTS: Cytomegalovirus infection rate was higher in the mycophenolate group (60.9%) than in the sirolimus group (16.7%; P = .004). The rates of biopsy-proven acute rejection, patient survival, graft survival, and estimated glomerular filtration rate over 12 months did not significantly differ between groups. CONCLUSIONS: The incidence of cytomegalovirus infection was significantly lower in the sirolimus group. The use of tacrolimus combined with sirolimus in elderly kidney transplant recipients is safe.

Long-term outcomes of the Atypical Hemolytic Uremic Syndrome after kidney transplantation treated with eculizumab as first choice.

INTRODUCTION: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.

A case report of venous thrombosis after kidney transplantation - We can save the graft? Time is the success factor.

INTRODUCTION: Venous thrombosis is a serious surgical complication that frequently results in loss of kidney graft. CASE PRESENTATION: We report the case of a female patient recipient of a decease kidney transplant that in the tenth postoperative presented with hematuria, graft pain and oliguria. Ultrasound examination was suggestive of venous thrombosis with abnormal doppler waveform pattern and reversal of diastolic flow. She underwent emergency surgical intervention after 2h of diagnosis. The vein thrombus was removed by perfusing the renal graft artery with 1000ml of Euro-Collins solution. The patient evolves with recovery of renal function after 1 week of the procedure DISCUSSION: Similar reports of graft rescue in the vein thrombosis are scarce and that the time of diagnosis to intervention is a determining factor. CONCLUSION: Rapid diagnosis of exactly 2h combined with the early re-operation may be successful in preserving renal graft in cases of venous thrombosis.

Behavioral measures to reduce non-adherence in renal transplant recipients: a prospective randomized controlled trial.

PURPOSE: Solid-organ transplant recipients present a high rate of non-adherence to drug treatment. Few interventional studies have included approaches aimed at increasing adherence. The objective of this study was to evaluate the impact of an educational and behavioral strategy on treatment adherence of kidney transplant recipients. METHODS: In a randomized prospective study, incident renal transplant patients (n = 111) were divided into two groups: control group (received usual transplant patient education) and treatment group (usual transplant patient education plus ten additional weekly 30-min education/counseling sessions about immunosuppressive drugs and behavioral changes). Treatment adherence was assessed using ITAS adherence questionnaire after 3 months. Renal function at 3, 6, and 12 months, and the incidence of transplant rejection were evaluated. RESULTS: The non-adherence rates were 46.4 and 14.5 % in the control and treatment groups (p = 0.001), respectively. The relative risk for non-adherence was 2.59 times (CI 1.38-4.88) higher in the control group. Multivariate analysis demonstrated a 5.84 times (CI 1.8-18.8, p = 0.003) higher risk of non-adherence in the control group. There were no differences in renal function and rejection rates between groups. CONCLUSIONS: A behavioral and educational strategy addressing the patient's perceptions and knowledge about the anti-rejection drugs significantly improved the short-term adherence to immunosuppressive therapy.

Sepsis and AKI in Clinical Emergency Room Patients: The Role of Urinary NGAL.

BACKGROUND: Few studies have investigated the predictive properties of urinary (u) NGAL as an AKI marker in septic population. OBJECTIVES: This study evaluated the efficacy of uNGAL as predictor of AKI and death in septic patients admitted to the clinical emergency room (ER). METHODOLOGY: We prospectively studied patients with sepsis admitted to the ER. Urine was analyzed for NGAL within the first 24 hours after admission (classified as NGAL1), between 24 and 48 h (NGAL2), and at moment of AKI diagnosis (NGAL3). RESULTS: Among 168 septic patients admitted to ER, 72% developed AKI. The uNGAL and its relationship with creatinine (Cr) were high in septic patients but statistically higher in those with sepsis and AKI. The uNGAL1 and uNGAL2, as well as uNGAL1/uCr1 and uNGAL2/uCr2, were good predictors for AKI (AUC-ROC 0.73, 0.70, 0.77, and 0.84, resp.). The uNGAL1 and uNGAL1/uCr1 were poor predictors for death (AUC-ROC 0.66 and 0.68, resp.), whereas uNGAL2 and uNGAL2/uCr2 were better predictors (AUC-ROC 0.70 and 0.81, resp.). CONCLUSION: The uNGAL is highly sensitive but nonspecific predictor of AKI and death in septic patients admitted into ER.

Different induction therapies for kidney transplantation with living donor.

INTRODUCTION: Indications for induction therapy is not consensual in living donors. OBJECTIVE: The objective of this study was compare no induction with thymoglobulin and basiliximab induction in the incidence of acute rejection in kidney transplantation with living donor. METHODS: We select all cases of renal transplantation with living donor performed in Hospital das Clínicas de Botucatu da UNESP during the period of January 2010 to December 2013. The group was divided by the type of medication used for induction. RESULTS: A total of 90 patients were evaluated. There were no differences in baseline characteristics of age and underlying disease. The rate of biopsy-proven acute rejection was higher in the group without induction (42.9%) compared to basiliximab group (20%) and Thymoglobulin (16.7%), p = 0.04. The rejection by compatibility shows that the identical had the lower rejection rate (10%). The haploidentical group without induction had the highest rejection rates (53.3%). In all distinct group the rejection rates were similar with basiliximab or Thymoglobulin, p = NS. The use of induction therapy was associated independently with a lower risk of rejection (OR = 0.32 CI: 0.11 to 0.93, p = 0.036). There were no differences in renal function at 6 months and patient survival and graft in the three groups. DISCUSSION: The haploidentical patients without induction were those with higher rates of acute rejection. The group of patients induced with Thymoglobulin had a higher immunological risk, however showed low rates of rejection. CONCLUSION: The use of induction therapy resulted in lower rates of rejection in transplantation with living donor.

Diferentes esquemas de indução para transplante renal com doador vivo / Different induction therapies for kidney transplantation with living donor

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. .

Abstract Introduction: Indications for induction therapy is not consensual in living donors. Objective: The objective of this study was compare no induction with thymoglobulin and basiliximab induction in the incidence of acute rejection in kidney transplantation with living donor. Methods: We select all cases of renal transplantation with living donor performed in Hospital das Clínicas de Botucatu da UNESP during the period of January 2010 to December 2013. The group was divided by the type of medication used for induction. Results: A total of 90 patients were evaluated. There were no differences in baseline characteristics of age and underlying disease. The rate of biopsy-proven acute rejection was higher in the group without induction (42.9%) compared to basiliximab group (20%) and Thymoglobulin (16.7%), p = 0.04. The rejection by compatibility shows that the identical had the lower rejection rate (10%). The haploidentical group without induction had the highest rejection rates (53.3%). In all distinct group the rejection rates were similar with basiliximab or Thymoglobulin, p = NS. The use of induction therapy was associated independently with a lower risk of rejection (OR = 0.32 CI: 0.11 to 0.93, p = 0.036). There were no differences in renal function at 6 months and patient survival and graft in the three groups. Discussion: The haploidentical patients without induction were those with higher rates of acute rejection. The group of patients induced with Thymoglobulin had a higher immunological risk, however showed low rates of rejection. Conclusion: The use of induction therapy resulted in lower rates of rejection in transplantation with living donor. .

Acute kidney injury in septic patients admitted to emergency clinical room: risk factors and outcome.

PURPOSE: Acute kidney injury (AKI) is a common source of morbidity in sepsis. We sought to determine risk factors for AKI, by acute kidney injury network (AKIN) criteria, in septic patients admitted in emergency clinical room (ER). MATERIALS AND METHODS: Prospective cohort study of 200 patients admitted to the ER of a University Hospital, followed for development of AKI over 5 days. RESULTS: AKI developed in 144/200 (72 %) patients. In multivariable regression analysis, independent risk factors for AKI included age over 65 years (OR 1.28; 95 % CI 1.12-1.89; p = 0.04), mean blood pressure (MBP) lower than 65 mmHg at moment of admission (OR 1.89; 95 % CI 1.43-2.64, p = 0.003) and diabetes mellitus (OR 1.66; 95 % CI 1.30-3.20; p = 0.012). Mortality rate was 51.4 % in AKI patients compared with 26.8 % for those without AKI (p = 0.002). Septic shock (OR = 1.83, 95 % CI 1.23-2.74, p = 0.007), AKIN 3 (OR = 1.64; 95 % CI 1.19-1.89, p = 0.02), APACHE 2 > 20 (OR 1.92, 95 % CI 1.34-2.02, p = 0.009) and need for dialysis (OR = 1.26, 95 % CI 1.13-1.75, p = 0.03) were identified as independent risk factors for death in multivariable regression analysis. CONCLUSIONS: AKI severity in septic patients admitted in ER is associated with mortality. Diabetes, age over 65 years, and low MBP are independent risk factors for AKI and deserve further study to prevent AKI and, consequently, decreasing mortality.

Quantified power Doppler as a predictor of delayed graft function after renal transplantation.

PURPOSE: No safe ultrasound (US) parameters have been established to differentiate the causes of graft dysfunction. OBJECTIVES: To define US parameters and identify the predictors of normal graft evolution, delayed graft function (DGF), and rejection at the early period after kidney transplantation. METHODS: Between June 2012 and August 2013, 79 renal transplant recipients underwent US examination 1-3 days posttransplantation. Resistive index (RI), power Doppler (PD), and RI + PD (quantified PD) were assessed. Patients were allocated into three groups: normal graft evolution, DGF, and rejection. RESULTS: Resistive index of upper and middle segments and PD were higher in the DGF group than in the normal group. ROC curve analysis revealed that RI + PD was the index that best correlated with DGF (cutoff = 0.84). In the high RI + PD group, time to renal function recovery (6.33 ± 6.5 days) and number of dialysis sessions (2.81 ± 2.8) were greater than in the low RI + PD group (2.11 ± 5.3 days and 0.69 ± 1.5 sessions, respectively), p = 0.0001. Multivariate analysis showed that high donor final creatinine with a relative risk (RR) of 19.7 (2.01-184.7, p = 0.009) and older donor age (RR = 1.17 (1.04-1.32), p = 0.007) correlated with risk DGF. CONCLUSIONS: Quantified PD (RI + PD) was the best DGF predictor. PD quantification has not been previously reported.