Influence of HLA-A, B, and -DRB1 genes and panel-reactive antibodies on the waitlist time for kidney transplantation in the state of Sao Paulo-Brazil.

BACKGROUND: Brazil ranks second in the absolute number of transplants. However, the supply remains insufficient to meet the demands, resulting in a lengthy waitlist. This study aimed to analyze whether the frequency of human leukocyte antigen (HLA) and the value of calculated panel reactive antibody (cPRA) would influence the waiting time for kidney transplantation. METHODS: The HLA-A, B, and -DRB1 frequencies and the cPRA value were analyzed in 11,186 kidney transplant candidates included in the waitlist from 2006 to 2016. RESULTS: The most frequent alleles were HLA-A*02, HLA-B*35, and HLA-DRB1*13. The overall mean length of stay on the list was 986 ± 1001 days. The mean waiting time for the three most frequent alleles of the HLA-A and B loci showed no significant difference when compared with the least frequent alleles; however, for the HLA-DRB1 locus, the most frequent alleles showed a shorter waiting time. In the association between HLA and PRA, the average length of stay on the list increased according to the candidate's degree of sensitization, regardless of the analyzed HLA frequency. CONCLUSION: The length of stay on the waitlist is influenced by the frequency of the HLA alleles of the DRB1 locus and the degree of sensitization.

Different Patterns of Foxp3 Gene Expression in Pre-and Post-Transplantation Kidney Biopsies and the Effect of Use Mammalian Target of Rapamycin Inhibitors.

BACKGROUND: Trafficking of regulatory T cells (Tregs) modulates the inflammatory response after kidney transplantation (KTx). There is scarce information on whether circulating and intragraft Tregs are similarly affected by immunosuppressive drugs and the type of deceased kidney donor. METHODS: FOXP3 gene expression was measured in the pretransplant kidney biopsies (PIBx) from donors who met extended (ECD) and standard (SCD) criteria donors. In the third month after KTx, the patients were divided according to tacrolimus (Tac) or everolimus (Eve) and the type of kidney they had received. FOXP3 gene expression in the peripheral blood (PB) and kidney biopsies (Bx) was analyzed using real-time polymerase chain reaction. RESULTS: FOXP3 gene expression in the PIBx was higher in ECD kidneys. FOXP3 gene expression in the PB and Bx was greater in Eve- than in Tac-treated patients. However, SCD recipients treated with Eve (SCD/Eve) had higher FOXP3 expression than ECD/Eve. CONCLUSION: Pretransplant kidney biopsies from ECD kidneys had higher FOXP3 gene expression than SCD, and the use of Eve may affect the expression of the FOXP3 gene only in SCD kidneys.

Clinical outcomes of COVID-19 in patients undergoing chronic hemodialysis and peritoneal dialysis / Desfechos clínicos da COVID-19 em pacientes submetidos à hemodiálise crônica e diálise peritoneal

Abstract Background: The reported incidence and fatality rate of the severe acute respiratory syndrome coronavirus 2 in patients receiving chronic dialysis are higher than in the general population. We sought to study the outcomes following coronavirus disease 2019 (COVID-19) diagnosis in patients undergoing chronic hemodialysis (HD) or peritoneal dialysis (PD) in a single center in Brazil. Methods: Of the 522 patients on dialysis evaluated between March 1, 2020, and October 1, 2021, those presenting symptoms or with a history of close contact with COVID-19 patients were tested with reverse-transcription polymerase chain reaction of samples from nasopharyngeal swabs. Results: Of the 522 patients, 120 were positive for COVID-19 infection, of which 86% were on HD and 14% in the PD program. The incidence per 10,000 inhabitants was higher in the HD group than in the PD group (2,423.5 vs. 1,752.5). The mortality per 10,000 inhabitants (470.5 vs. 927.8) and the fatality rate (19.4 vs. 52.9%, p = 0.005) were higher in the PD group. The PD group also had a higher need for hospitalization, intensive care, and mechanical ventilation. Conclusions: We advise caution when considering strategies to transfer patients from HD to the PD program to minimize the risk of COVID-19 for patients on HD.

Resumo Antecedentes: A incidência e a taxa de letalidade da síndrome respiratória aguda grave por coronavírus 2 relatadas em pacientes em diálise crônica são mais elevadas do que na população em geral. Procuramos estudar os desfechos após o diagnóstico da doença por coronavírus 2019 (COVID-19) em pacientes submetidos à hemodiálise crônica (HD) ou diálise peritoneal (DP) em um único centro no Brasil. Métodos: Dos 522 pacientes em diálise avaliados entre 1º de Março de 2020 e 1º de Outubro de 2021, aqueles que apresentaram sintomas ou tiveram histórico de contato próximo com pacientes com COVID-19 foram testados com reação em cadeia da polimerase de transcrição reversa por meio de amostras de esfregaços nasofaríngeos. Resultados: Dos 522 pacientes, 120 foram positivos para infecção por COVID-19, dos quais 86% estavam em HD e 14% no programa de DP. A incidência por 10.000 habitantes foi maior no grupo HD do que no grupo DP (2.423,5 vs. 1.752,5). A mortalidade por 10.000 habitantes (470,5 vs. 927,8) e a taxa de letalidade (19,4 vs. 52,9%, p = 0,005) foram mais elevadas no grupo DP. O grupo DP também apresentou uma maior necessidade de hospitalização, terapia intensiva e ventilação mecânica. Conclusões: Recomendamos cautela ao considerar estratégias de transferência de pacientes do programa de HD para o de DP a fim de minimizar o risco de COVID-19 para pacientes em HD.

Evaluation of doxorubicin in three-dimensional culture of breast cancer cells and the response in PI3K/AKT/PTEN signaling pathways: a pilot study.

Breast cancer (BC) has a high mortality rate, which is attributed to the absence of effective treatment markers. Doxorubicin (DOX) was evaluated by molecular docking in vitro in cultured BC spheroids and its association with genes involved in the PI3K/AKT/PTEN signaling pathway. Spheroids were obtained from a primary BC. The selected compound was used for molecular docking experiments. Spheroids were treated with DOX for 1 (D1) and 9 (D9) days. qPCR was used to evaluate PIK3CA, HIF-1α, VEGF-A, PTEN expression. Treatment with DOX (1 µM) significantly increased the number of spheroids (D1), whereas exposure to chemotherapy at 2 µM on D9 was more effective. DOX treatment resulted in significantly higher expression of VEGF-A, HIF-1α and PIK3CA by D1 and HIF-1α and PTEN were upregulated by D9. Compared to treatment on D1 with D9 (1 µM) had significantly higher PTEN and lower PIK3CA gene expression. The genes HIF-1α and PTEN were more expressed with 2 µM of DOX while VEGF-A was downregulated. D1 vs. D9 exhibited reduced VEGF-A, HIF-1α, and PIK3CA expression and upregulation of PTEN expression. DOX effects at the molecular mechanisms can be involved the modulation of genes related to angiogenesis cell proliferation and tumor growth in BC tissue spheroids.

Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys.

BACKGROUND: Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantation and their inflammatory gene expression profile differently and may contribute to poor clinical outcomes. OBJECTIVE: Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI > 85%). METHODS: In a sample consisting of 45 consecutive pre-implantation biopsies, global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-κB protein expression by immunofluorescence. RESULTS: ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20 h and ECD kidney classification. CONCLUSIONS: This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors.

Clinical outcomes of COVID-19 in patients undergoing chronic hemodialysis and peritoneal dialysis.

BACKGROUND: The reported incidence and fatality rate of the severe acute respiratory syndrome coronavirus 2 in patients receiving chronic dialysis are higher than in the general population. We sought to study the outcomes following coronavirus disease 2019 (COVID-19) diagnosis in patients undergoing chronic hemodialysis (HD) or peritoneal dialysis (PD) in a single center in Brazil. METHODS: Of the 522 patients on dialysis evaluated between March 1, 2020, and October 1, 2021, those presenting symptoms or with a history of close contact with COVID-19 patients were tested with reverse-transcription polymerase chain reaction of samples from nasopharyngeal swabs. RESULTS: Of the 522 patients, 120 were positive for COVID-19 infection, of which 86% were on HD and 14% in the PD program. The incidence per 10,000 inhabitants was higher in the HD group than in the PD group (2,423.5 vs. 1,752.5). The mortality per 10,000 inhabitants (470.5 vs. 927.8) and the fatality rate (19.4 vs. 52.9%, p = 0.005) were higher in the PD group. The PD group also had a higher need for hospitalization, intensive care, and mechanical ventilation. CONCLUSIONS: We advise caution when considering strategies to transfer patients from HD to the PD program to minimize the risk of COVID-19 for patients on HD.

Effect of the COVID-19 Pandemic on Kidney Transplant and on Chronic Dialysis Patients.

BACKGROUND: The reported fatality rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients receiving maintenance dialysis or kidney transplant are higher than in the general population. The aim of this study was to evaluate the impact of SARS-CoV-2 infection in chronic dialysis patients (DPs) compared with kidney transplant recipients (KTxRs). METHODS: A study evaluating 266 COVID-19-positive patients (112 DPs and 154 KTxRs) was conducted in a single center from March 1, 2020, to June 30, 2021. All patients were confirmed for COVID-19 infection by reverse transcription polymerase chain reaction or antigen test. RESULTS: KTxRs were younger (49 ± 12.4 vs 61 ± 14.6 years; P < .0001) and had significantly fewer coexisting disorders than the DPs. A higher percentage of KTxRs required hospitalization (70% vs 49.4%, P = .002) and intensive care unit admission (39% vs 25%, P = .01). The fatality rate was 24% in both groups. DISCUSSION: There is no consensus among studies about the higher fatality rate between KTxRs and DPs who develop COVID-19. In our study, we also did not find a different fatality rate. CONCLUSION: In spite of KTxRs being younger and having fewer coexisting disorders, compared with DPs, they presented a higher hospitalization and intensive care unit necessity rate but a similar fatality rate.

SARS-CoV-2 assessment in an outpatient dialysis facility of a single center in Brazil.

BACKGROUND: The reported incidence and fatality rates of SARS-CoV-2 infection in patients receiving maintenance dialysis are higher than those of the general population. OBJECTIVE: This study sought to characterize the clinical characteristics and outcomes following COVID-19 infection in this population in a single center in Brazil. METHODS: Out of 497 dialysis patients evaluated between March 1st, 2020 and February 1st, 2021, those presenting symptoms or history of close contact with COVID-19 patients were tested. Disease severity was categorized as mild, moderate, or severe. RESULTS: Out of the 497 patients, 8.8% tested positive for COVID-19. These patients were predominantly male (59%), mean age 57.5 ± 17. Hospitalization was required for 45.4% of patients and 15.9% received mechanical ventilation. Symptoms such as fever, cough, dyspnea and asthenia were more frequent in the severe group. Neutrophil to lymphocyte ratio, C- reactive protein, glutamic oxalacetic transaminase and lactic dehydrogenase were significantly higher in the severe group, while hemoglobin and lymphocyte counts were significantly lower. Chest CT >50% of ground glass lesions was the risk factor associated with severe disease and need for hospitalization. The incidence of a thromboembolic event was of 22.7% in this population. The incidence, mortality, and case fatality rates were 954.4/10,000 patients, 151.8/10,000 patients, and 15.9%, respectively. CONCLUSIONS: The incidence, mortality and case fatality rates in our cohort were significantly higher than those reported for the general population. To institute appropriate control measures and early vaccination in dialysis facilities is imperative to prevent the spread of COVID-19 infection.

Efeitos da pandemia na saúde mental de acadêmicos de medicina do 1º ao 4º ano em faculdade do noroeste paulista / The effects of the pandemic on the mental health of medical academics from year 1 to year 4 at northwestern school / Efectos de la pandemia en la salud mental de académicos de medicina del 1 al 4 año en un colegio del noroeste de São Paulo

Introdução: A pandemia da COVID-19 se reproduz em diversos efeitos na população mundial, sendo um deles e de grande importância, os possíveis impactos psicológicos frente a um contexto de insegurança e imprevisibilidade. Objetivo: Investigar quais foram os efeitos da pandemia na saúde mental dos alunos de medicina do 1º ao 4º ano em uma faculdade do noroeste paulista. Métodos: Trata-se de um estudo descritivo, transversal, com abordagem quantitativa, realizado através um questionário on-line, visando identificar as possíveis mudanças na saúde mental dos alunos. Resultados: No total, 229 estudantes universitários participaram do estudo. Os resultados indicaram que 51,5% dos estudantes participantes entrevistados relataram ansiedade frequente; 40,2% ansiedade com muita frequência; 52% estresse frequente e 35,8% estresse com muita frequência. As perdas econômicas durante o período de pandemia e o consumo de substâncias psicoativas foram associados a maiores frequências de ansiedade e estresse. Os participantes relataram uma variedade de sintomas manifestados, mais frequentemente cansaço constante (80,3%), preocupação excessiva (69,9%), dificuldade para concentração (80,8%), irritação frequente (67,2%) e sensação de desgaste físico constante (72,9%). Além disso, a sobrecarga e desgaste frequentes em relação ao sistema remoto de ensino à distância foram relatados pela maioria dos estudantes (59,8%). Conclusão: Foram identificadas mudanças negativas na saúde mental da maioria dos acadêmicos em consequência de uma pandemia, manifestando sintomas de ansiedade e estresse frente às mudanças sociais impostas no período. As questões econômicas, os efeitos da quarentena na rotina diária e as mudanças acadêmicas são fatores de impacto psicológico para os estudantes.(AU)

Introduction: The COVID-19 pandemic reproduces itself in several effects in the world population, one of them being of great importance, the possible psychological impacts facing a context of insecurity and unpredictability. Objective: To investigate the effects of the pandemic on the mental health of medical students from the 1st to the 4th year in a college in the northwest of São Paulo. Methods: This is a descriptive, cross-sectional study, with a quantitative approach, conducted through an online questionnaire, aiming to identify possible changes in the students' mental health. Results: In total, 229 university students participated in the study. The results indicated that 51.5% of the participating students reported frequent anxiety; 40.2% anxiety very often; 52% frequent stress and 35.8% stress very often. Economic losses during the pandemic period and the consumption of psychoactive substances were associated with higher frequencies of anxiety and stress. Participants reported a variety of symptoms manifested, most often constant tiredness (80.3%), excessive concern (69.9%), difficulty concentrating (80.8%), frequent irritation (67.2%), and a feeling of constant physical wear (72.9%). In addition, frequent overload and wear in relation to the remote distance learning system were reported by most students (59.8%). Conclusion: Negative changes were identified in the mental health of most academics as a result of a pandemic, manifesting symptoms of anxiety and stress in the face of social changes imposed in the period. Economic issues, the effects of quarantine on daily routine and academic changes are psychological impact factors for students.(AU)

Introducción: La pandemia de COVID-19 se reproduce en varios efectos sobre la población mundial, uno de los cuales es de gran importancia, los posibles impactos psicológicos ante un contexto de inseguridad e imprevisibilidad. Objetivo: investigar los efectos de la cuarentena en la salud mental de estudiantes de medicina del 1º al 4º año de una facultad del noroeste de São Paulo. Métodos: Se trata de un estudio descriptivo, transversal con enfoque cuantitativo, realizado a través de un...(AU)

SARS-CoV-2 assessment in an outpatient dialysis facility of a single center in Brazil

ABSTRACT Background: The reported incidence and fatality rates of SARS-CoV-2 infection in patients receiving maintenance dialysis are higher than those of the general population. Objective: This study sought to characterize the clinical characteristics and outcomes following COVID-19 infection in this population in a single center in Brazil. Methods: Out of 497 dialysis patients evaluated between March 1st, 2020 and February 1st, 2021, those presenting symptoms or history of close contact with COVID-19 patients were tested. Disease severity was categorized as mild, moderate, or severe. Results: Out of the 497 patients, 8.8% tested positive for COVID-19. These patients were predominantly male (59%), mean age 57.5 ± 17. Hospitalization was required for 45.4% of patients and 15.9% received mechanical ventilation. Symptoms such as fever, cough, dyspnea and asthenia were more frequent in the severe group. Neutrophil to lymphocyte ratio, C- reactive protein, glutamic oxalacetic transaminase and lactic dehydrogenase were significantly higher in the severe group, while hemoglobin and lymphocyte counts were significantly lower. Chest CT >50% of ground glass lesions was the risk factor associated with severe disease and need for hospitalization. The incidence of a thromboembolic event was of 22.7% in this population. The incidence, mortality, and case fatality rates were 954.4/10,000 patients, 151.8/10,000 patients, and 15.9%, respectively. Conclusions: The incidence, mortality and case fatality rates in our cohort were significantly higher than those reported for the general population. To institute appropriate control measures and early vaccination in dialysis facilities is imperative to prevent the spread of COVID-19 infection.

Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD. METHODS: We transplanted mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPC and hiPSC cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology, and immunohistochemistry were evaluated 45 days post-surgery. RESULTS: We successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups. CONCLUSIONS: In conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seem to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improves clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.

Does protein supplementation and exercise interfere with renal function and structure? / A suplementação de proteína e o exercício interferem na função e estrutura renal? / ¿la suplementación de proteínas y el ejercicio interfieren en la función y estructura renal?

ABSTRACT Introduction: During physical activity, the body diverts blood to essential areas such as skeletal muscle, reducing the supply to non-essential areas such as the kidney. Whey protein is one of the most widely used supplements in gyms. Objectives: To evaluate renal function and renal structure in rats submitted to physical exercise with and without the use of protein supplementation. Methods: The protein used was Whey Hydro PRO 2 - Probiotica®. It was administered orally (by gavage), diluted in mineral water (1.8 g/kg of body weight, shortly after swimming training). The rats were divided into four groups: rats with exercise (Exc), rats without exercise (ñExc), rats with exercise and with protein supplementation (Prot/Exc) and rats without exercise and with protein supplementation (Prot/ñExc). The training consisted of swimming for 30 minutes, using load equivalent to 2% of body weight, five times a week for a total of 10 weeks. The protein was administered by gavage, once daily, immediately after the training. Results: A reduced glomerular filtration rate was observed in the animals of the Exc group compared to those of the Prot/Exc group. Plasma creatinine values were similar between the groups submitted to exercise and those not submitted to exercise. Plasma sodium and the sodium excretion fraction were lower in the Prot/Exc group compared to the Exc group. Urinary excretion was similar between groups. Histological analysis: Significant hydropic degeneration was observed in the animals that received protein supplementation and submitted to exercise. Conclusion: These results show that exercise associated with protein supplementation (2g/day/kg) leads to changes in the tubular mechanisms of sodium adjustments and structural changes in the renal parenchyma. Level of evidence II; Therapeutic studies - Investigation the results of treatment.

RESUMO Introdução: Durante a atividade física o corpo faz remanejamento sanguíneo para áreas essenciais como a musculatura esquelética, reduzindo o suprimento em áreas não essenciais como o rim. O whey protein (proteína do soro do leite) é um dos suplementos mais usados nas academias. Objetivos: Avaliar a função e a estrutura renal em ratos submetidos ao exercício físico sem e com o uso da suplementação de proteína. Métodos: A proteína usada foi Whey Hydro PRO 2 - Probiótica®, sendo administrada por via oral (gavagem), diluída em água mineral (1,8 g/kg de peso corporal logo após o treino de natação). Os ratos foram divididos em quatro grupos: ratos com exercício (Exc), ratos sem exercício (ñExc), ratos com exercício e com suplementação alimentar de proteína (Prot/Exc) e ratos sem exercício e com suplementação alimentar de proteína (Prot/ñExc). O treinamento consistia em natação por 30 minutos, com utilização de carga, equivalente a 2% do peso corporal, 5 vezes por semana em um total de 10 semanas. A proteína foi administrada por gavagem, uma vez ao dia e logo depois do treino. Resultados: Observou-se queda da filtração glomerular renal nos animais do grupo Exc vs. Prot/Exc. Os valores de creatinina plasmática foram semelhantes entre os grupos que praticaram o exercício vs. os que não praticaram. Para o sódio plasmático e a fração de excreção de sódio, os valores foram menores no grupo Prot/Exc quando comparados com o grupo Exc. A excreção urinária de ureia foi semelhante entre os grupos. Análise histológica: Observou-se degeneração hidrópica significativa nos animais que receberam a suplementação de proteína e realizaram o exercício. Conclusão: Esses resultados mostram que o exercício em conjunto com a suplementação de proteína (2 g/dia/Kg), determina alterações nos mecanismos tubulares de ajustes do sódio e alterações estruturais no parênquima renal. Nível de evidência II; Estudos terapêuticos - Investigação dos resultados do tratamento.

RESUMEN Introducción: Durante la actividad física el cuerpo hace reubicación sanguínea hacia áreas esenciales como la musculatura esquelética, reduciendo el suministro en áreas no esenciales como el riñón. La whey protein (proteína del suero de la leche) es uno de los suplementos más usados en los gimnasios. Objetivos: Evaluar la función y la estructura renal en ratones sometidos al ejercicio físico sin y con el uso de la suplementación de proteína. Métodos: La proteína utilizada fue Whey Hydro PRO 2 - Probiótica® siendo administrada vía oral (gavaje), diluida en agua mineral (1,8 g/kg de peso corporal luego después del entrenamiento de natación). Los ratones fueron divididos en cuatro grupos: ratones con ejercicio (Exc), ratones sin ejercicio (ñExc), ratones con ejercicio y con suplementación alimentaria de proteína (Prot/Exc) y ratones sin ejercicio y con suplementación alimenticia de proteína (Prot/ñExc). El entrenamiento consistía en natación por 30 minutos, con uso de carga, equivalente al 2% del peso corporal, 5 veces por semana en un total de 10 semanas. La proteína fue administrada por gavaje, una vez al día y luego después del entrenamiento. Resultados: Se observó caída de la filtración glomerular renal en los animales del grupo Exc vs Prot/Exc. Los valores de creatinina plasmática fueron semejantes entre los grupos que practicaron el ejercicio vs los no practicaron. Para el sodio plasmático y la fracción de excreción de sodio, los valores fueron menores en el grupo Prot/Exc cuando comparados con el Exc. La excreción urinaria de urea fue semejante entre los grupos. Análisis histológico: Se observó degeneración hidrópica significativa en los animales que recibieron la suplementación de proteínas y no realizaron el ejercicio. Conclusión: Estos resultados muestran que el ejercicio en conjunto con la suplementación de proteína (2 g/día/Kg), determina alteraciones en los mecanismos tubulares de ajustes del sodio y alteraciones estructurales en el parénquima renal. Nivel de evidencia II; Estudios terapéuticos - Investigación de los resultados del tratamiento.

Differentiating Induced Pluripotent Stem Cells into Renal Cells: A New Approach to Treat Kidney Diseases.

Renal disease is a major issue for global public health. Despite some progress in supportive care, the mortality rates among patients with this condition remain alarmingly high. Studies in pursuit of innovative strategies to treat renal diseases, especially stimulating kidney regeneration, have been developed. In this field, stem cell-based therapy has been a promising area. Induced pluripotent stem cell-derived renal cells (iPSC-RCs) represent an interesting source of cells for treating kidney diseases. Advances in regenerative medicine using iPSC-RCs and their application to the kidney are discussed in this review. Furthermore, the way differentiation protocols of induced pluripotent stem cells into renal cells may also be applied for the generation of kidney organoids is also described, contributing to studies in renal development, kidney diseases, and drug toxicity tests. The translation of the differentiation methodologies into animal model studies and the safety and feasibility of renal differentiated cells as a treatment for kidney injury are also highlighted. Although only few studies were published in this field, the results seem promising and support the use of iPSC-RCs as a potential therapy in the future.

Impact of Cold Ischemia Time on Kidney Transplant: A Mate Kidney Analysis.

INTRODUCTION: Longer cold ischemia time (CIT) is a deleterious factor for kidney transplant (KTx) outcomes and may lead Tx teams to graft discard. Because the CIT in Brazil is overall very high, the objective of this study was to compare outcomes among mate recipients of KTx with distinct CIT. METHODS: We studied 106 mate recipients of KTx in a single center followed for 1-year post-Tx. Mate kidneys were analyzed comparing the first and the second recipient to be transplanted. In a second analysis, we grouped mate recipients according to the CIT: ≤ 20 hours, > 20 hours, and mixed CIT. RESULTS: Seventy percent were standard criteria donors, with a mean Kidney Donor Profile Index (KDPI) of 61.5 ± 28%. KTx recipients presented an overall delayed graft function (DGF) rate of 82%, lasting 12 ± 7 days. The analysis of pairs considering the first and second recipient to be transplanted resulted in a longer CIT for the second (23.6 h vs 27 h; P = .001), and we did not find differences of outcomes after 1-year follow-up. Comparing pairs according to CIT (> 20h and ≤ 20h), DGF was higher in the CIT group > 20 hours (87.5% vs 58%; P = .002), with no differences of outcomes in 1-year follow-up. The logistic regression analysis shows that CIT > 20 hours is a risk factor for DGF in our study. CONCLUSION: CIT > 20 hours is a risk factor for DGF, therefore strategies to reduce the CIT are always necessary.

Activation of HMGB1-TLR4 Pathway and Inflammasome Contribute to Enhanced Inflammatory Response in Extended Criteria and Kidneys With KDPI ≥85.

BACKGROUND: Metrics for evaluating low-quality kidneys have failed to predict outcomes or reduce the kidney refusal and discard rates. Kidneys from extended-criteria donors (ECDs) and kidneys with ≥85% kidney donor profile indexes (KDPIs) might have different sensitivities to the proinflammatory milieu generated by brain death. We aimed to identify gene expression profile differences in innate immunity pathways between low-quality and ideal kidneys. METHODS: Preimplantation kidney biopsies from ECD (n = 41) and standard-criteria donor (n = 39) were evaluated for real-time quantitative polymerase chain reaction gene expression using the TaqMan Gene Expression Array Plates system for genes Toll-like receptor-4 (TLR4), high-mobility group box 1, nuclear factor kappa beta, myeloid differentiation primary response 88, interferon (IFN)-γ, interleukin (IL)1-ß, tumor necrosis factor alpha, caspase-1 (CASP1), intercellular adhesion molecule 1, IL-10, heme oxygenase 1 hypoxia-inducible factor 1 (HIF-1), monocyte chemotactic protein 1, transforming growth factor beta 1, TIR-domain containing adapter inducing interferon-ß (TRIF), TRIF-related adaptor molecule, interferon regulatory factor 3 (IRF-3), receptor-interacting protein 1, IFNß-1, and nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin protein 3 complex. Gene expression was also evaluated in kidneys with KDPI ≥85. RESULTS: ECD biopsies showed significantly higher expression of IL-10, TLR4, high-mobility group box 1, IFN-γ, TRIF-related adapter molecule, IRF-3, HIF-1, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin protein 3 complex, CASP1, and IL-1ß (P < 0.05) compared with standard-criteria donor biopsies. IRF-3, HIF-1, and CASP1 were exclusively upregulated in ECD kidneys. Compared with kidneys with KDPIs <85%, kidneys with KDPIs ≥85% had very similar gene transcripts as those observed in ECD kidneys, except that tumor necrosis factor alpha and monocyte chemotactic protein 1 expression was only elevated in kidneys with KDPIs ≥85%. Significant positive correlations were found between the different genes upregulated and the increase in KDPIs. CONCLUSIONS: Our results showed that TLR4 and inflammasome pathways are enhanced in low-quality kidneys and suggest that blocking of some targets might improve transplant outcomes and reduce discard rates.

Clinical and laboratorial profiles of dengue virus infection in kidney transplant recipients: Report of a single center.

Dengue infection (DI) is the most important arboviral infection in the world. The majority of immunocompetent patients will have asymptomatic or mild infections, but the degree of dengue severity in kidney transplant recipients (KTx) is unknown. In this study, we report the clinical profile and outcomes of 39 dengue cases in KTx. From a total of 1,186 KTx outpatients in follow-up we reviewed clinical and laboratory records of 60 (5%) patients admitted with suspected DI initially screened by NS-1, IgM, and when possible, multiplex nested PCR. The prevalence of DI in KTx was 3% (39/1,118), with symptoms leading to hospital admission being fever, myalgia, malaise, and headache. Laboratory tests showed leucopenia, thrombocytopenia, and liver enzyme elevation. DI was confirmed by positivity of NS-1 (33%), IgM (69%), and/or RT-PCR (59%). Twenty-three patients (59%) had dengue with warning signs, and 15% had severe dengue, 2 of them with a fatal course. Acute graft dysfunction occurred in 59% (mean nadir serum creatinine: 2.9 ± 2.6mg/dL), 4 of them requiring dialysis. CMV coinfection diagnosed in 19% of the cases and patients was associated with worse clinical presentation. Our results suggest that KTx with DI presented initial physical and laboratorial profile similar to the general population. However, DI in KTx seems to have a higher risk for graft dysfunction, severe dengue, and death. Because CMV coinfection aggravates the DI clinical presentation and recovery, it must be evaluated in all cases.

A Clínica Psicanalítica na Rua diante da Violência e Segregação / The Psychoanalytic Clinic on the Street Facing Violence and Segregation / La Clínica Psicoanalítica en la Calle Ante la Violencia y Segregación / La Clinique Psychanalytique dans la Rue Face à la Violence et à la Ségrégation

Esse artigo parte de três experiências distintas de trabalho na cidade, em que verificamos imporem-se questões relativas tanto à violência quanto à segregação. A clínica desenvolvida com população em situação de rua nos apresenta tanto o desarranjo desses sujeitos com suas próprias formas de gozo, que frequentemente resvalam na problemática da violência, quanto a incoerência das respostas políticas do Estado, que, em nome da "garantia de direitos", muitas vezes se aproxima de processos de segregação. Buscamos elucidar os efeitos produzidos pela presença da orientação da psicanálise. O que acontece quando um psicanalista toma sua posição ética infiltrando-se clandestinamente, como uma peste, nas brechas dos tecidos discursivos urbanos? Pretendemos lançar luz sobre a forma através da qual temos podido responder ao desafio da ética que orienta a psicanálise para dar testemunho sobre o sintoma de nosso tempo e como fazer uso dele no caso a caso e na vida de uma cidade.

This article is based on three different experiences of work in the city, in which we find ourselves imposing questions regarding both violence and segregation. The clinic developed with a street population shows us both the disarrangement of these subjects with their own forms of enjoyment, which often slip in the problematic of violence, as well as the incoherence of the political responses of the State, which, in the name of the "guarantee of rights" , often approaching segregation processes. We seek to elucidate the effects produced by the presence of the psychoanalysis orientation. What happens when a psychoanalyst takes his ethical position by clandestinely infiltrating, like a plague, into the gaps of urban discursive tissues? We intend to shed light on how we have been able to respond to the challenge of ethics that guides psychoanalysis to bear witness to the symptom of our time and how to make use of it in case by case and in the life of a city.

Este artículo viene de tres experiencias distintas de trabajo en la ciudad, en la que observamos la imposición de cuestiones relativas tanto a la violencia cuanto a la segregación. La clínica desarrollada con populación callejera nos presenta tanto el desarreglo de estos sujetos con sus propias formas de gozo, que frecuentemente resbalan en la problemática de la violencia, cuanto a la incoherencia de las respuestas políticas del Estado, que, al nombre de la "garantía de derechos", muchas veces se acerca a procesos de segregación. Buscamos aclarar los efectos producidos por la presencia del psicoanálisis. ¿Qué pasa cuando un psicoanalista toma una posición ética infiltrándose clandestinamente, como una plaga, en los huecos de las tramas discursivas urbanas? Pretendemos lanzar luz sobre la forma por la cual hemos podido responder al reto de la ética que orienta el psicoanálisis para dar testimonio sobre el síntoma de nuestro tiempo y cómo hacer uso de él en cada caso y en la vida de una ciudad.

Cet article part de trois différentes expériences de travail dans la ville, où on a vu s'imposer des questions à propos de la violence et de la ségrégation. La clinique élaborée avec des Sans Domicile Fixe (SDF) nous présente le dérèglement de ces personnes avec leurs propres formes de jouissance, ceux qui fréquemment finissent chez la violence. D'autre côté, la clinique nous présente aussi l'incohérence des réponses politiques de l'État qui, au nom de la «garantie des droits¼, s'approche souvent d'un processus de ségrégation. On cherche à élucider les effets produits par la présence de l'orientation de la psychanalyse. Que se passe-t-il quand un psychanalyste prend son position éthique, et s'infiltre clandestinement, comme une peste, dans les trous des tissus urbains discursifs? On a l'objectif d'attirer l'attention sur la façon comment on a répondu au défi de l'éthique qui oriente la psychanalyse. Pour qu'on puisse témoigner sur le symptôme de notre temps et comment l'utiliser dans les cas particuliers et dans la vie d'une ville.