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BACKGROUND: Brain death (BD) and cold storage (CS) are critical factors that induce inflammation in donor kidneys, compromising organ quality. We investigated whether treating kidneys from BD rats with an inflammasome Nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor (MCC950) followed by CS could reduce kidney inflammation. METHODS: BD rats were assigned to MCC950-treated or nontreated (NT) groups. Kidneys were evaluated immediately before CS (T0) and after 12 h (T12) and 24 h (T24) of CS. Mean arterial pressure, serum creatinine, gene/protein expression, and histology were evaluated. RESULTS: At T0, MCC950 treatment did not affect mean arterial pressure but tended to reduce serum creatinine and ameliorated the histological score of acute tubular necrosis. However, MCC950 reduced NLRP3, caspase-1, interleukin (IL)-1ß, IL-6, Kim-1, nuclear factor kappa B, tumor necrosis factor alpha, and caspase-3 gene expression while increasing IL-10 cytokine gene expression. After 12 h of CS, only the expression of the NLRP3 and caspase-1 genes decreased, and after 24 h of CS, no further changes in the gene expression profile were observed. The levels of the inflammasome proteins NLRP3, caspase-1, and IL-1ß consistently decreased across all time points (T0, T12, and T24). CONCLUSIONS: These findings suggest that MCC950 treatment holds promise for mitigating the proinflammatory state observed in kidneys after BD and CS.
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BACKGROUND: COVID-19, caused by SARS-CoV-2, was responsible for higher morbidity and mortality in renal transplant recipients (RTx). The objective of the study was to evaluate the impact of COVID-19 infection on RTx in a single center in Brazil. METHODS: A cohort of 135 RTx was evaluated between December 2019 and June 202l, and demographics, clinical, and laboratory profiles were analyzed from deceased donors with COVID-19. RESULTS: Diabetic and RTx from extended criterion donors presented more frequently the severe form of the disease. Serum creatinine (sCr) after 3 months of diagnosis of COVID-19 varied according to the severity of infection. The lethality rate was higher in the group with severe symptoms (65%) compared with those with mild infection (1.5%). CONCLUSION: The increase in sCr was associated with disease severity. The lethality rate for COVID-19 was 26.6%. These rates are 10-20 times higher than those reported in the general population and suggest that rigorous observation, early diagnosis, and disease prevention measures are crucial in RTx.
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COVID-19 , Trasplante de Riñón , Humanos , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/diagnóstico , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Femenino , Brasil/epidemiología , Adulto , Receptores de Trasplantes/estadística & datos numéricos , SARS-CoV-2 , Creatinina/sangre , Índice de Severidad de la Enfermedad , Anciano , Estudios RetrospectivosRESUMEN
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.
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Trasplante de Riñón , Humanos , Cadenas HLA-DRB1/genética , Brasil , Listas de Espera , Antígenos HLA-A/genética , Antígenos HLA , Alelos , Anticuerpos , Frecuencia de los GenesRESUMEN
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.
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Supervivencia de Injerto , Sirolimus , Humanos , Sirolimus/uso terapéutico , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Donantes de Tejidos , Everolimus/efectos adversos , Riñón , Factores de Transcripción Forkhead/genética , Serina-Treonina Quinasas TOR , Expresión Génica , BiopsiaRESUMEN
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.
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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.
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Neoplasias de la Mama , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Doxorrubicina/farmacología , Femenino , Humanos , Simulación del Acoplamiento Molecular , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proyectos Piloto , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/fisiología , Esferoides Celulares , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/genéticaAsunto(s)
COVID-19 , Síndrome Respiratorio Agudo Grave , Brasil/epidemiología , Humanos , Diálisis Renal , SARS-CoV-2RESUMEN
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.
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COVID-19 , Fallo Renal Crónico , Diálisis Peritoneal , Humanos , Diálisis Renal/efectos adversos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Diálisis Peritoneal/efectos adversos , Hospitalización , Estudios RetrospectivosRESUMEN
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.
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COVID-19 , Trasplante de Riñón , COVID-19/epidemiología , Humanos , Trasplante de Riñón/efectos adversos , Pandemias , Diálisis Renal/efectos adversos , SARS-CoV-2 , Receptores de TrasplantesRESUMEN
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.
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Trasplante de Riñón , FN-kappa B , Biopsia , ADN , Metilación de ADN , Humanos , Riñón/patología , FN-kappa B/genéticaRESUMEN
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.
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COVID-19 , SARS-CoV-2 , Adulto , Anciano , Brasil/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios , Diálisis Renal/efectos adversosRESUMEN
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.
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Humanos , Masculino , Adulto , Anciano , SARS-CoV-2 , COVID-19 , Pacientes Ambulatorios , Brasil/epidemiología , Diálisis Renal/efectos adversos , Persona de Mediana EdadRESUMEN
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.
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Células Madre Pluripotentes Inducidas , Células Madre Pluripotentes , Insuficiencia Renal Crónica , Animales , Diferenciación Celular , Humanos , Riñón , Proteínas de Microfilamentos , Ratas , Insuficiencia Renal Crónica/terapiaRESUMEN
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.
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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.
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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.
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Isquemia Fría/efectos adversos , Funcionamiento Retardado del Injerto/epidemiología , Trasplante de Riñón/efectos adversos , Factores de Tiempo , Adulto , Brasil/epidemiología , Funcionamiento Retardado del Injerto/etiología , Femenino , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Donantes de Tejidos/estadística & datos numéricosRESUMEN
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.
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Anticuerpos Antivirales/sangre , Infecciones por Citomegalovirus/sangre , Citomegalovirus , Virus del Dengue , Inmunoglobulina M/sangre , Trasplante de Riñón , Dengue Grave/sangre , Adulto , Coinfección , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Dengue Grave/epidemiología , Dengue Grave/terapiaRESUMEN
The therapeutic effect of induced pluripotent stem cells (iPSs) on the progression of chronic kidney disease (CKD) has not yet been demonstrated. In this study, we sought to assess whether treatment with iPSs retards progression of CKD when compared with bone marrow mesenchymal stem cells (BMSCs). Untreated 5/6 nephrectomized rats were compared with CKD animals receiving BMSCs or iPSs. Renal function, histology, immunohistochemistry, and gene expression were studied. Implanted iPSs were tracked by the SRY gene expression analysis. Both treatments minimized elevation in serum creatinine, significantly improved clearance, and slowed down progression of disease. The proteinuria was reduced only in the iPS group. Both treatments reduced glomerulosclerosis, iPSs decreased macrophage infiltration, and TGF-ß was reduced in kidneys from the BMSC group. Both types of treatments increased VEGF gene expression, TGF-ß was upregulated only in the iPS group, and IL-10 had low expression in both groups. The SRY gene was found in 5/8 rats treated with iPSs. These 5 animals presented tumors with histology and cells highly staining positive for PCNA and Wilms' tumor protein antibody characteristics of Wilms' tumor. These results suggest that iPSs may be efficient to retard progression of CKD but carry the risk of Wilms' tumor development.