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1.
Nat Commun ; 11(1): 4467, 2020 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948751

RESUMO

Recent studies have reported that upregulation of disulfide-bond A oxidoreductase-like protein (DsbA-L) prevented lipid-induced renal injury in diabetic nephropathy (DN). However, the role and regulation of proximal tubular DsbA-L for renal tubulointerstitial fibrosis (TIF) remains unclear. In current study, we found that a proximal tubules-specific DsbA-L knockout mouse (PT-DsbA-L-KO) attenuated UUO-induced TIF, renal cell apoptosis and inflammation. Mechanistically, the DsbA-L interacted with Hsp90 in mitochondria of BUMPT cells which activated the signaling of Smad3 and p53 to produce connective tissue growth factor (CTGF) and then resulted in accumulation of ECM of BUMPT cells and mouse kidney fibroblasts. In addition, the progression of TIF caused by UUO, ischemic/reperfusion (I/R), aristolochic acid, and repeated acute low-dose cisplatin was also alleviated in PT-DsbA-L-KO mice via the activation of Hsp90 /Smad3 and p53/CTGF axis. Finally, the above molecular changes were verified in the kidney biopsies from patients with obstructive nephropathy (Ob). Together, these results suggest that DsbA-L in proximal tubular cells promotes TIF via activation of the Hsp90 /Smad3 and p53/CTGF axis.


Assuntos
Fibrose/genética , Predisposição Genética para Doença/genética , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Nefropatias/genética , Idoso , Animais , Apoptose , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Nefropatias Diabéticas , Modelos Animais de Doenças , Feminino , Fibrose/patologia , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Inflamação , Rim/lesões , Nefropatias/patologia , Túbulos Renais Proximais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Transdução de Sinais , Proteína Smad3/metabolismo , Proteína Supressora de Tumor p53/metabolismo
2.
Radiol Clin North Am ; 58(5): 965-979, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32792127

RESUMO

Blunt trauma accounts for more than 95% of traumatic renal injury and results from shear forces from rapid acceleration or deceleration and/or collision against the spine or ribs. The use of multiphasic contrast-enhanced computed tomography (CT) has proven pivotal in the evaluation and management of traumatic kidney injury, and CT imaging features provide the basis for nonsurgical staging. This article describes the epidemiology and mechanisms of blunt and penetrating traumatic renal injury and reviews the range of findings from various imaging modalities, with a particular emphasis on contrast-enhanced CT.


Assuntos
Rim/lesões , Imagem Multimodal/métodos , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/diagnóstico por imagem , Humanos , Rim/diagnóstico por imagem , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X , Ultrassonografia
3.
Vasc Endovascular Surg ; 54(7): 643-645, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32638641

RESUMO

A 78-year-old male patient was admitted to our hospital after abdominal trauma. Contrast-enhanced computed tomography (CT) scan demonstrated a horseshoe kidney with a perinephric hematoma and evidence of arterial hemorrhage. An anomalous renal arterial anatomy was noted as well, with a renal artery originating from the left common iliac artery. He was successfully treated via an endovascular approach. Varying forms of vascularization may complicate angiographic treatment of patients with abdominal trauma in a setting of kidney anomalies. Obtaining and evaluating contrast-enhanced CT angiography can identify anomalous vessels and can be invaluable when deciding on the most appropriate interventional approach.


Assuntos
Traumatismos Abdominais/terapia , Acidentes por Quedas , Embolização Terapêutica , Procedimentos Endovasculares , Rim Fundido/complicações , Rim/lesões , Lacerações/terapia , Artéria Renal/lesões , Lesões do Sistema Vascular/terapia , Ferimentos não Penetrantes/terapia , Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/etiologia , Idoso , Embolização Terapêutica/instrumentação , Procedimentos Endovasculares/instrumentação , Rim Fundido/diagnóstico por imagem , Humanos , Rim/diagnóstico por imagem , Lacerações/diagnóstico por imagem , Lacerações/etiologia , Masculino , Artéria Renal/anormalidades , Artéria Renal/diagnóstico por imagem , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia , Ferimentos não Penetrantes/diagnóstico por imagem , Ferimentos não Penetrantes/etiologia
4.
Am J Physiol Renal Physiol ; 319(2): F202-F214, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32628541

RESUMO

Kidney stone disease is a crystal concretion formed in the kidneys that has been associated with an increased risk of chronic kidney disease. MicroRNAs are functionally involved in kidney injury. Data mining using a microRNA array database suggested that miR-21 may be associated with calcium oxalate monohydrate (COM)-induced renal tubular cell injury. Here, we confirmed that COM exposure significantly upregulated miR-21 expression, inhibited proliferation, promoted apoptosis, and caused lipid accumulation in an immortalized renal tubular cell line (HK-2). Moreover, inhibition of miR-21 enhanced proliferation and decreased apoptosis and lipid accumulation in HK-2 cells upon COM exposure. In a glyoxylate-induced mouse model of renal calcium oxalate deposition, increased miR-21 expression, lipid accumulation, and kidney injury were also observed. In silico analysis and subsequent experimental validation confirmed the peroxisome proliferator-activated receptor (PPAR)-α gene (PPARA) a key gene in fatty acid oxidation, as a direct miR-21 target. Suppression of miR-21 by miRNA antagomiR or activation of PPAR-α by its selective agonist fenofibrate significantly reduced renal lipid accumulation and protected against renal injury in vivo. In addition, miR-21 was significantly increased in urine samples from patients with calcium oxalate renal stones compared with healthy volunteers. In situ hybridization of biopsy samples from patients with nephrocalcinosis revealed that miR-21 was also significantly upregulated compared with normal kidney tissues from patients with renal cell carcinoma who underwent radical nephrectomy. These results suggested that miR-21 promoted calcium oxalate-induced renal tubular cell injury by targeting PPARA, indicating that miR-21 could be a potential therapeutic target and biomarker for nephrolithiasis.


Assuntos
Oxalato de Cálcio/farmacologia , Rim/lesões , MicroRNAs/farmacologia , PPAR alfa/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/genética , Biomarcadores/metabolismo , Oxalato de Cálcio/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Humanos , Rim/metabolismo , Cálculos Renais/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , MicroRNAs/genética , Nefrocalcinose/metabolismo , Transdução de Sinais/efeitos dos fármacos
5.
Am J Physiol Renal Physiol ; 319(2): F345-F357, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32715763

RESUMO

Angiotensin II (ANG II) is the key contributor to renal fibrosis and injury. The present study investigated the role of endothelium prolyl hydroxylase 2 (PHD2) in ANG II-mediated renal fibrosis and injury. In vitro, endothelial cells (ECs) were isolated from PHD2f/f control [wild-type (WT)] mice or PHD2 EC knockout (PHD2ECKO) mice. In vivo, WT and PHD2ECKO mice were infused with ANG II (1,000 ng·kg-1·min-1) for 28 days. Renal fibrosis, reactive oxygen species (ROS), and iron contents were measured. Knockout of PHD2 resulted in a significant increase in the expression of hypoxia-inducible factor (HIF)-1α and HIF-2α in ECs. Intriguingly, knockout of PHD2 significantly reduced expression of the ANG II type 1 receptor (AT1R) in ECs. WT mice infused with ANG II caused increases in renal fibrosis, ROS formation, and iron contents. ANG II treatment led to a downregulation of PHD1 expression and upregulation of HIF-1α and HIF-2α in the renal cortex and medulla. Knockout of PHD2 in EC blunted ANG II-induced downregulation of PHD1 expression. Furthermore, knockout of PHD2 in ECs attenuated ANG II-induced expression of HIF-1α, HIF-2α, transforming growth factor-ß1, p47phox, gp91phox, heme oxygenase-1, and ferroportin. This was accompanied by a significant suppression of renal fibrosis, ROS formation, and iron accumulation. In summary, knockout of endothelial PHD2 suppressed the expression of AT1R in ECs and blunted ANG II-induced downregulation of PHD1 and upregulation of HIF-α in the kidney. Our study, for the first time, demonstrates a necessary role of endothelial PHD2 in ANG II-mediated renal fibrosis and injury.


Assuntos
Angiotensina II/metabolismo , Células Endoteliais/metabolismo , Fibrose/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo , Nefropatias/enzimologia , Rim/lesões , Angiotensina II/farmacologia , Animais , Células Endoteliais/efeitos dos fármacos , Endotélio/metabolismo , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Rim/enzimologia , Camundongos , Camundongos Knockout , Pró-Colágeno-Prolina Dioxigenase/genética , Pró-Colágeno-Prolina Dioxigenase/metabolismo , RNA Interferente Pequeno/metabolismo
6.
Am J Physiol Renal Physiol ; 319(2): F155-F161, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32538149

RESUMO

Systemic lupus erythematosus (SLE) is characterized by hypertension that results from chronic renal inflammation and dysautonomia in the form of dampened vagal tone. In health, the vagus nerve regulates inflammatory processes through mechanisms like the cholinergic anti-inflammatory pathway; so in the case of SLE, reduced efferent vagus nerve activity may indirectly affect renal inflammation and therefore hypertension. In this study, we sought to investigate the impact of disrupting vagal neurotransmission on renal inflammation and hypertension in the setting of chronic inflammatory disease. Female SLE (NZBWF1) and control (NZW) mice were subjected to a right unilateral cervical vagotomy or sham surgery and 3 wk later were implanted with indwelling catheters to measure blood pressure. Indices of splenic and renal inflammation, as well as renal injury, were assessed. Unilateral vagotomy blunted SLE-induced increases in mean arterial pressure, albumin excretion rate, and glomerulosclerosis. This protection was associated with reduced splenic T cells and attenuated SLE-induced increases in renal proinflammatory mediators. In summary, these data indicate that unilateral vagotomy reduces renal inflammation and reduces blood pressure in SLE mice. The vagus nerves have myriad functions, and perhaps other neuroimmune interactions compensate for the ligation of one nerve.


Assuntos
Pressão Sanguínea/fisiologia , Inflamação/metabolismo , Rim/lesões , Rim/metabolismo , Lúpus Eritematoso Sistêmico/metabolismo , Albuminúria/fisiopatologia , Animais , Modelos Animais de Doenças , Hipertensão/complicações , Hipertensão/fisiopatologia , Nefropatias/metabolismo , Lúpus Eritematoso Sistêmico/complicações , Camundongos Endogâmicos , Nefrite/metabolismo , Nefrite/fisiopatologia
7.
Am J Physiol Renal Physiol ; 319(2): F229-F244, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32538150

RESUMO

Sepsis-associated acute kidney injury (s-AKI) has a staggering impact in patients and lacks any treatment. Incomplete understanding of the pathogenesis of s-AKI is a major barrier to the development of effective therapies. We address the gaps in knowledge regarding renal oxygenation, tubular metabolism, and mitochondrial function in the pathogenesis of s-AKI using the cecal ligation and puncture (CLP) model in mice. At 24 h after CLP, renal oxygen delivery was reduced; however, fractional oxygen extraction was unchanged, suggesting inefficient renal oxygen utilization despite decreased glomerular filtration rate and filtered load. To investigate the underlying mechanisms, we examined temporal changes in mitochondrial function and metabolism at 4 and 24 h after CLP. At 4 h after CLP, markers of mitochondrial content and biogenesis were increased in CLP kidneys, but mitochondrial oxygen consumption rates were suppressed in proximal tubules. Interestingly, at 24 h, proximal tubular mitochondria displayed high respiratory capacity, but with decreased mitochondrial content, biogenesis, fusion, and ATP levels in CLP kidneys, suggesting decreased ATP synthesis efficiency. We further investigated metabolic reprogramming after CLP and observed reduced expression of fatty acid oxidation enzymes but increased expression of glycolytic enzymes at 24 h. However, assessment of functional glycolysis revealed lower glycolytic capacity, glycolytic reserve, and compensatory glycolysis in CLP proximal tubules, which may explain their susceptibility to injury. In conclusion, we demonstrated significant alterations in renal oxygenation, tubular mitochondrial function, and metabolic reprogramming in s-AKI, which may play an important role in the progression of injury and recovery from AKI in sepsis.


Assuntos
Lesão Renal Aguda/patologia , Rim/lesões , Mitocôndrias/metabolismo , Sepse/complicações , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Animais , Modelos Animais de Doenças , Rim/metabolismo , Túbulos Renais Proximais/metabolismo , Camundongos Endogâmicos C57BL , Sepse/metabolismo
8.
Proc Natl Acad Sci U S A ; 117(27): 15874-15883, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32571916

RESUMO

After acute kidney injury (AKI), patients either recover or alternatively develop fibrosis and chronic kidney disease. Interactions between injured epithelia, stroma, and inflammatory cells determine whether kidneys repair or undergo fibrosis, but the molecular events that drive these processes are poorly understood. Here, we use single nucleus RNA sequencing of a mouse model of AKI to characterize cell states during repair from acute injury. We identify a distinct proinflammatory and profibrotic proximal tubule cell state that fails to repair. Deconvolution of bulk RNA-seq datasets indicates that this failed-repair proximal tubule cell (FR-PTC) state can be detected in other models of kidney injury, increasing during aging in rat kidney and over time in human kidney allografts. We also describe dynamic intercellular communication networks and discern transcriptional pathways driving successful vs. failed repair. Our study provides a detailed description of cellular responses after injury and suggests that the FR-PTC state may represent a therapeutic target to improve repair.


Assuntos
Lesão Renal Aguda/metabolismo , Túbulos Renais Proximais/metabolismo , Rim/metabolismo , Transcriptoma , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Aloenxertos , Animais , Modelos Animais de Doenças , Fibrose , Redes Reguladoras de Genes , Humanos , Rim/lesões , Túbulos Renais Proximais/lesões , Túbulos Renais Proximais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Análise de Sequência de RNA , Células Estromais/metabolismo , Células Estromais/patologia
9.
Arch. esp. urol. (Ed. impr.) ; 73(4): 247-280, mayo 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-192987

RESUMO

OBJETIVO: Caracterizar la condición clínica, el tipo de abordaje terapéutico y desenlaces de pacientes con trauma renal de alto grado (AAST: 4 y 5) atendidos en un hospital de tercer nivel. Cali, Colombia. MÉTODOS: Se realizó un estudio observacional descriptivo con pacientes mayores de 15 años atendidos entre el 1 de enero de 2015 y el 1 enero de 2019, con diagnóstico de traumatismo renal y traumatismo de vasos renales. Se recolectaron variables demográficas, clínicas y de severidad del trauma. Se realizó un análisis univariado con tablas de frecuencia, medidas de tendencia central, dependiendo de tipo de intervención, lesiones asociadas, uso de hemoderivados e índices de severidad. RESULTADOS: Se analizaron 71 historias clínicas, 82% de sexo masculino, el promedio de edad fue 25 años (rango: 15-55). Respecto al grado trauma renal, el 69%de los pacientes fueron grado IV y el 31% grado V. Las lesiones penetrantes se vieron en un 87% vs 13% delesiones por mecanismo contuso (no penetrante). El 54% de los pacientes fueron puntuados con un Índice de Severidadde Trauma >= 25 y el 51% de los pacientes presentó un Índice de Trauma Abdominal <= 24. Se observó manejo quirúrgico en 67% vs 32% para manejo no quirúrgico. El tiempo de estancia hospitalaria fue de 17 días en promedio y el 16,9% tuvo complicaciones. CONCLUSIONES: El traumatismo renal de alto grado es una condición clínica frecuente en pacientes masculinos entre la segunda y tercera década de vida, en nuestro medio la mayoría corresponden a traumas penetrantes. La mayoría de casos fueron manejados con algún procedimiento quirúrgico, sin embargo, con un importante porcentaje de manejo conservador con tasas de complicaciones menores del 30 %, que cambia el paradigma del tratamiento del trauma renal de alto grado


OBJECTIVE: To characterize the clinical condition, the type of therapeutic approach and outcome of patients with severe renal trauma (AAST: 4 and 5) treated in a tertiary hospital. Cali, Colombia. METHODS: A descriptive observational study was conducted with patients older than 15 years treated between January 1, 2015 and January 1, 2019, with a diagnosis of renal trauma and renal vessel trauma. Demographic, clinical and trauma severity variables were collected. A univariate analysis was carried out with frequency tables, measures of central tendency, depending on type of intervention, associated lesions, use of blood products and severity indices. RESULTS: 71 medical records were analyzed, 82% male, the average age was 25 years (range: 15-55). Regarding renal traumatic grade, 69% of the patients were grade IV and 31% grade V. Penetrating injuries were seen in 87% versus 13% of injuries due to blunt (non-penetrating) mechanism. 54% of the patients were scored with a trauma severity index >= 25 and 51% of the patients had an abdominal trauma index <= 24. Surgical management was managed in 67% vs. 32% for non-trauma management. surgical. The hospital stay was 17 days on average and 16.9% had complications. CONCLUSIONS: Severe renal trauma is a frequent clinical condition in male patients between the second and third decade of life, in our environment the majority corresponds to penetrating traumas. Most cases were managed with some surgical procedure, however, with a significant percentage of conservative management with complication rates of less than 30%, which changes the paradigm of treatment of high-grade renal trauma


Assuntos
Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Rim/lesões , Rim/cirurgia , Ferimentos e Lesões/epidemiologia , Colômbia , Índice de Gravidade de Doença , Tempo de Internação , Sistema Urinário/lesões
10.
Artigo em Inglês | MEDLINE | ID: mdl-32466510

RESUMO

Saudi Arabia (SA) is one of the hottest countries in the world. This study was conducted to assess the impact of summer heat stress in Southeastern SA on short-term kidney injury (KI) among building construction workers and to identify relevant risk factors. Measurements of urinary albumin-creatinine ratio (ACR), height, weight, hydration, symptoms, daily work and behavioral factors were collected in June and September of 2016 from a cohort of construction workers (n = 65) in Al-Ahsa Province, SA. KI was defined as ACR ≥30 mg/g. Multivariate linear regression analysis was used to assess factors related to cross-summer changes in ACR. A significant increase in ACR occurred among most workers over the study period; incidence of KI was 18%. Risk factors associated with an increased ACR included dehydration, short sleep, and obesity. The findings suggest that exposure to summer heat may lead to the development of KI among construction workers in this region. Adequate hydration and promotion of healthy habits among workers may help reduce the risk of KI. A reduction in work hours may be the most effective intervention because this action can reduce heat exposure and improve sleep quality.


Assuntos
Indústria da Construção , Transtornos de Estresse por Calor , Rim , Exposição Ocupacional , Adulto , Albuminúria , Transtornos de Estresse por Calor/complicações , Resposta ao Choque Térmico , Humanos , Rim/lesões , Estudos Longitudinais , Pessoa de Meia-Idade , Arábia Saudita
11.
Arch Esp Urol ; 73(4): 274-280, 2020 May.
Artigo em Espanhol | MEDLINE | ID: mdl-32379062

RESUMO

OBJECTIVE: To characterize the clinical condition, the type of therapeutic approach and outcome of patients with severe renal trauma (AAST: 4 and 5) treated in a tertiary hospital. Cali, Colombia. METHODS: A descriptive observational study was conducted with patients older than 15 years treated between January 1, 2015 and January 1, 2019, with a diagnosis of renal trauma and renal vessel trauma. Demographic, clinical and trauma severity variables were collected. A univariate analysis was carried out with frequency tables, measures of central tendency, depending on type of intervention, associated lesions, use of blood products and severity indices. RESULTS: 71 medical records were analyzed, 82% male, the average age was 25 years (range: 15-55). Regarding renal traumatic grade, 69% of the patients were grade IV and 31% grade V. Penetrating injuries were seen in 87% versus 13% of injuries due to blunt (non-penetrating) mechanism. 54% of the patients weres cored with a trauma severity index >= 25 and 51% of the patients had an abdominal trauma index <= 24. Surgical management was managed in 67% vs. 32% for non-trauma management surgical. The hospital stay was 17 days on average and 16.9% had complications. CONCLUSIONS: Severe renal trauma is a frequent clinical condition in male patients between the second and third decade of life, in our environment the majority corresponds to penetrating traumas. Most cases were managed with some surgical procedure, however, with asignificant percentage of conservative management with complication rates of less than 30%, which changes the paradigm of treatment of high-grade renal trauma.


Assuntos
Traumatismos Abdominais/diagnóstico , Traumatismos Abdominais/epidemiologia , Traumatismos Abdominais/terapia , Ferimentos não Penetrantes/terapia , Ferimentos Penetrantes/epidemiologia , Ferimentos Penetrantes/terapia , Adolescente , Adulto , Colômbia/epidemiologia , Feminino , Humanos , Rim/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Adv Clin Exp Med ; 29(5): 629-633, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32459402

RESUMO

Humoral response beyond human leukocyte antigen (HLA) is of great interest in the transplant community. We decided to summarize the data on a new antigenic target called angiotensin II type 1 receptor (AT1 receptor). Non-HLA antibodies can now be detected in routine clinical care of patients after transplantation, but their role is not fully understood. Numerous analyses showed that non-HLA response may exert a higher risk of allograft rejection and allograft loss independently of the HLA system. Non-HLA response may even have a higher rate of antibody-mediated rejection. Information regarding antigen target, as well as the pathophysiology of its antibodies and diagnostic tools, is essential for a better understanding of non-HLA humoral response. Angiotensin II type 1 receptors are the most recognized target for non-HLA antibodies. Anti-AT1R Abs (anti-angiotensin II type 1-receptor-activating antibodies) may identify renal transplant patients at higher risk of graft rejection and loss. The presence of AT1 receptor expression analyzed together with anti-AT1R Abs should be considered for better transplant immunological risk assessment. Further assessment is required for a better understanding and to create appropriate therapeutic strategies.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Rim/efeitos adversos , Rim/lesões , Receptor Tipo 1 de Angiotensina/imunologia , Feminino , Antígenos HLA/imunologia , Humanos , Rim/patologia , Masculino
13.
Chem Biol Interact ; 325: 109096, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32289291

RESUMO

BACKGROUND AND AIMS: Adriamycin nephropathy model (AN), a rodent model of nephrotic syndrome disease that was caused by the nephrotoxicity of adriamycin, has been widely used for pharmacodynamic evaluation of traditional Chinese medicine (TCM) in the treatment of kidney injury. Although some studies have clearly shown the pathological process of AN, the mechanism of kidney injury have not been systematically investigated. METHODS: The reliability of AN was evaluated by weight, urinary protein quantitation, serum biochemical and histopathological examination. Transcriptomic sequencing combined with network pharmacology were used to elucidate the molecular mechanism of AN, and cell experiment combined with real-time quantitative PCR (RT-qPCR) and was used to validate the accuracy of transcriptomic sequencing result and KEGG pathways. RESULTS: Network analysis result showed that Mapk10 and Ptgs2 played important roles in the development of adriamycin-induced kidney injury. KEGG pathway analysis showed that the mechanism of kidney injury may be related to the regulation of biosynthesis of unsaturated fatty acids, complement and coagulation cascades, PPAR signaling pathway and PI3K-AKT signaling pathway. CONCLUSION: These results provide a new insight into the deep research on the mechanism of kidney injury, and provide an experimental basis for finding drug targets for the treatment of AN.


Assuntos
Doxorrubicina/farmacologia , Rim/efeitos dos fármacos , Rim/lesões , Mapeamento de Interação de Proteínas , Transcriptoma/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Rim/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
14.
Medicine (Baltimore) ; 99(16): e19853, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32312008

RESUMO

RATIONALE: Kidney is the most frequently injured organ of the genitourinary system during trauma. Bilateral penetrating renal trauma (BPRT) is extremely rare and sporadically reported in the previous literature. Here, we reported a unique case of BPRT. PATIENT CONCERNS: A 43-year-old man, with no medical history, was accidentally penetrated by a wooden stick and presented with sharp pain in the left flank. DIAGNOSIS: Laboratory tests revealed microscopic hematuria, mildly elevated leucocyte and amylase, normal hemoglobin (145 g/L) and creatinine (1.05 mg/dl). Computed tomography demonstrated bilateral penetrating renal injuries with perinephric/subcapsular hematoma, fracture of the second lumbar vertebra and 10th rib. INTERVENTIONS: An emergency exploratory laparotomy was executed immediately. According to the American Association for the Surgery of Trauma Organ Injury Scale grading system, grade V and III injuries were considered for the left and right kidney, respectively. Nephrectomy and renorrhaphy were performed on the left and right kidney, respectively. OUTCOMES: The postoperative course was uneventful. Eleven days after the surgery, the patient discharged with no complications. LESSONS: We present a rare and challenging case which was handled successfully, and it may provide useful information for the management of BPRT.


Assuntos
Dor no Flanco/etiologia , Rim/lesões , Ferimentos Penetrantes/complicações , Adulto , Dor no Flanco/diagnóstico , Hematoma , Hematúria/diagnóstico , Humanos , Rim/diagnóstico por imagem , Rim/patologia , Laparotomia/métodos , Masculino , Nefrectomia/métodos , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Ferimentos e Lesões/complicações , Ferimentos Penetrantes/diagnóstico por imagem , Ferimentos Penetrantes/patologia
15.
Adv Exp Med Biol ; 1238: 93-106, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32323182

RESUMO

Renal injury, especially chronic kidney disease (CKD), is closely associated with gut microbiota. It is well known that renal injury development could cause enteric microbial compositional disruption. On the other hand, gut microbial composition, as well as their function, would directly influence the renal disease progression. Here, in the present chapter, we will summarize the crosstalk between intestinal microbiota and renal disease and discuss some potential therapeutic approaches based on this topic.


Assuntos
Microbioma Gastrointestinal , Rim/lesões , Insuficiência Renal Crônica/patologia , Progressão da Doença , Humanos
16.
Food Chem ; 319: 126368, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-32155537

RESUMO

Maillard reaction products (MRPs), produced in the heating of food, might pose adverse effects on human health. As a classical MRP, the toxicity of furosine in kidney tissue was evaluated and the related mechanism was investigated here. We detected the concentration of furosine in mouse serum and organs using ultra-high-performance liquid chromatography, and screened out phosphatidylethanolamine (PE; 18:0/16:1) as the special metabolite in kidney by metabonomics analysis. Furthermore, furosine was verified to induce ferroptosis in kidney cells by quantitative real-time RT-PCR (q-PCR) and western blotting. The affinity between furosine and aldose reductase (AR) was measured by surface plasmon resonance (SPR), indicating AR is one of the targets of furosine. In addition, the furan ring was shown to be the main active group via structure-activity relationship (SAR) studies of furosine and other MRPs, which were toxic to kidney cells by activating ferroptosis pathway.


Assuntos
Furanos/química , Produtos Finais de Glicação Avançada/metabolismo , Rim/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Ferroptose , Produtos Finais de Glicação Avançada/química , Rim/lesões , Lisina/análogos & derivados , Lisina/metabolismo , Reação de Maillard , Camundongos , Camundongos Endogâmicos ICR
17.
Nat Rev Rheumatol ; 16(5): 255-267, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32203285

RESUMO

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus that can lead to irreversible renal impairment. Although the prognosis of LN has improved substantially over the past 50 years, outcomes have plateaued in the USA in the past 20 years as immunosuppressive therapies have failed to reverse disease in more than half of treated patients. This failure might reflect disease complexity and heterogeneity, as well as social and economic barriers to health-care access that can delay intervention until after damage has already occurred. LN progression is still poorly understood and involves multiple cell types and both immune and non-immune mechanisms. Single-cell analysis of intrinsic renal cells and infiltrating cells from patients with LN is a new approach that will help to define the pathways of renal injury at a cellular level. Although many new immune-modulating therapies are being tested in the clinic, the development of therapies to improve regeneration of the injured kidney and to prevent fibrosis requires a better understanding of the mechanisms of LN progression. This mechanistic understanding, together with the development of clinical measures to evaluate risk and detect early disease and better access to expert health-care providers, should improve outcomes for patients with LN.


Assuntos
Rim/citologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/complicações , Biomarcadores/análise , Ensaios Clínicos como Assunto , Progressão da Doença , Diagnóstico Precoce , Fibrose/prevenção & controle , Acesso aos Serviços de Saúde/estatística & dados numéricos , Humanos , Imunossupressores/uso terapêutico , Rim/lesões , Rim/metabolismo , Rim/patologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/prevenção & controle , Lúpus Eritematoso Sistêmico/epidemiologia , Nefrite Lúpica/genética , Nefrite Lúpica/imunologia , Prognóstico , Regeneração/efeitos dos fármacos , Regeneração/fisiologia , Fatores Socioeconômicos , Estados Unidos/epidemiologia
18.
Can Assoc Radiol J ; 71(3): 352-361, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32166970

RESUMO

This review aims to examine the challenges facing radiologists interpreting trauma computed tomography (CT) images in this era of a changing approach to management of solid organ trauma. After reviewing the pearls and pitfalls of CT imaging protocols for detection of traumatic solid organ injuries, we describe the key changes in the 2018 American Association for the Surgery of Trauma Organ Injury Scales for liver, spleen, and kidney and their implications for management strategies. We then focus on the important imaging findings in observed in patients who undergo nonoperative management and patients who are imaged post damage control surgery.


Assuntos
Rim/lesões , Fígado/diagnóstico por imagem , Fígado/lesões , Baço/diagnóstico por imagem , Baço/lesões , Tomografia Computadorizada por Raios X/métodos , Humanos , Rim/diagnóstico por imagem , Rim/cirurgia , Fígado/cirurgia , Baço/cirurgia , Índices de Gravidade do Trauma
19.
Adv Pharmacol ; 87: 257-276, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32089235

RESUMO

Ganoderma lucidum (G. lucidum, Lingzhi) is a well-known Chinese traditional medicine to improve health and to treat numerous diseases for over 2000 years in Asian countries. G. lucidum has the abundant chemical components such as triterpenes and polysaccharides, which have various biological activities including anti-oxidation, anti-inflammation, anti-liver disorders, anti-tumor growth and metastasis, etc. Recently, many lines of studies have elucidated the therapeutic effects of G. lucidum and its extractions on various acute kidney injury (AKI) and chronic kidney disease (CKD) pathogenesis, including autosomal dominant polycystic kidney disease, diabetic nephropathy, renal proximal tubular cell oxidative damage and fibrotic process, renal ischemia reperfusion injury, cisplatin-induced renal injury, adriamycin-induced nephropathy, chronic proteinuric renal diseases, etc. Clinical researches also showed potent anti-renal disease bioactivities of G. lucidum. In this chapter, we review experimental and clinical researches and provide comprehensive insights into the renoprotective effects of G. lucidum. In recent years, renal diseases have gradually aroused attention on account of their booming prevalence worldwide and lack of effective therapies. Although the complicated pathogenesis of kidney diseases, such as acute kidney injury (AKI) and chronic kidney diseases (CKD) have been intensively studied. The morbidity and mortality of AKI and CKD still rise continuously. Thanks to the conventional experience and the multi-target characteristics, natural products have been increasingly recognized as an alternative source for treating renal diseases.


Assuntos
Nefropatias/tratamento farmacológico , Nefropatias/prevenção & controle , Rim/lesões , Reishi/química , Produtos Biológicos/uso terapêutico , Ensaios Clínicos como Assunto , Humanos , Rim/patologia , Nefropatias/induzido quimicamente , Polissacarídeos/uso terapêutico
20.
Clin Sci (Lond) ; 134(4): 403-417, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32095833

RESUMO

Diabetic kidney disease is one of the most serious complications of diabetes worldwide and is the leading cause of end-stage renal disease. While research has primarily focused on hyperglycemia as a key player in the pathophysiology of diabetic complications, recently, increasing evidence have underlined the role of adipose inflammation in modulating the development and/or progression of diabetic kidney disease. This review focuses on how adipose inflammation contribute to diabetic kidney disease. Furthermore, it discusses in detail the underlying mechanisms of adipose inflammation, including pro-inflammatory cytokines, oxidative stress, and AMPK/mTOR signaling pathway and critically describes their role in diabetic kidney disease. This in-depth understanding of adipose inflammation and its impact on diabetic kidney disease highlights the need for novel interventions in the treatment of diabetic complications.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/patologia , Inflamação/patologia , Rim/lesões , NADPH Oxidase 4/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Humanos
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