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1.
Am J Pathol ; 190(4): 799-816, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32220420

RESUMEN

Roundabout guidance receptor 2 (ROBO2) plays an important role during early kidney development. ROBO2 is expressed in podocytes, inhibits nephrin-induced actin polymerization, down-regulates nonmuscle myosin IIA activity, and destabilizes kidney podocyte adhesion. However, the role of ROBO2 during kidney injury, particularly in mature podocytes, is not known. Herein, we report that loss of ROBO2 in podocytes [Robo2 conditional knockout (cKO) mouse] is protective from glomerular injuries. Ultrastructural analysis reveals that Robo2 cKO mice display less foot process effacement and better-preserved slit-diaphragm density compared with wild-type littermates injured by either protamine sulfate or nephrotoxic serum (NTS). The Robo2 cKO mice also develop less proteinuria after NTS injury. Further studies reveal that ROBO2 expression in podocytes is up-regulated after glomerular injury because its expression levels are higher in the glomeruli of NTS injured mice and passive Heymann membranous nephropathy rats. Moreover, the amount of ROBO2 in the glomeruli is also elevated in patients with membranous nephropathy. Finally, overexpression of ROBO2 in cultured mouse podocytes compromises cell adhesion. Taken together, these findings suggest that kidney injury increases glomerular ROBO2 expression that might compromise podocyte adhesion and, thus, loss of Robo2 in podocytes could protect from glomerular injury by enhancing podocyte adhesion that helps maintain foot process structure. Our findings also suggest that ROBO2 is a therapeutic target for podocyte injury and podocytopathy.


Asunto(s)
Enfermedades Renales/prevención & control , Glomérulos Renales/citología , Podocitos/citología , Sustancias Protectoras/metabolismo , Receptores Inmunológicos/deficiencia , Adulto , Animales , Femenino , Humanos , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Glomérulos Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Podocitos/metabolismo , Proteinuria/metabolismo , Proteinuria/patología , Proteinuria/prevención & control , Ratas
2.
Acta Cir Bras ; 34(12): e201901201, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32022101

RESUMEN

PURPOSE: To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, able to modulate the histological changes caused by the NASID (meloxicam). METHODS: Wistar rats were assigned into three groups (n=6 rats/group): Sham group (saline solution), NSAID group (meloxicam - 15 mg/kg) and Rut-bpy group (100 mg/kg of Rut-bpy associated with 15mg/kg of meloxicam). At the end of experiments, kidneys were removed for histological study, fractal dimension and lacunarity in all animals. RESULTS: At the histological examination, all animals (six animals - 100 %) in the NSAID group had membrane thickening and other changes (necrosis, acute tubular congestion and vascular congestion); on the other hand, only one animal (16.6 %) of the Rut-bpy group had congestion. The fractal dimension and lacunarity were greater in the control and Rut-bpy group than in NSAIDs group (p<0.05). CONCLUSION: Rut-bpy may prevent renal histological changes in rats caused by meloxicam.


Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Renales/inducido químicamente , Enfermedades Renales/prevención & control , Meloxicam/efectos adversos , Donantes de Óxido Nítrico/farmacología , Compuestos Organometálicos/farmacología , Rutenio/farmacología , 2,2'-Dipiridil/análogos & derivados , Animales , Fractales , Enfermedades Renales/patología , Masculino , Distribución Aleatoria , Ratas Wistar , Reproducibilidad de los Resultados
3.
Medicine (Baltimore) ; 99(3): e18798, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32011483

RESUMEN

RATIONALE: Renal hemosiderosis is a disease in which hemosiderin deposits in the renal cortex as a form of iron overload. However, cases of renal hemosiderosis due to intravascular hemolysis following mitral valve repair have been rarely reported. PATIENT CONCERNS: We present the case of a 62-year-old woman who developed asymptomatic urinary abnormalities including microscopic hematuria and proteinuria due to renal hemosiderosis following a mitral valve repair surgery performed two years earlier. DIAGNOSES: A percutaneous renal biopsy showed no specific glomerular abnormality, tubular atrophy, or interstitial fibrosis but extensive deposition of hemosiderin in the proximal tubule. The patient was diagnosed with renal hemosiderosis and chronic intravascular hemolysis following mitral valve repair. INTERVENTIONS: Our patient refused a mitral valve repeat surgery and hence was treated with oral iron preparations, N-acetylcysteine, and a ß-receptor blocker. OUTCOMES: Moderate mitral regurgitation with the regurgitant blood striking against the annuloplasty ring was confirmed on follow-up echocardiography. After the 24-month follow-up period, hemolytic anemia persisted, but there was no significant decline of renal function. LESSONS: For cases of chronic intravascular hemolysis accompanied with asymptomatic urinary abnormalities, a renal biopsy is required to exclude underlying kidney pathology and predict potential renal insufficiency.


Asunto(s)
Implantación de Prótesis de Válvulas Cardíacas , Hemólisis , Hemosiderosis/diagnóstico , Enfermedades Renales/diagnóstico , Complicaciones Posoperatorias/diagnóstico , Femenino , Hemosiderosis/etiología , Hemosiderosis/patología , Humanos , Enfermedades Renales/etiología , Enfermedades Renales/patología , Persona de Mediana Edad , Insuficiencia de la Válvula Mitral/cirugía , Complicaciones Posoperatorias/patología
4.
Vet Clin North Am Equine Pract ; 36(1): 121-134, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32037140

RESUMEN

Clinicopathologic evaluation of renal function and renal disease in sick adult horses remains grounded in detection of azotemia, assessment of serum and urine electrolyte concentrations, and evaluation of urinalysis findings, including specific gravity, reagent strip analysis, and sediment examination. Because increases in serum or plasma urea nitrogen and creatinine concentrations are insensitive indicators of a decreased glomerular filtration rate, there is considerable interest in identifying novel biomarkers of renal function or injury in blood and urine, with serum symmetric dimethylarginine concentration being the most recent addition to the commercial market.


Asunto(s)
Enfermedades de los Caballos/patología , Enfermedades de los Caballos/orina , Enfermedades Renales/veterinaria , Animales , Biomarcadores/sangre , Biomarcadores/orina , Enfermedades de los Caballos/sangre , Caballos , Enfermedades Renales/patología , Enfermedades Renales/orina , Masculino , Urinálisis/veterinaria
5.
Ecotoxicol Environ Saf ; 192: 110256, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32014724

RESUMEN

The modulatory role of the Spirulina platensis (SP) against furan-induced (FU) hepatic and renal damage was assessed in this study. For achieving this, sixty rats were distributed into six groups: control group, SP-administered group (300 mg/kg b.wt orally for 28 days), a FU-intoxicated group (16 mg/kg b.wt, orally, daily for 28 days), protective co-treated group SP/F (administered SP 300 mg/kg b.wt, one week before, and concurrently with FU intoxication), therapeutic co-treated group FU/SP (administered SP 300 mg/kg b.wt, one week after FU intoxication for 28 days) and protective/therapeutic co-treated group SP/FU/SP (administered SP one week before and after, concurrently with FU intoxication). Subsequently, the biochemical responses and the histology of hepatic and renal tissues in treated rats were assessed. The results indicated that FU intoxication induced a significant hepato- and nephropathy represented by the elevation in the values of tissue injury biomarkers and reduction in protein levels. Histologically, a wide range of morphological, cytotoxic, inflammatory, and vascular alterations as well as downregulation in the immunoexpression of the proliferating cell nuclear antigen (PCNA) and the proliferation-associated nuclear antigen (Ki-67) were induced by FU intoxication. Oral SP administration, particularly in the protective/therapeutic co-treated group, markedly supressed the serum levels of the tissue injury biomarkers, diminished the inflammatory response, restored the cytotoxic alterations, upregulated the immunoexpression of PCNA and Ki-67, and restored the perturbed morphology of the hepatic and renal tissues. In conclusion, the obtained data demonstrated that SP co-administration elicits both protective and therapeutic potential against the FU-induced hepato- and nephropathy.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/terapia , Furanos/toxicidad , Enfermedades Renales/terapia , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Spirulina , Animales , Biomarcadores/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Antígeno Ki-67/metabolismo , Riñón/metabolismo , Riñón/patología , Riñón/ultraestructura , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Hígado/metabolismo , Hígado/patología , Hígado/ultraestructura , Masculino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratas
6.
Phytomedicine ; 67: 153163, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31901891

RESUMEN

BACKGROUND: Renal interstitial fibrosis is a common pathway through which chronic kidney disease progresses to end-stage renal disease. There are currently no effective drugs available to treat kidney fibrosis, so traditional medicine is likely to be a candidate. The therapeutic potential of saikosaponin B2 (SSB2), a biologically active ingredient of Radix Bupleuri, on renal fibrosis has not been reported. METHODS: A unilateral ureteral obstruction (UUO) model was conducted to induce renal interstitial fibrosis in mice. SSB2's effect was valuated by histological staining and exploring the changes in expression of relative proteins and mRNAs. A conditional medium containing sonic hedgehog variant protein stimulating normal rat kidney interstitial fibroblast cells (NRK-49F) was used in an in vitro model to determine the possible mechanism. The molecular target of SSB2 was verified using several mutation plasmids. RESULTS: SSB2 administration reduced kidney injury and alleviated interstitial fibrosis by decreasing excessive accumulation of extracellular matrix components in UUO mice. It could also reduce the expression of α-SMA, fibronectin and Gli1, a crucial molecule of the hedgehog (Hh) signaling pathway both in vivo and in vitro. In NIH-3T3 cells simulated by conditional medium containing sonic hedgehog variant protein, SSB2 showed the ability to decrease the expression of Gli1 and Ptch1 mRNA. Using a dual-luciferase reporter assay, SSB2 suppressed the Gli-luciferase reporter activity in NIH-3T3 cells, and the IC50 was 0.49 µM, but had no effect on the TNF-α/NF-κB and Wnt/ß-catenin signaling pathways, indicating the inhibition selectivity on the Hh signaling pathway. Furthermore, SSB2 failed to inhibit the Hh pathway activity evoked by ectopic expression of Gli2ΔN and Smo D473H, suggesting that SSB2 might potentially act on smoothened receptors. CONCLUSION: SSB2 could attenuate renal fibrosis and decrease fibroblast activation by inhibiting the Hh signaling pathway.


Asunto(s)
Proteínas Hedgehog/metabolismo , Enfermedades Renales/tratamiento farmacológico , Riñón/efectos de los fármacos , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Animales , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibrosis , Células HEK293 , Humanos , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Células 3T3 NIH , Ácido Oleanólico/farmacología , Ratas , Transducción de Señal/efectos de los fármacos , Receptor Smoothened/metabolismo , Proteína Gli2 con Dedos de Zinc/genética , Proteína Gli2 con Dedos de Zinc/metabolismo
7.
Cell Physiol Biochem ; 54(1): 88-109, 2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-31990489

RESUMEN

Extracellular vesicles (EVs) are important mediators of intercellular communication. Since EVs are also released during pathological conditions, there has been considerable interest in their potential as sensitive biomarkers of cellular stress and/or injury. In the context of kidney disease, urinary EVs are promising indicators of glomerular and tubular damage. In the present review we discuss the role of urinary EVs in kidney health and disease. Our focus is to explore urinary large EVs (lEVs, often referred to as microparticles or microvesicles) as direct and noninvasive early biomarkers of renal injury. In this regard, studies have been demonstrating altered levels of urinary lEVs, especially podocyte-derived lEVs, preceding the decrease of renal function assessed by classical markers. In addition, we discuss the role of small EVs (sEVs, often referred to as exosomes) and their contents in kidney pathophysiology. Even though results concerning the production of sEVs during diseased conditions are varied, there has been a consensus on the importance of urinary sEV content assessment in kidney disease. These mediators, including EV-released miRNAs and mRNAs, are responsible for EV-mediated signaling in the regulation of renal cellular homeostasis, pathogenesis and regeneration. Finally, steps necessary for the validation of EVs as reliable markers will be discussed.


Asunto(s)
Vesículas Extracelulares/patología , Enfermedades Renales/diagnóstico , Glomérulos Renales/patología , Túbulos Renales/patología , Animales , Biomarcadores/análisis , Biomarcadores/orina , Humanos , Enfermedades Renales/patología , Enfermedades Renales/orina
8.
J Vasc Access ; 21(1): 73-78, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31204556

RESUMEN

BACKGROUND: Percutaneous renal biopsy can result in serious complications. The study is aimed to compare the safety and yield between the two approaches of biopsy techniques: the conventional craniocaudal and the caudocranial trajectory of the biopsy needle under real-time ultrasound guidance. METHODS: In this prospective observational study, a total of 80 serial kidney biopsies were performed, 40 with craniocaudal angulation and 40 with caudocranial angulation of the biopsy needle on the random allocation of 1:1 in each group. In the craniocaudal approach, the patient must hold the breath in deep inspiration to make a lower pole of the kidney approachable during unloading the biopsy gun, which was not required in caudocranial trajectory as the lower pole was approachable without holding the breath in deep inspiration. All kidney biopsies were performed percutaneously under real-time ultrasonogram guidance with a 16-cm-long, 16- or 18-gauge needles with a penetration depth of 22 mm and a sample notch of 18 mm. The yield and complications between the two groups were analyzed. RESULTS: Both the groups were comparable in essential demographic characteristics. The study found that the caudocranial position of renal biopsy is equally suitable concerning tissue yield without any increase in the risk of complications and a smaller number of passes to obtain adequate tissue. CONCLUSION: Caudocranial trajectory of the biopsy needle using a probe needle guide is as safe as the craniocaudal approach. Both approaches have similar yield and complications; however, the caudocranial approach provides ease to the patient during the procedure.


Asunto(s)
Biopsia con Aguja , Biopsia Guiada por Imagen/métodos , Enfermedades Renales/patología , Riñón/patología , Ultrasonografía Intervencional , Adolescente , Adulto , Anciano , Biopsia con Aguja/instrumentación , Niño , Diseño de Equipo , Femenino , Humanos , Biopsia Guiada por Imagen/efectos adversos , Biopsia Guiada por Imagen/instrumentación , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Agujas , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Adulto Joven
9.
Life Sci ; 241: 117109, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31786195

RESUMEN

AIMS: This study aimed to identify interstitial molecules that were responsible for the deterioration of the esiantimated glomerular filtration rate (eGFR) in diabetic nephropathy (DN). MATERIALS AND METHODS: Weighted gene co-expression network analysis (WGCNA) was used to link the tubulointerstitial gene expression profile of DN to eGFR values. The relationship of eGFR with each sub-domain regulator in the network was analyzed with the linear regression model. Gene sets enrichment analysis (GSEA) was applied to detect the molecular changes mostly relating to the essential regulators. KEY FINDINGS: Four co-expression modules were found strongly correlating with eGFR values. Genes from these modules were over-represented in fibrosis-related biological processes (extracellular matrix (ECM) organization and cell adhesion) and pathways (integrin signaling and ECM-receptor interaction). Of sub-domains in the gene interaction network, the expression of hypoxia-inducible factor 1A (HIF1A) was most negatively correlated with eGFR (R2 = 0.417, P = 0.026). The positive correlations between HIF1A and its target genes were found, indicating an enhanced transcriptional activity of HIF1A. We also found that HIF1A positively correlated with CCAAT enhancer binding protein delta (CEBPD) (r = 0.731, P = 0.011), an activator of HIF1A transcription. Moreover, GSEA showed that samples with high HIF1A expression were enriched with fibrosis associated signaling, like ECM-receptor interaction and cell adhesion. Intriguingly, vascular epithelial growth factor A (VEGFA) expression decreased while HIF1A increased (R2 = 0.733, P = 0.001), suggesting VEGFA loss may exacerbate hypoxia and stimulate HIF1A induction. SIGNIFICANCE: The present study suggested that interstitial HIF1A may be involved in renal interstitial fibrosis in DN.


Asunto(s)
Nefropatías Diabéticas/genética , Fibrosis/fisiopatología , Tasa de Filtración Glomerular/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Riñón/patología , Adulto , Anciano , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/fisiopatología , Femenino , Fibrosis/genética , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Tasa de Filtración Glomerular/fisiología , Humanos , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular/genética
10.
Toxicol Lett ; 319: 204-212, 2020 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-31760061

RESUMEN

Doxorubicin has been indicated to be cardiotoxic and nephrotoxic, and thus it is often used as a model drug. Possible molecular mechanisms of this toxicity have been proposed, however, the systematic investigation of time-related metabolic trajectories specific to renal toxicity has rarely been reported. The present study was designed to assess time-dependent changes in doxorubicin-induced nephropathy through urinary metabolomics and to reveal the molecular mechanism based on key pathways. Urinary metabolomics revealed that the 14th day was the critical time point for model construction. Pathway analysis results showed that 5 pathways with impact (>0.1), FDR (<0.1) and p value (<0.05) were important. Furthermore, three pathways, including butanoate metabolism, alanine, aspartate and glutamate metabolism and arginine and proline metabolism, were focused on and validated by partial least squares regression analysis (PLS-RA) and molecular docking techniques. Our findings also showed that robust metabolomics combined with PLS-RA and molecular docking techniques is promising for elucidating time-dependent changes due to doxorubicin toxicity and for clarifying mechanisms, and the results provide a research foundation for the construction of a nephropathy model.


Asunto(s)
Antibióticos Antineoplásicos/toxicidad , Doxorrubicina/toxicidad , Enfermedades Renales/inducido químicamente , Enfermedades Renales/orina , Metaboloma/efectos de los fármacos , Aminoácidos/metabolismo , Animales , Riñón/patología , Enfermedades Renales/patología , Masculino , Metabolómica , Simulación del Acoplamiento Molecular , Proteinuria/inducido químicamente , Ratas , Ratas Sprague-Dawley , Factores de Tiempo
11.
Life Sci ; 241: 117187, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31863776

RESUMEN

AIMS: Renal interstitial fibrosis (RIF) is marked by the epithelial-mesenchymal transition (EMT) and excessive extracellular matrix deposition. The long noncoding RNA myocardial infarction-associated transcript (MIAT) facilitates RIF; however, the molecular mechanism of MIAT in RIF remains unclear. Here, we explored the possible underlying mechanisms through which MIAT modulates RIF. MATERIALS AND METHODS: MIAT expression in human renal fibrotic tissues and unilateral ureteral obstruction (UUO) model mice was detected by qPCR. Transforming growth factor ß1 (TGF-ß1) was introduced to stimulate the EMT in human renal proximal tubular epithelial (HK-2) cells. CCK8, EdU, transwell and wound healing assays were employed to measure cell viability, proliferation, and migration respectively. RNA immunoprecipitation (RIP) assays and dual luciferase reporter assays were applied to determine the relationships among MIAT, miR-145, and EIF5A2. KEY FINDINGS: MIAT was upregulated in human renal fibrotic tissues and UUO model mice compared with normal tissue adjacent to renal tumors and sham operation mice, respectively. MIAT knockdown reduced cell viability, proliferation, migration, and the EMT in HK-2 cells. Additionally, MIAT served as an endogenous sponge for miR-145 in the TGF-ß1-induced-EMT in HK-2 cells, as demonstrated by dual luciferase reporter assays and RIP assays. EIF5A2 was confirmed as a target of miR-145, and MIAT knockdown suppressed EIF5A2 expression by sponging miR-145. Downregulation of EIF5A2 partly reversed induction of the EMT by miR-145 inhibitor transfection. SIGNIFICANCE: MIAT promoted cell viability, proliferation, migration, and the EMT via regulation of the miR-145/EIF5A2 axis. These data established a potential therapy for RIF.


Asunto(s)
Transición Epitelial-Mesenquimal , Fibrosis/patología , Enfermedades Renales/patología , MicroARNs/genética , Factores de Iniciación de Péptidos/metabolismo , ARN Largo no Codificante/genética , Proteínas de Unión al ARN/metabolismo , Obstrucción Ureteral/patología , Animales , Estudios de Casos y Controles , Fibrosis/genética , Fibrosis/metabolismo , Regulación de la Expresión Génica , Humanos , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Factores de Iniciación de Péptidos/genética , Proteínas de Unión al ARN/genética , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/genética , Obstrucción Ureteral/metabolismo
12.
Int Braz J Urol ; 46(1): 15-25, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31851454

RESUMEN

Sarcoidosis is a multisystem granulomatous disease characterized by epithelioid noncaseating granulomas associated with clinical and radiologic findings. The cause of this disease is still uncertain. Sarcoidosis affects mostly lungs and lymph nodes and is not usually considered a urological disease, therefore, this etiology may be overlooked in several urological disorders, such as hypercalcemia, hypercalciuria and nephrolithiasis. It affects all races and genders. This review aims to describe the urological manifestations of sarcoidosis and to elucidate how the disease may affect the management of numerous urological conditions.


Asunto(s)
Enfermedades Renales/patología , Sarcoidosis/patología , Biopsia , Enfermedad Crónica , Humanos , Hipercalcemia/diagnóstico , Hipercalcemia/patología , Hipercalciuria/diagnóstico , Hipercalciuria/patología , Enfermedades Renales/diagnóstico , Enfermedades Renales/terapia , Sarcoidosis/diagnóstico , Sarcoidosis/terapia
13.
Chem Biol Interact ; 316: 108926, 2020 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-31874164

RESUMEN

Grape seed proanthocyanidin extract (GSPE) has been reported to exhibit a variety of protective effects, such as antioxidant, anti-atherosclerosis and other pharmacological effects. As a member of the complement system, complement component 3 (C3) deposition in the glomerulus is recognized as an important causative mediator of various kidney diseases. In this study, we aimed to identify the effect of GSPE on C3 in the chronic kidney fibrosis and evaluate the possible mechanism. We observed that administration of GSPE relieves inflammation and chronic renal fibrosis in mouse models of UUO. GSPE inhibited C3 secreted by macrophages to relieve renal interstitial inflammation. In vitro, we found that C3 stimulated HMGB1 translocation form nucleus to cytoplasm and promote the expression of pro-inflammatory cytokines including TGF-ß1 in primary renal tubular epithelial cells (PTEC), which could be inhibited by GSPE. Meanwhile, GSPE could also decreased HMGB1-induced EMT of PTEC through suppresses the HMGB1/TLR4/p65/TGF-ß1 pathway. In addition, the myofibroblast activation was inhibited by GSPE via TGF-ß1/Smad2/3 signaling pathways in normal rat kidney fibroblast (NRK-49F) cells. Overall, these observations provide that GSPE alleviates renal fibrosis by inhibiting the C3/HMGB1/TGF-ß1 pathway and could thus lead to find the potential therapy for the suppression of renal fibrosis.


Asunto(s)
Extracto de Semillas de Uva/farmacología , Riñón/efectos de los fármacos , Proantocianidinas/farmacología , Transducción de Señal/efectos de los fármacos , Animales , Células Cultivadas , Complemento C3/metabolismo , Modelos Animales de Enfermedad , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibrosis , Extracto de Semillas de Uva/uso terapéutico , Proteína HMGB1/metabolismo , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Enfermedades Renales/prevención & control , Túbulos Renales/citología , Masculino , Ratones , Ratones Endogámicos C57BL , Proantocianidinas/uso terapéutico , Ratas , Factor de Crecimiento Transformador beta1/metabolismo
14.
BMC Pregnancy Childbirth ; 19(1): 505, 2019 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-31852454

RESUMEN

BACKGROUND: Spontaneous formation of urinoma is a rare condition, especially for pregnant women. We report a patient in the third trimester of pregnancy with a spontaneous renal rupture who then develops a urinoma from urine leaking into the perinephric space. CASE PRESENTATION: A 23-year-old primagravida was diagnosed with a spontaneous renal rupture and acute left loin pain accompanied by hematuria when she was 35 weeks pregnant. A sub-capsular perinephric cyst then developed to a size of 319 × 175 × 253 mm, and because of discomfort to the patient, we performed Cesarean section. After a healthy male newborn was delivered, fluid was suctioned from a large perirenal cyst that had an estimated size of 300 × 200 × 300 mm. A percutaneous nephrostomy tube was left in the cyst until CT showed no remaining fluid. In the six-month follow-up, the patient showed no perirenal extravasation according to an ultrasound scan, and the urine analysis and renal function tests were normal. CONCLUSION: Close follow-up should be recommended for the patient who has renal rupture after conservative therapy, especially for pregnant woman. CT or MRI should be considered in addition to utilizing ultrasound in the management of pregnant women who present with urinomas. Percutaneous nephrostomy is suggested as an appropriate treatment for large urinomas.


Asunto(s)
Enfermedades Renales/patología , Complicaciones del Embarazo/patología , Urinoma/patología , Cesárea , Femenino , Humanos , Recién Nacido , Enfermedades Renales/complicaciones , Nacimiento Vivo , Masculino , Embarazo , Complicaciones del Embarazo/etiología , Tercer Trimestre del Embarazo , Rotura Espontánea , Urinoma/etiología , Adulto Joven
15.
Int J Mol Sci ; 21(1)2019 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-31877774

RESUMEN

In order to effectively develop personalized medicine for kidney diseases we urgently need to develop highly accurate biomarkers for use in the clinic, since current biomarkers of kidney damage (changes in serum creatinine and/or urine albumin excretion) apply to a later stage of disease, lack accuracy, and are not connected with molecular pathophysiology. Analysis of urine peptide content (urinary peptidomics) has emerged as one of the most attractive areas in disease biomarker discovery. Urinary peptidome analysis allows the detection of short and long-term physiological or pathological changes occurring within the kidney. Urinary peptidomics has been applied extensively for several years now in renal patients, and may greatly improve kidney disease management by supporting earlier and more accurate detection, prognostic assessment, and prediction of response to treatment. It also promises better understanding of kidney disease pathophysiology, and has been proposed as a "liquid biopsy" to discriminate various types of renal disorders. Furthermore, proteins being the major drug targets, peptidome analysis may allow one to evaluate the effects of therapies at the protein signaling pathway level. We here review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases.


Asunto(s)
Enfermedades Renales/orina , Péptidos/orina , Proteómica/métodos , Biomarcadores/química , Biomarcadores/orina , Humanos , Enfermedades Renales/patología , Espectrometría de Masas/métodos , Péptidos/química , Medicina de Precisión/métodos , Urinálisis/métodos
17.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(9): 710-727, nov. 2019. ilus, tab
Artículo en Español | IBECS | ID: ibc-185563

RESUMEN

La piel es el órgano más extenso y más expuesto del cuerpo humano. Ello implica un magnífico terreno para el diagnóstico precoz de las enfermedades sistémicas que cursan con afectación sistémica y para las cuales la piel se vuelve un marcador diagnóstico. Las bases conceptuales y los criterios diagnósticos de muchas de estas entidades se han visto modificados o ampliados en los últimos años, con lo que la aproximación a la biopsia cutánea y la evaluación de los signos dermatopatológicos útiles en el diagnóstico precoz han variado también. En esta revisión intentamos hacer un enfoque de algunos de los procesos sistémicos con repercusión cutánea que más han variado conceptualmente en las últimas décadas


The skin is the largest and most exposed organ in the human body and the ideal place to look for signs that aid in the early diagnosis of systemic diseases with cutaneous effects. As the concepts that underpin our understanding of many of these diseases have evolved or expanded in recent years, there have also been changes in the criteria we use for early diagnosis, including our approaches to skin biopsy and dermatopathologic evaluation. This review focuses on some of the systemic processes with skin manifestations for which our basic understanding has changed most in recent decades


Asunto(s)
Humanos , Enfermedades Autoinflamatorias Hereditarias/diagnóstico , Diagnóstico Precoz , Tejido Subcutáneo/patología , Enfermedad Relacionada con Inmunoglobulina G4/patología , Biopsia , Enfermedades Autoinflamatorias Hereditarias/patología , Síndrome de Behçet/patología , Piodermia Gangrenosa/patología , Artritis Juvenil/complicaciones , Exantema , Diagnóstico Diferencial , Linfadenitis Necrotizante Histiocítica/complicaciones , Enfermedades Renales/patología
18.
Toxicol Lett ; 317: 110-119, 2019 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-31618666

RESUMEN

Trichloroethylene (TCE), a commonly used industrial solvent and degreasing agent, is known to cause trichloroethylene hypersensitivity syndrome (THS) with multi-system damage, including skin, liver and kidney. Clinical evidence have shown that the kidney injury occurs in THS and our previous studies suggested that the terminal complement complex C5b-9 deposited in impaired renal tubules induced by TCE with unclear mechanisms. In the present study, we questioned whether activation of the complement system with renal deposition of C5b-9 contributes to TCE-induced kidney injury in THS. We established a BALB/c mouse model of TCE sensitization with or without pretreatment of exogenous CD59, a C5b-9 inhibitory protein. H&E staining, PAS staining, and biochemical detection of urinary proteins were performed to assess renal function. Deposition of C5b-9 and expression of CD59 were evaluated by immunohistochemistry. Sub-lytic effects of C5b-9 in tubular epithelial cells were assessed by lactate dehydrogenase (LDH) cytotoxicity assay. Expression of endocytosis receptors megalin and cubilin on proximal tubules were assessed by immunofluorescence and qRT-PCR. We found that TCE sensitization induced structural and functional changes of renal tubules in mice, associated with the deposition of sub-lytic C5b-9 on proximal tubular epithelial cells. TCE sensitization decreased proximal tubule uptake of filtered proteins and renal expression of megalin and cubilin, phenotypes that were attenuated by pretreatment with exogenous CD59. Overall, our findings reveal a novel mechanism underlying sub-lytic C5b-9 acting on megalin and cubilin, contributes to the renal tubules damage by TCE exposure.


Asunto(s)
Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Endocitosis , Hipersensibilidad/metabolismo , Enfermedades Renales/metabolismo , Túbulos Renales Proximales/metabolismo , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Receptores de Superficie Celular/metabolismo , Tricloroetileno , Animales , Células Cultivadas , Activación de Complemento , Complejo de Ataque a Membrana del Sistema Complemento/inmunología , Modelos Animales de Enfermedad , Femenino , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Enfermedades Renales/inducido químicamente , Enfermedades Renales/inmunología , Enfermedades Renales/patología , Túbulos Renales Proximales/inmunología , Túbulos Renales Proximales/patología , Ratones Endogámicos BALB C , Transporte de Proteínas
19.
Braz J Med Biol Res ; 52(11): e8772, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31664306

RESUMEN

This study aimed to investigate the mechanism of fluorofenidone (AKF-PD) in treating renal interstitial fibrosis in rats with unilateral urinary obstruction (UUO). Thirty-two male Sprague-Dawley rats were randomly divided into sham, UUO, UUO + enalapril, and UUO + AKF-PD groups. All rats, except sham, underwent left urethral obstruction surgery to establish the animal model. Rats were sacrificed 14 days after surgery, and serum was collected for renal function examination. Kidneys were collected to observe pathological changes. Immunohistochemistry was performed to assess collagen I (Col I) protein expression, and terminal deoxynucleotidyl transferase-mediated nick end-labeling staining to observe the apoptosis of renal tubular epithelial cells. The expression of Fas-associated death domain (FADD), apoptotic protease activating factor-1 (Apaf-1), and C/EBP homologous protein (CHOP) proteins was evaluated by immunohistochemistry and western blot analysis. AKF-PD showed no significant effect on renal function in UUO rats. The pathological changes were alleviated significantly after enalapril or AKF-PD treatment, but with no significant differences between the two groups. Col I protein was overexpressed in the UUO group, which was inhibited by both enalapril and AKF-PD. The number of apoptotic renal tubular epithelial cells was much higher in the UUO group, and AKF-PD significantly inhibited epithelial cells apoptosis. The expression of FADD, Apaf-1, and CHOP proteins was significantly upregulated in the UUO group and downregulated by enalapril and AKF-PD. In conclusion, AKF-PD improved renal interstitial fibrosis by inhibiting apoptosis of renal tubular epithelial cells in rats with UUO.


Asunto(s)
Apoptosis/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Enfermedades Renales/patología , Piridonas/farmacología , Obstrucción Ureteral/patología , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Factor Apoptótico 1 Activador de Proteasas/efectos de los fármacos , Factor Apoptótico 1 Activador de Proteasas/metabolismo , Nitrógeno de la Urea Sanguínea , Colágeno Tipo I/efectos de los fármacos , Colágeno Tipo I/metabolismo , Creatinina/sangre , Modelos Animales de Enfermedad , Enalapril/metabolismo , Enalapril/farmacología , Proteína de Dominio de Muerte Asociada a Fas/efectos de los fármacos , Proteína de Dominio de Muerte Asociada a Fas/metabolismo , Fibrosis , Masculino , Piridonas/metabolismo , Distribución Aleatoria , Ratas Sprague-Dawley , Factor de Transcripción CHOP/efectos de los fármacos , Factor de Transcripción CHOP/metabolismo
20.
Transplant Proc ; 51(9): 2890-2898, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31606185

RESUMEN

BACKGROUND: Transplantation of kidneys from donation after cardiocirculatory death (DCD) donors is becoming an ever-increasing reality. So far, biopsy histologic assessment is the main parameter for evaluation of graft suitability, but it has several drawbacks and has poor reliability. The aim of this study is to verify if real-time renal resistance (RR) measurement during hypothermic machine perfusion (HMP) can be used as a reliable parameter to evaluate the quality of grafts from DCD and extracorporeal membrane oxygenation (ECMO) donors. METHODS: From January 2015 to September 2018, HMP has been systematically applied to all organs from DCD and ECMO donors. All grafts underwent preimplantation biopsy histologic assessment with Karpinski's score. Single kidney transplants (SKTs) or double kidney transplants (DKTs) were performed according to biopsy score results. Kidneys were considered suitable for transplant if RR reached ≤ 1.0 within 3 hours of perfusion. RR trend and postoperative outcome were analyzed considering biopsy score and donor type. RESULTS: A total of 30 kidneys (15 from DCD and 15 from ECMO donors) were used to perform 26 transplants (22 SKTs and 4 DKTs). Considering RR trend, all grafts were considered suitable for transplant within 1 hour of perfusion. Biopsy confirmed this result in all cases, and median score was 3 (range, 0-7). SKT score kidneys had lower starting RR than DKT ones (1.88 vs 2.88; P = .04) but identical final RR (0.58 vs 0.57; P = .76). DKT recipients had faster postoperative creatinine reduction than SKT recipients but similar postoperative day 30 value (1.42 vs 1.15 mg/dL; P = .20). No differences were found between DCD and ECMO grafts in terms of RR trend and postoperative outcome. CONCLUSIONS: HMP can be an alternative to histologic biopsy assessment for evaluation of transplant suitability of DCD and ECMO kidneys. If acceptability threshold is reached, SKT can be performed in all cases. ECMO donors should be considered like DCD donors.


Asunto(s)
Trasplante de Riñón/métodos , Obtención de Tejidos y Órganos/métodos , Trasplantes/patología , Trasplantes/provisión & distribución , Biopsia , Oxigenación por Membrana Extracorpórea/métodos , Femenino , Supervivencia de Injerto , Humanos , Enfermedades Renales/diagnóstico , Enfermedades Renales/patología , Masculino , Persona de Mediana Edad , Perfusión/métodos , Proyectos Piloto , Factores de Tiempo , Donantes de Tejidos/provisión & distribución , Trasplantes/normas
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