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Braz. j. med. biol. res ; 54(3): e9206, 2021. graf
Article in English | LILACS | ID: biblio-1153519


Renal fibrosis is one of the most significant pathological changes after ureteral obstruction. Transforming growth factor-β (TGF-β) signaling pathway plays essential roles in kidney fibrosis regulation. The aims of the present study were to investigate effects of microRNA-302b (miR-302b) on renal fibrosis, and interaction between miR-302b and TGF-β signaling pathway in murine unilateral ureteral obstruction (UUO) model. Microarray dataset GSE42716 was downloaded by retrieving Gene Expression Omnibus database. In accordance with bioinformatics analysis results, miR-302b was significantly down-regulated in UUO mouse kidney tissue and TGF-β1-treated HK-2 cells. Masson's trichrome staining showed that miR-302b mimics decreased renal fibrosis induced by UUO. The increased mRNA expression of collagen I and α-smooth muscle actin (α-SMA) and decreased expression of E-cadherin were reversed by miR-302b mimics. In addition, miR-302b up-regulation also inhibited TGF-β1-induced epithelial mesenchymal transition (EMT) of HK-2 cells by restoring E-cadherin expression and decreasing α-SMA expression. miR-302b mimics suppressed both luciferase activity and protein expression of TGF-βR2. However, miR-302b inhibitor increased TGF-βR2 luciferase activity and protein expression. Meanwhile, miR-302b mimics inhibited TGF-βR2 mRNA expression and decreased Smad2 and Smad3 phosphorylation in vivo and in vitro. Furthermore, over-expression of TGF-βR2 restored the miR-302b-induced decrease of collagen I and α-SMA expression. In conclusion, this study demonstrated that miR-302b attenuated renal fibrosis by targeting TGF-βR2 to suppress TGF-β/Smad signaling activation. Our findings showed that elevating renal miR-302b levels may be a novel therapeutic strategy for preventing renal fibrosis.

Humans , Animals , Rats , Ureteral Obstruction/pathology , Signal Transduction , Transforming Growth Factor beta/metabolism , MicroRNAs/genetics , Smad Proteins , Kidney Diseases/genetics , Fibrosis , Cell Line , Epithelial-Mesenchymal Transition , Kidney/pathology , Kidney Diseases/pathology
Pesqui. vet. bras ; 40(12): 1002-1009, Dec. 2020. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1155035


Chronic kidney disease (CKD) is characterized by irreversible morphostructural lesions that can progressively evolve to chronic renal insufficiency and kidney failure. It is known that the heart and kidneys are closely related, and that communication between these organs occurs through a variety of pathways; subtle physiological changes in one of them are compensated by the other. Histopathological cardiac evaluation through routine staining presents a limitation to identify specific or discreet lesions in the cardiomyocytes. This study aimed to evaluate serum troponin levels in cats with CKD, associated with clinical and pathological findings, as well as to correlate the morphostructural cardiac lesions to determine their distribution through macroscopic and histological assessments and anti-cardiac troponin C (cTnC) immunohistochemistry (IHC). To this end, 20 cats (18 diagnosed with CKD and two controls) were selected. Anti-human cTnC IHC was conducted after necropsy and separation in eight regions of each collected heart. Heart fragments from two cats without CKD were used as controls. The anti-human cTnC antibody is useful in detecting cardiac lesions and has shown decreased expression in cardiomyocytes of cats with CKD. Serum troponin was above the reference values in 11/18 (61.11%) animals and decreased expression for the cTnC antibody was observed in individual cardiomyocytes in 9/18 (50%) animals. It was verified that the number of regions with decreased expression for the cTnC antibody in cardiomyocytes is significantly correlated with serum troponin. The anti-human cTnC antibody has been found effective in detecting cardiac lesions and has shown decreased expression in the cardiomyocytes of cats with CKD. Correlation was observed between increased serum cTnI and loss of immunoreactivity at anti-cTnC antibody IHC in cats with CKD, which proves damage to cardiomyocytes secondary to kidney disease.(AU)

A doença renal crônica (DRC) é caracterizada por lesões morfoestruturais irreversíveis, que podem evoluir progressivamente para insuficiência renal crônica e falência renal. Sabe-se que o coração e os rins mantêm estreita relação e a comunicação entre esses órgãos ocorre por uma variedade de vias; alterações fisiológicas sutis em um desses órgãos são compensadas pelo outro. A avaliação histopatológica cardíaca mediante a colorações rotineiras são limitadas para identificar lesões específicas ou discretas em cardiomiócitos. O presente trabalho teve como objetivos avaliar os níveis séricos de troponina em gatos com DRC, associados aos achados clínico-patológicos, bem como correlacionar as lesões cardíacas morfoestruturais, a fim de determinar a distribuição destas, por meio da avaliação macroscópica, histológica e imuno-histoquímica com anti-cTnC. Neste estudo foram selecionados 20 gatos (18 diagnosticados com DRC e 2 animais controle). Para a aplicação da técnica de imuno-histoquímica anti-troponina C humana, necropsias foram realizadas e cada coração coletado separadamente em 8 regiões. Fragmentos do coração de 2 gatos sem lesão cardíaca foram utilizados como controle. O anticorpo anti-TnC humano é útil na detecção de lesões cardíacas e apresentou expressão diminuída em cardiomiócitos de gatos com DRC. Em 11/18 animais (61,11%) a troponina sérica encontrava-se acima dos valores de referência e foram observadas diminuição da expressão para anticorpo-cTnC em cardiomiócitos individuais em 9/18 (50%). Notou-se que o número de regiões com diminuição da expressão para anticorpo-cTnC em cardiomiócitos está significativamente correlacionado com a troponina sérica. O anticorpo anti-TnC humano se mostrou eficaz para detectar lesões cardíacas e demonstrou diminuição da expressão nos cardiomiócitos de gatos com DRC. Houve correlação entre o aumento da CTnI sérica e perda da imunorretividade na avaliação imuno-histoquímica com anticorpo anti-TnC em gatos com DRC o que comprova danos em cardiomiócitos secundários a doença renal.(AU)

Animals , Cats , Immunohistochemistry , Cats/injuries , Heart , Kidney , Kidney Diseases/diagnosis , Kidney Diseases/pathology , Troponin
Int. braz. j. urol ; 46(1): 15-25, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1056363


ABSTRACT 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.

Humans , Sarcoidosis/pathology , Kidney Diseases/pathology , Sarcoidosis/diagnosis , Sarcoidosis/therapy , Biopsy , Chronic Disease , Hypercalciuria/diagnosis , Hypercalciuria/pathology , Hypercalcemia/diagnosis , Hypercalcemia/pathology , Kidney Diseases/diagnosis , Kidney Diseases/therapy
Braz. arch. biol. technol ; 63: e20200131, 2020. tab, graf
Article in English | LILACS | ID: biblio-1132247


Abstract Gallic acid (GA), as a strong antioxidant, was selected in this study to investigate its possible nephroprotective effects against gentamicin (GM)-induced nephrotoxicity. Twenty-four rats were separated into three groups (n=8): group 1 (control group) received saline (0.5 mL/day), group 2 (GM group) received GM (100 mg/kg/day), and group 3 (treated group) received GM (100 mg/kg/day) and GA (100mg/kg/day). All treatments were performed intraperitoneally for 12 days. After 12 days, the rats were euthanized, and kidneys were removed immediately. For serum preparation, blood samples were collected before killing. Kidney paraffin sections were prepared from one of the kidneys and stained by the periodic acid-Schiff process. GA significantly decreased GM-induced renal histopathological injuries, including tubular necrosis, tubular cast, and leucocyte infiltration compared with the GM group. Additionally, GA significantly improved proteinuria, serum levels of urea and creatinine, and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) compared with nephrotoxic animals. Furthermore, GA caused a significant improvement in the levels of cholesterol (Chol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and cardiac risk ratios 1 and 2 in comparison with nephrotoxic animals. GA administration was observed to significantly improve the levels of lipid peroxidation, nitric oxide (NO), and glutathione (GSH) compared with the GM group. Finally, the activities and gene expression levels of catalase (CAT) and glutathione peroxidase (GPX) significantly increased following GA administration compared with the GM group. Our results indicated that GA has potential protective effects against GM nephrotoxicity by reducing oxidative stress in rats.

Animals , Male , Rats , Gentamicins/adverse effects , Oxidative Stress/drug effects , Gallic Acid/therapeutic use , Kidney Diseases/drug therapy , Anti-Bacterial Agents/adverse effects , Antioxidants/therapeutic use , Biomarkers , Cholesterol , Rats, Wistar , Disease Models, Animal , Gallic Acid/chemistry , Kidney Diseases/chemically induced , Kidney Diseases/pathology , Lipoproteins, HDL , Lipoproteins, LDL
Braz. j. med. biol. res ; 53(6): e8625, 2020. tab, graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS | ID: biblio-1132515


Amyloidosis comprises a group of disorders that accumulate modified autologous proteins in organs, mainly the kidneys. Few studies have addressed the amyloid compartmental distribution and associated clinical outcomes. The aim of this study was to present a case series of renal amyloidosis correlating histopathological data with glomerular filtration rate (GFR) during kidney biopsy. We studied 53 cases reviewed by nephropathologists from 2000 to 2018 in a single kidney biopsy center in Brazil. GFR was estimated using the CKD-EPI formula. Cases were divided into Group A ≥60 and Group B <60 mL·min−1·(1.73 m2)−1 using the estimated GFR during kidney biopsy. Semiquantitative histopathological study was performed, including extension and distribution of amyloid deposits by compartments (glomeruli, tubulointerstitial tissue, and vessels). Statistical analyses were made to understand associations with lower GFR. No difference was seen for age, gender, proteinuria, hematuria, subtype of amyloid protein, arteriosclerosis, interstitial fibrosis/infiltrate, or glomerular and interstitial amyloid deposits. After a previous P value <0.1 in the descriptive analysis, the following variables were selected: globally sclerotic glomeruli, high blood pressure, and the extension of vascular amyloid deposition. A binary logistic regression model with GFR as the dependent variable showed history of hypertension and vascular amyloid to be robust and independent predictors of Group B <60 mL·min−1·(1.73 m2)−1. Beyond the histopathologic diagnosis of amyloidosis, a semiquantitative approach on renal biopsy could provide new insights. Vascular amyloid is an independent predictor of renal dysfunction in cases of renal amyloidosis.

Humans , Male , Female , Adult , Middle Aged , Aged , Glomerular Filtration Rate , Amyloid/physiology , Amyloidosis/pathology , Kidney/pathology , Kidney Diseases/pathology , Biopsy , Retrospective Studies , Amyloidosis/physiopathology , Kidney/physiopathology , Kidney Diseases/physiopathology
J. bras. nefrol ; 41(3): 393-399, July-Sept. 2019. graf
Article in English | LILACS | ID: biblio-1040251


Abstract Lipoprotein glomerulopathy (LPG) is an uncommon cause of nephrotic syndrome and/or kidney failure. At microscopy, LPG is characterized by the presence of lipoprotein thrombi in dilated glomerular capillaries due to different ApoE mutations. ApoE gene is located on chromosome 19q13.2, and can be identified in almost all serum lipoproteins. ApoE works as a protective factor in atherosclerosis due its interaction with receptor-mediated lipoprotein clearance and cholesterol receptor. Most common polymorphisms include ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3, and ApoE4/4. All age-groups can be affected by LPG, with a discrete male predominance. Compromised patients typically reveal dyslipidemia, type III hyperlipoproteinemia, and proteinuria. LPG treatment includes fenofibrate, antilipidemic drugs, steroids, LDL aphaeresis, plasma exchange, antiplatelet drugs, anticoagulants, urokinase, and renal transplantation. Recurrence in kidney graft suggests a pathogenic component(s) of extraglomerular humoral complex resulting from abnormal lipoprotein metabolism and presumably associated to ApoE.

Resumo A glomerulopatia por lipoproteínas (GLP) é uma patologia rara que causa síndrome nefrótica e/ou insuficiência renal. Na microscopia, a GLP é caracterizada pela presença de trombos de lipoproteínas em capilares glomerulares dilatados devido a diferentes mutações no gene da ApoE. O gene da ApoE está localizado no cromossomo 19q13.2 e pode ser identificado em quase todas as lipoproteínas séricas. A ApoE age como fator de proteção na arterioesclerose por conta de sua interação com a depuração de lipoproteínas mediada por receptores e com o receptor de colesterol. Dentre os polimorfismos mais comuns destacam-se ApoE2/2, ApoE3/2, ApoE3/3, ApoE4/2, ApoE4/3 e ApoE4/4. A GLP pode acometer indivíduos de todas as faixas etárias, com discreta predominância do sexo masculino. Pacientes afetados tipicamente apresentam dislipidemia, hiperlipoproteinemia tipo III e proteinúria. O tratamento da GLP é conduzido com fenofibrato, antilipêmicos, corticosteroides, LDL-aferese, troca de plasma, antiplaquetários, anticoagulantes, uroquinase e transplante renal. Recidiva no enxerto renal indica a existência de componentes patogênicos do complexo humoral extraglomerular resultante de metabolismo lipoproteico anômalo, possivelmente associado a ApoE.

Humans , Male , Female , Child, Preschool , Adult , Middle Aged , Kidney Diseases/pathology , Kidney Diseases/therapy , Apolipoproteins E/genetics , Sex Factors , Kidney Transplantation , Treatment Outcome , Kidney Diseases/complications , Kidney Diseases/genetics , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/etiology , Mutation , Hypolipidemic Agents/therapeutic use
Int. j. morphol ; 37(2): 438-447, June 2019. tab, graf
Article in English | LILACS | ID: biblio-1002240


Obesity is a modifiable risk factor for the development and progression of kidney disease. Obesity may harm kidneys in individuals without hypertension, diabetes, or pre-existing renal disease. Ginger, Zingiber officinale, has many beneficial pharmaceutical benefits. This study aimed to evaluate the Zingiber officinale protective effect against obesity complications which induced by high fat diet and caused renal dysfunctions. The study period was two months, and the experimental animals' groups were four, 80 Wistar rats were appropriated similarly 20 animals/group: control group; ginger extract group (GE); high-fat diet (HFD); and GE+HFD group. Body and fat weight, creatinine, leptin, TNF-α, total antioxidants, renal histopathological and ultrastructure were investigated. Rats in group of HFD showed a significant increase (P<0.05) in the body and fat weights, creatinine, leptin and TNF-α, and significant decrease (P<0.05) in total antioxidants (TAS). Ginger administration significantly showed the protective restoring the altered parameters. Furthermore, rats co-treated with ginger extract improved the histopathological and ultrastructural renal injury induced by obesity. The study concluded that the ginger extract used could suppress and decrease the renal damage induced by high-fat diet as it possesses potential medicinal values.

La obesidad es un factor de riesgo modificable para el desarrollo y la progresión de la enfermedad renal. La obesidad puede dañar los riñones en personas sin hipertensión, diabetes o enfermedad renal preexistente. El jengibre, Zingiber officinale, tiene muchos beneficios farmacéuticos. Este estudio tuvo como objetivo evaluar el efecto protector de Zingiber officinale en las complicaciones de la obesidad inducida por una dieta alta en grasas y las enfermedad renal. El período de estudio fue de dos meses, y los grupos de animales experimentales fueron cuatro, se asignaron 80 ratas Wistar de manera similar, 20 animales por grupo: grupo de control; grupo de extracto de jengibre (GE); dieta alta en grasas (DAG); y el grupo GE + DAG. Se evaluó el peso corporal y la grasa, creatinina, leptina, TNF-α, antioxidantes totales, histopatología renal y ultraestructura. Las ratas en el grupo de DAG mostraron un aumento significativo (P<0,05) en el peso corporal y de grasa, creatinina, leptina y TNF-a, y una disminución significativa (P<0,05) en los antioxidantes totales. La administración de jengibre mostró una protección significativa restaurando los parámetros alterados. Además, las ratas tratadas conjuntamente con extracto de jengibre mejoraron la lesión renal histopatológica y ultraestructural inducida por la obesidad. El estudio concluyó que el extracto de jengibre podría suprimir y disminuir el daño renal inducido por la dieta alta en grasas, ya que posee potenciales valores medicinales.

Animals , Rats , Plant Extracts/pharmacology , Ginger/chemistry , Diet, High-Fat/adverse effects , Kidney Diseases/drug therapy , Obesity/complications , Body Weight , Tumor Necrosis Factor-alpha/analysis , Rats, Sprague-Dawley , Creatinine/analysis , Leptin/analysis , Microscopy, Electron, Transmission , Kidney/pathology , Kidney Diseases/pathology
Rev. Assoc. Med. Bras. (1992) ; 65(3): 441-445, Mar. 2019. tab
Article in English | LILACS | ID: biblio-1003045


SUMMARY INTRODUCTION: We analyzed the distribution and frequency of glomerular diseases in patients biopsied between 1992 and 2016 in centers that make up the AMICEN (Minas Gerais Association of Nephrology Centers). METHODS: We analyzed the biopsy reports of patients from 9 AMICEN nephrology centers. We took note of their age, gender, ultrasound use, post-biopsy resting time, whether the kidney was native or a graft, number of glomeruli and indication for the biopsy. The kidney biopsy findings were broken down into four categories: glomerular and non-glomerular diseases, normal kidneys and insufficient material for analysis. Those patients diagnosed with glomerular diseases were further divided into having primary or secondary glomerular diseases. RESULTS: We obtained 582 biopsy reports. The median age was 38 years (1 to 85). The number of glomeruli varied between 0 and 70 (median = 13.0). In total, 97.8% of the biopsies were ultrasound guided. The main indication was nephrotic syndrome (36.9%), followed by hematuria-proteinuria association (16.2%). Primary glomerular diseases proved to be the most frequent (75.3%), followed by secondary diseases (24.7%). Among the primary glomerular diseases, FSGS was found at a higher frequency (28.8%), while among the secondary diseases, SLE was the most prevalent (42.4%). Regarding prevalence findings, those for both primary and secondary diseases were similar to those found in the large Brazilian registries published thus far. CONCLUSION: Glomerular disease registries are an important tool to identify the prevalence of such disease in regions of interest and can serve as an instrument to guide public policy decisions concerning the prevention of terminal kidney diseases.

RESUMO INTRODUÇÃO: Analisamos a distribuição e frequência de doenças glomerulares de pacientes biopsiados entre 1992 e 2016 em centros que compõem a Amicen (Associação de Minas Gerais de Nefrologia). MÉTODOS: Analisamos os relatórios de biópsia de pacientes de nove centros de nefrologia da Amicen. Observamos idade, gênero, uso de ultrassom, tempo de descanso pós-biópsia, se o rim era nativo ou um enxerto, número de glomérulos e indicação para a biópsia. Os achados da biópsia do rim foram divididos em quatro categorias: doenças glomerulares e não glomerulares, rins normais e material insuficiente para análise. Os pacientes diagnosticados com doenças glomerulares foram ainda divididos em doenças glomerulares primárias ou secundárias. RESULTADOS: Obtivemos 582 relatórios de biópsia. A idade mediana foi de 38 anos (1 a 85). O número de glomérulos variou entre zero e 70 (mediana = 13,0). No total, 97,8% das biópsias foram guiadas por ultrassom. A principal indicação foi síndrome nefrótica (36,9%), seguida de associação hematúria-proteinúria (16,2%). As doenças glomerulares primárias revelaram-se as mais frequentes (75,3%), seguidas de doenças secundárias (24,7%). Entre as doenças glomerulares primárias, o FSGS foi encontrado em maior frequência (28,8%), enquanto nas doenças secundárias, o lúpus eritematoso sistêmico foi o mais prevalente (42,4%). Quanto aos achados de prevalência, aqueles para doenças primárias e secundárias foram semelhantes aos encontrados nos grandes registros brasileiros publicados até o momento. CONCLUSÃO: Os registros de doenças glomerulares são uma ferramenta importante para identificar a prevalência dessas doenças em regiões de interesse e pode servir como um instrumento para orientar decisões de políticas públicas relativas à prevenção de doenças renais terminais.

Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Aged , Aged, 80 and over , Young Adult , Glomerulonephritis/epidemiology , Kidney Diseases/epidemiology , Biopsy , Brazil/epidemiology , Registries/statistics & numerical data , Prevalence , Cross-Sectional Studies , Glomerulonephritis/pathology , Kidney/pathology , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Middle Aged , Nephrology/statistics & numerical data
Rev. méd. Chile ; 147(3): 390-394, mar. 2019. graf
Article in Spanish | LILACS | ID: biblio-1004362


Goodpasture Syndrome is described as a single episode disease entity. It is diagnosed with the demonstration of antiglomerular basement (anti-GBM) antibodies in plasma or renal tissue. Although the recurrence of anti-GBM disease is rare, it has been reported in up to 3% of cases. Recurrence with negative anti-GBM antibodies in plasma is even less frequent We report a 63 years old male in whom anti-GBM disease recurred without detectable anti-GBM antibodies in plasma, despite having positive antibodies at the onset.

Humans , Male , Middle Aged , Autoantibodies/analysis , Anti-Glomerular Basement Membrane Disease/pathology , Recurrence , Biopsy , Prednisone/therapeutic use , Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use , Fluorescent Antibody Technique , Anti-Glomerular Basement Membrane Disease/drug therapy , Anti-Glomerular Basement Membrane Disease/diagnostic imaging , Cyclophosphamide/therapeutic use , Kidney Diseases/pathology , Kidney Glomerulus/pathology , Anti-Bacterial Agents/therapeutic use
Rev. Assoc. Med. Bras. (1992) ; 65(2): 100-104, Feb. 2019.
Article in English | LILACS | ID: biblio-990322


The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Humans , Male , Female , Biopsy/methods , Laparoscopy/methods , Kidney/pathology , Kidney Diseases/pathology , Retroperitoneal Space , Tomography, Emission-Computed , Practice Guidelines as Topic , Kidney Diseases/diagnostic imaging
Acta cir. bras ; 34(12): e201901201, 2019. graf
Article in English | LILACS | ID: biblio-1054690


Abstract 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.

Animals , Male , Organometallic Compounds/pharmacology , Ruthenium/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Nitric Oxide Donors/pharmacology , Meloxicam/adverse effects , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Random Allocation , Reproducibility of Results , Rats, Wistar , Fractals , Kidney Diseases/pathology
Braz. j. med. biol. res ; 52(11): e8772, 2019. graf
Article in English | LILACS | ID: biblio-1039259


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.

Animals , Male , Pyridones/pharmacology , Ureteral Obstruction/pathology , Apoptosis/drug effects , Epithelial Cells/drug effects , Kidney Diseases/pathology , Pyridones/metabolism , Blood Urea Nitrogen , Fibrosis , Angiotensin-Converting Enzyme Inhibitors/metabolism , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Enalapril/metabolism , Enalapril/pharmacology , Random Allocation , Rats, Sprague-Dawley , Creatinine/blood , Collagen Type I/drug effects , Collagen Type I/metabolism , Disease Models, Animal , Transcription Factor CHOP/drug effects , Apoptotic Protease-Activating Factor 1/drug effects , Apoptotic Protease-Activating Factor 1/metabolism , Fas-Associated Death Domain Protein/drug effects , Fas-Associated Death Domain Protein/metabolism
Int. braz. j. urol ; 44(6): 1243-1251, Nov.-Dec. 2018. tab, graf
Article in English | LILACS | ID: biblio-975668


ABSTRACT Introduction: We investigated whether Oltipraz (OPZ) attenuated renal fibrosis in a unilateral ureteral obstruction (UUO) rat model. Materials and Methods: We randomly divided 32 rats into four groups, each consisting of eight animals as follows: Rats in group 1 underwent a sham operation and received no treatment. Rats in group 2 underwent a sham operation and received OPZ. Rats in group 3 underwent unilateral ureteral ligation and received no treatment. Group 4 rats were subjected to unilateral ureteral ligation plus OPZ administration. Transforming growth factor beta-1 (TGF-β1), E-cadherin, nitric oxide (NO) and hydroxyproline levels were measured. Histopathological and immunohistochemical examinations were carried out. Results: TGF-β1, NO and E-cadherin levels in the UUO group were significantly higher than the sham group and these values were significantly different in treated groups compared to the UUO group. In rats treated with UUO + OPZ, despite the presence of mild tubular degeneration and less severe tubular necrosis, glomeruli maintained a better morphology when compared to the UUO group. Expressions of α-SMA in immunohistochemistry showed that the staining positivity decreased in the tubules of the OPZ-treated group. Conclusions: While the precise mechanism of action remains unknown, our results demonstrated that OPZ exerted a protective role in the UUO-mediated renal fibrosis rat model highlighting a promising therapeutic potency of Nrf2-activators for alleviating the detrimental effects of unilateral obstruction in kidneys.

Animals , Male , Rats , Pyrazines/therapeutic use , Ureteral Obstruction/complications , NF-E2-Related Factor 2/therapeutic use , Kidney Diseases/drug therapy , Thiones , Thiophenes , Ureteral Obstruction/pathology , Ureteral Obstruction/drug therapy , Fibrosis/etiology , Fibrosis/drug therapy , Immunohistochemistry , Cadherins/blood , Rats, Wistar , Disease Models, Animal , Transforming Growth Factor beta1/blood , Hydroxyproline/blood , Kidney Diseases/etiology , Kidney Diseases/pathology , Nitric Oxide/blood
J. bras. nefrol ; 40(3): 291-295, July-Sept. 2018. tab, graf
Article in English | LILACS | ID: biblio-975909


ABSTRACT Introduction: Sarcoidosis is a systemic inflammatory disease of unknown etiology, characterized by the presence of non-caseating granulomas in several organs; renal impairment alone is a rare condition. When it affects the kidneys, the most prevalent manifestations are hypercalcemia and hypercalciuria. This paper aims to address the topic of renal sarcoidosis, by means of a case report, and reinstate the importance of histopathology in its diagnosis. Methods: The data came from an observational clinical study with a qualitative approach, through an interview with the renal sarcoidosis patient and data from her medical records. Case report: Patient D.M.S., 50 years old, Caucasian, presented with reddish eyes and body pains lasting for fifteen days as first manifestations of the disease. Upon kidney ultrasound scan, we found renal parenchymal nephropathy. Serial renal function and metabolic tests reported anemia and progressive urea and creatinine changes, as well as hypercalcemia and hypercalciuria, confirming acute kidney failure (AKF). A histopathological examination suggested the diagnosis, which was confirmed by clinical, laboratory and histopathological data. There was therapeutic resolution after steroid therapy. Discussion: The symptomatology of sarcoidosis is diverse and often non-specific. Renal manifestation, which usually occurs after organ involvement, is present in less than 5% of patients, and about 1% to 2% of these patients may develop AKF. Conclusions: The use of histopathology together with clinical and laboratory data to diagnose isolated renal sarcoidosis, rule out other etiologies and introduce early treatment is of paramount importance.

RESUMO Introdução: A sarcoidose é uma doença inflamatória sistêmica de etiologia desconhecida caracterizada pela presença de granulomas não caseosos em diversos órgãos, sendo raro o comprometimento puramente renal. Quando acomete os rins, as manifestações mais prevalentes são hipercalcemia e hipercalciúria. Este trabalho objetiva abordar o tema sarcoidose renal, por meio de relato de caso, e reafirmar a importância da histopatologia no diagnóstico. Métodos: Os dados foram obtidos por estudo clínico observacional com abordagem qualitativa, por meio de entrevista com a paciente portadora de sarcoidose renal e dados de seu prontuário médico. Relato de caso: Paciente D.M.S., 50 anos, caucasiana, apresentou como primeiras manifestações da doença olhos avermelhados e dores no corpo com duração de quinze dias. Em ultrassonografia renal, foi constatada nefropatia parenquimatosa renal bilateral. Testes seriados de função e metabolismo renal relataram anemia e alteração progressiva de ureia e creatinina, além de hipercalcemia e hipercalciúria, constatando quadro de insuficiência renal aguda (IRA). Foi indicado exame histopatológico que sugeriu o diagnóstico, confirmado pelos dados clínicos, laboratoriais e histopatológico somados. Houve resolução terapêutica após corticoterapia. Discussão: A sintomatologia da sarcoidose é diversificada e, muitas vezes, inespecífica. A manifestação renal, que ocorre geralmente após o acometimento de outros órgãos, está presente em menos de 5% dos pacientes, e cerca de 1% a 2% destes podem desenvolver IRA. Conclusões: É de suma importância o auxílio da histopatologia somada aos dados clínicos e laboratoriais para diagnóstico de sarcoidose renal isolada, exclusão de outras etiologias e introdução de terapêutica precoce.

Humans , Female , Middle Aged , Sarcoidosis/pathology , Kidney Diseases/pathology
Acta cir. bras ; 33(6): 508-517, June 2018. tab, graf
Article in English | LILACS | ID: biblio-949360


Abstract Purpose: To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. Methods: Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. Results: Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. Conclusion: The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.

Animals , Male , Ozone/pharmacology , Acetylcysteine/pharmacology , Contrast Media/adverse effects , Kidney Diseases/chemically induced , Kidney Diseases/prevention & control , Antioxidants/pharmacology , Reference Values , Spectrophotometry/methods , Urea/blood , Ioxaglic Acid/adverse effects , Random Allocation , Reproducibility of Results , Treatment Outcome , Rats, Wistar , Oxidative Stress/drug effects , Creatinine/blood , Protein Carbonylation , Lipocalin-2/blood , Kidney/drug effects , Kidney/pathology , Kidney Diseases/pathology
Int. braz. j. urol ; 44(3): 608-616, May-June 2018. tab, graf
Article in English | LILACS | ID: biblio-954055


ABSTRACT Purpose: To identify the fetal stem cell (FSC) response to maternal renal injury with emphasis on renal integrity improvement and Y chromosome detection in damaged maternal kidney. Materials and Methods: Eight non-green fluorescent protein (GFP) transgenic Sprague-Dawley rats were mated with GFP-positive transgenic male rats. Renal damage was induced on the right kidney at gestational day 11. The same procedure was performed in eight non-pregnant rats as control group. Three months after delivery, right ne- phrectomy was performed in order to evaluate the injured kidney. The fresh perfused kidneys were stained with anti-GFP antibody. Polymerase chain reaction (PCR) assay was also performed for the Y chromosome detection. Cell culture was performed to detect the GFP-positive cells. Technetium-99m-DMSA renal scan and single-photon emission computed tomography (SPECT) were performed after renal damage induction and 3 months later to evaluate the improvement of renal integrity. Results: The presence of FSCs was confirmed by immune histochemical staining as well as immunofluorescent imaging of the damaged part. Gradient PCR of female rat purified DNA demonstrated the presence of Y-chromosome in the damaged maternal kidney. Moreover, the culture of kidney cells showed GPF- positive cells by immuno- fluorescence microscopy. The acute renal scar was repaired and the integrity of dam- aged kidney reached to near normal levels in experimental group as shown in DMSA scan. However, no significant improvement was observed in control group. Conclusion: FSC seems to be the main mechanism in repairing of the maternal renal injury during pregnancy as indicated by Y chromosome and GFP-positive cells in the sub-cultured medium.

Animals , Male , Female , Pregnancy , Wound Healing/physiology , Chimerism , Fetal Stem Cells/physiology , Kidney Diseases/physiopathology , Maternal-Fetal Exchange/physiology , Time Factors , Y Chromosome , Immunohistochemistry , Tomography, Emission-Computed, Single-Photon , Cells, Cultured , Polymerase Chain Reaction , Fluorescent Antibody Technique , Rats, Sprague-Dawley , Radiopharmaceuticals , Technetium Tc 99m Dimercaptosuccinic Acid , Disease Models, Animal , Kidney Diseases/pathology , Kidney Diseases/diagnostic imaging
Int. braz. j. urol ; 44(3): 642-644, May-June 2018. graf
Article in English | LILACS | ID: biblio-954048


ABSTRACT Renal replacement lipomatosis is a condition characterized by varying degrees of renal parenchymal atrophy and perirenal fibrofatty proliferation secondary to chronic inflammation such as xanthogranulomatous pyelonephritis. In severe cases, imaging findings can be misdiagnosed as retroperitoneal liposarcoma.

Humans , Male , Retroperitoneal Neoplasms/diagnostic imaging , Pyelonephritis, Xanthogranulomatous/diagnosis , Kidney Diseases/diagnostic imaging , Lipomatosis/diagnostic imaging , Liposarcoma/diagnostic imaging , Retroperitoneal Neoplasms/pathology , Pyelonephritis, Xanthogranulomatous/pathology , Radiography, Abdominal , Tomography, X-Ray Computed , Diagnosis, Differential , Kidney Diseases/pathology , Lipomatosis/pathology , Liposarcoma/pathology , Middle Aged
J. bras. nefrol ; 39(4): 376-383, Oct.-Dec. 2017. tab, graf
Article in English | LILACS | ID: biblio-893801


Abstract Introduction: A report on the prevalence of glomerular disease diagnosed via renal biopsy in Salvador, BA, Brazil was published in 1973 and showed a predominance of membranoproliferative glomerulonephritis, which was frequently associated with hepatosplenic schistosomiasis. Objective: In this study, we investigate the potential changes in the distribution of glomerular diseases after a period of important epidemiological transition in Brazil. Methods: Pathology reports of all patients subjected to kidney biopsy from 2003 to 2015 in a referral nephrology service were reviewed. Clinical, laboratorial and pathological diagnoses were collected for analysis. Histological slides of the biopsies performed between 2003 and 2006 were reviewed to examine the accuracy of the estimates based on the pathology reports. Results: Among the biopsies performed during the time period, 1,312 met the inclusion criteria for the study. Focal and segmental glomerulosclerosis was the most prevalent diagnosis, followed by lupus nephritis. However, a trend toward a decrease in the prevalence of focal and segmental glomerulosclerosis was detected (p < 0.05), and an increase in lupus (p < 0.0001) and membranous glomerulonephritis (p < 0.005) was observed. Conclusion: The data presented herein suggest the occurrence of changes in the distribution of nephrological diseases in Salvador, Brazil. The disease that was most prevalent shifted from membranoproliferative glomerulonephritis to focal and segmental glomerulosclerosis from 1975 to 2006 and from focal and segmental glomerulosclerosis to lupus nephritis from 2006 to 2015.

Resumo Introdução: um relatório sobre a prevalência de glomerulopatia diagnosticada por biópsia renal em Salvador foi publicado em 1973, demonstrando o predomínio de glomerulonefrite membranoproliferativa, frequentemente associada a esquistossomose hepatoesplênica. Objetivo: no presente estudo, investigamos as possíveis mudanças na distribuição das glomerulopatias após um período de importantes transições epidemiológicas no Brasil. Métodos: foram revisados todos os relatos de pacientes submetidos a biópsia renal de 2003 a 2015 em um serviço de referência em nefrologia. Diagnósticos clínicos, laboratoriais e patológicos foram colhidos para análise. Lâminas histológicas das biópsias executadas entre 2003 e 2006 foram revisadas para avaliar a precisão das estimativas baseadas nos laudos anatomopatológicos. Resultados: entre as biópsias realizadas durante o período em questão, 1.312 satisfizeram os critérios de inclusão do estudo. Glomeruloesclerose segmentar e focal foi o diagnóstico mais prevalente, seguido de nefrite lúpica. Entretanto, foi detectada tendência de queda na prevalência da glomeruloesclerose segmentar e focal (p < 0,05) e de elevação nos casos de lúpus (p < 0,0001) e glomerulonefrite membranosa (p < 0,005). Conclusão: os dados apresentados neste estudo sugerem a ocorrência de mudanças na distribuição das doenças nefrológicas em Salvador. A doença mais prevalente passou de glomerulonefrite membranoproliferativa para glomeruloesclerose segmentar e focal de 1975 a 2006 e de glomeruloesclerose segmentar e focal para nefrite lúpica de 2006 a 2015.

Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Kidney Diseases/pathology , Kidney Diseases/epidemiology , Kidney Glomerulus , Time Factors , Biopsy , Brazil/epidemiology , Prevalence
Int. j. med. surg. sci. (Print) ; 4(4): 1251-1258, dic. 2017. ilus, graf
Article in English | LILACS | ID: biblio-1282099


Although studies suggest adverse effects of pesticides, human exposure to insecticides in homes is increasing and reports on their health effects are limited. The study investigated nephrotoxic effects of organo phosphate and carbamate insecticides, DD-Force and Baygon, in albino rats. Forty-five albino rats divided into groups were exposed to DD-Force (dichlorvos) or Baygon (propoxur) indoor insecticidein wooden boxes in separate exposure duration of 1, 2, 3 and 4 hours/day for 14 consecutive days. Serum and kidney tissue obtained after sacrifice were used to determine markers of renal damage and histopathological analysis, respectively. Exposure of rats to the insecticides showed duration-dependent significant increases (p<0.05) in serum levels of urea, uric acid and creatinine compared to control. However, rats exposed to DD-Force insecticide induced significantly higher levels of urea, uric acid and creatinine compared to Baygon (p<0.05). Histopathological lesions were observed in rats exposed to the insecticides, particularly in the exposure duration of 3 or 4 hours/day. These findings suggest that acute exposure to DD-Force and Baygonis nephrotoxic and may induce renal damage in rats.

Aunque los estudios sugieren efectos adversos de los pesticidas, la exposición humana a los insecticidas en los hogares está aumentando y los informes sobre sus efectos sobre la salud son limitados. Este estudio investigó los efectos nefrotóxicos de los insecticidas órgano fosfato y carbamato, DD-Force y Baygon, en ratas albinas. Cuarenta y cinco ratas albinas divididas en grupos fueron expuestas a DD-Force (diclorvos) o Baygon (propoxur) insecticidas de interior en cajas de madera en una duración de exposición separada de 1, 2, 3 y 4 horas / día durante 14 días consecutivos. Muestras séricas y de tejido renal obtenidas después del sacrificio se utilizaron para determinar los marcadores de daño renal y el análisis histopatológico, respectivamente. La exposición de las ratas a los insecticidas mostró aumentos significativos dependientes de la duración (p<0.05) en los niveles séricos de urea, ácido úrico y creatinina en comparación con el control. Sin embargo, las ratas expuestas al insecticida DD-Force indujeron niveles significativamente más altos de urea, ácido úrico y creatinina en comparación con Baygon (p<0.05). Se observaron lesiones histopatológicas en ratas expuestas a los insecticidas, particularmente en la duración de exposición de 3 o 4 horas/día. Estos hallazgos sugieren que la exposición aguda a DD-Force y Baygonis nephrotóxico y puede inducir daño renal en ratas.

Rats , Propoxur/toxicity , Dichlorvos/toxicity , Insecticides, Organochlorine/adverse effects , Insecticides/toxicity , Kidney Diseases/chemically induced , Urea/blood , Uric Acid/blood , Creatinine/blood , Kidney Diseases/pathology
Acta cir. bras ; 31(11): 759-764, Nov. 2016. tab, graf
Article in English | LILACS | ID: biblio-827667


ABSTRACT PURPOSE: To analyze the influence of chlorpromazine on renal histology of rats submitted to ischemia and reperfusion injury. METHODS: Sixteen Wistar rats - split in two groups - have been used: control group, receiving 3 mg/kg isotonic saline solution through caudal vein, and, the chlorpromazine group, receiving 3 mg/kg-IV of such medication. The nephrectomy of the left kidney lower third was carried out; immediately, the test-drug was administrated. After 15 minutes of test-drug administration, the renal pedicle was clamped; in 60 minutes of ischemia it was released. After 24 hours of the renal reperfusion, the rats were, once more, anesthetized and submitted to total left nephrectomy, and, afterwards, to euthanasia. Histological findings regarding ischemia have been evaluated and compared between the groups. RESULTS: There was no statistical difference related to inferior renal pole histological analysis. Regarding 60-minute renal ischemia, chlorpromazine has statistically reduced the accrual of leucocytes within the vasa recta renis (p=0.036) and the congestion of peritubular capillaries (p=0.041). When conducting joint analysis of histological patterns, the control group showed a median score of 11 and chlorpromazine group of 5.5 (p=0.036). CONCLUSION: Chlorpromazine significantly reduced the occurrence of secondary damage to ischemia and reperfusion process in the overall histological analysis.

Animals , Male , Rats , Reperfusion Injury/pathology , Chlorpromazine/pharmacology , Ischemic Preconditioning/methods , Kidney/blood supply , Kidney Diseases/pathology , Rats, Wistar , Disease Models, Animal , Ischemia/pathology , Kidney/pathology