Inflammation and kidney injury attenuated by prior intake of Brazil nuts in the process of ischemia and reperfusion / Inflamação e lesão renal atenuadas pela ingestão prévia de castanha-do-Brasil no processo de isquemia e reperfusão

ABSTRACT Introduction: Ischemia and reperfusion (IR) is a process inherent to the procedures involved in the transplantation of organs that causes inflammation, cell death and cell injury, and may lead to rejection of the graft. It is possible that the anti-inflammatory properties of the Brazil nuts (BN) can mitigate the renal injury caused by IR. Objective: To investigate whether the previous intake of BN reduces the expression of markers of inflammation, injury, and cell death after renal IR. Methods: Male Wistar rats were distributed into six groups (N = 6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN, IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right nephrectomy and occlusion of the left renal artery with a non-traumatic vascular clamp for 30 min. BN was given daily from day 1 to 7 before surgery (SHAM or IR), and maintained until sacrifice (48 h after surgery). Inflammation was evaluated by renal expression of COX-2 and TGF-β, injury by the expression of vimentin, and cell death by apoptosis through caspase-3 expression (immunohistochemistry). Results: Pretreatment with 75 mg of BN reduced renal expression of the COX-2, TGF-β, vimentin, and caspase-3. The dose of 150 mg caused increased expression of COX-2. Conclusion: In experimental IR, the damage can be minimized with a prior low-dose intake of BN, improving inflammation, injury, and cell death.

RESUMO Introdução: Isquemia e reperfusão (IR) é um processo inerente aos procedimentos envolvidos no transplante de órgãos, que causa inflamação, morte celular e lesão, podendo levar à rejeição do enxerto. É possível que a castanha-do-brasil (CB), por suas propriedades anti-inflamatórias, possa atenuar a lesão renal causada pela IR. Objetivo: Investigar se a ingestão prévia de CB reduz a expressão de marcadores renais de inflamação, lesão e morte celular após a IR. Métodos: Ratos Wistar machos foram distribuídos em seis grupos (N = 6/grupo): SHAM (controle), SHAM tratado com 75 ou 150 mg de CB, IR, e IR tratado com 75 ou 150 mg de CB. O procedimento de IR consistiu na nefrectomia à direita e oclusão da artéria renal esquerda por 30 minutos. A castanha foi administrada diariamente por sete dias antes da cirurgia (SHAM ou IR), e mantida até o sacrifício (48 horas pós-cirurgia). A inflamação foi avaliada pela expressão renal de COX-2 e TGF-β; a lesão pela expressão de vimentina, e a morte celular por apoptose pela expressão de caspase-3, por imuno-histoquímica. Resultados: O pré-tratamento com 75 mg de CB reduziu a expressão renal de COX-2, de TGF-β, de vimentina e de caspase-3. A dose de 150 mg causou elevação da expressão de COX-2. Conclusão: No modelo experimental de IR renal, os danos podem ser minimizados com a ingestão prévia de baixas doses de CB, melhorando a inflamação, a lesão e a morte celular.

Captopril alleviates hypertension-induced renal damage, inflammation, and NF-κB activation

Hypertensive renal damage generally occurs during the middle and late stages of hypertension, which is typically characterized by proteinuria and renal inflammation. Captopril, an angiotensin-converting enzyme (ACE) inhibitor, has been widely used for therapy of arterial hypertension and cardiovascular diseases. However, the protective effects of captopril on hypertension-induced organ damage remain elusive. The present study was designed to explore the renoprotective action of captopril in spontaneously hypertensive rats (SHR). The 6-week-old male SHR and age-matched Wistar-Kyoto rats were randomized into long-term captopril-treated (34 mg/kg) and vehicle-treated groups. The results showed that in SHR there was obvious renal injury characterized by the increased levels of urine albumin, total protein, serum creatinine, blood urea nitrogen, renal inflammation manifested by the increased mRNA and protein expression of inflammatory factors including tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase, and enhanced nuclear factor-κB (NF-κB) activation. Captopril treatment could lower blood pressure, improve renal injury, and suppress renal inflammation and NF-κB activation in SHR rats. In conclusion, captopril ameliorates renal injury and inflammation in SHR possibly via inactivation of NF-κB signaling.

Collared Pecary (tayassu tajacu) as a new model of renal ischemic injury induced by clamping the renal artery

PURPOSE: The use of the collared peccary as an experimental model for ischemic nephropathy. METHODS: A total of 12 collared peccary (Tayassu tajacu) was used and ischemic nephropathy was induced in six of these animals that constituted the experimental group (G1) while the other six formed the control group (G2). Ischemic nephropathy was induced surgically by partial occlusion of the left renal artery. The disease course was assessed by hematological tests, serum chemistry, urinalysis, ultrasound (US) and doppler ultrasound function of the renal artery before induction, and at five, 10, 15 and 20 days after surgery. Twenty days after the occlusion, unilateral nephrectomy and histopathological examination were performed to assess renal morphology. RESULTS: Statistical analysis by Fischer's test showed a significant difference (p<0.05) between the control group and the experimental group. The histopathological examination showed glomerular, tubular and interstitial lesions. In the experimental group, 83.3% (5 /6) showed moderate renal lesions and only 16.7% (1/6) were classified with no lesions. The ultrasound examination of the right kidney presented statistical difference between day 5 and day 10 post occlusion. CONCLUSION: The collared peccary as a good experimental model for ischemic renal disease, because it could be manipulated during the research time without death, with health conditions that permit any subsequent procedure for disease therapy. .

Papel de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal / Mitochondria and oxidative stress participation in renal inflammatory process

La muerte celular programada y la fibrosis renal son procesos inherentes a la enfermedad renal crónica y, en tal sentido, ha sido recientemente descripta una clara desregulación de la maquinaria respiratoria mitocondrial en pacientes con enfermedad renal crónica asociada con un aumento del estrés oxidativo. Las células tubulares lesionadas vinculadas a los macrófagos intersticiales y miofibroblastos producen citoquinas y factores de crecimiento que promueven un estado inflamatorio, inducen la apoptosis de las células tubulares y facilitan la acumulación de matriz extracelular. La angiotensina II desempeña un papel central en la fibrogénesis renal y conduce a una rápida progresión de la enfermedad renal crónica. Los niveles crecientes de la angiotensina II inducen citoquinas pro-inflamatorias, la activación de NF-kB, moléculas de adhesión, quimiocinas, factores de crecimiento y estrés oxidativo. Toda la evidencia actual sugiere que la angiotensina II aumenta el estrés oxidativo mitocondrial, regula la inducción de apoptosis y condiciona al estado inflamatorio. Por lo tanto, existiría un papel determinante de las mitocondrias y el estrés oxidativo en el proceso inflamatorio renal. Finalmente, esta revisión resume nuestro actual conocimiento acerca de los posibles mecanismos que contribuirían con la apoptosis modulada por la inflamación y/o el estrés oxidativo durante la enfermedad renal crónica. Además, se propone un nuevo concepto de herramientas anti-inflamatorias que regulan el estrés oxidativo mitocondrial lo cual afectaría directamente al proceso inflamatorio y la apoptosis. Esta idea podría tener consecuencias atractivas sobre el tratamiento de patologías inflamatorias renales y de otras afines.

The apoptosis and renal fibrosis are processes inherent to the chronic kidney disease, and consequently a clear deregulation of the mitochondrial respiratory mechanism has been described in patients with chronic renal disease associated to an increase of the oxidative stress. The injured tubular cells linked to the interstitial macrophages and myofibroblasts produce cytokines and growth factors that encourage an inflammatory condition, inducing the apoptosis of the tubular cells and enabling the accumulation of the extracellular matrix. The angiotensin II has a central role in the renal fibrogenesis leading to a rapid progression of the chronic kidney disease. The growing levels of the angiotensin II induce pro-inflammatory cytokines, the activation of NF-kB, adhesion molecules,chemokines, growth factors, and oxidative stress. The current evidence suggests that the angiotensin II increases the mitochondrial oxidative stress, regulates the induction of the apoptosis and conditions the inflammatory process. Therefore the mitochondria and the oxidative stress would play a determinant role in the renal inflammatory process. Finally, this review summarizes our present knowledge regarding the possible mechanisms that would contribute to the apoptosis conditioned by inflammation and/or oxidative stress during the chronic renal disease. Additionally, a new concept of the anti-inflammatory tools is proposed to regulate the mitochondrial oxidative stress that would directly affect the inflammatory process and apoptosis. This concept could have positive consequences on the treatment of renal inflammatory pathologies and related diseases.

Effect of sirolimus on renal injury induced by bile duct ligation in rats / Efeito do sirolimo na lesão renal induzida pela ligadura do ducto biliar em ratos

PURPOSE: To evaluate the effects of sirolimus (SRL) on renal injury in rats with bile duct ligation. METHODS: A total of 21 male Sprague-Dawley rats weighing 220-260g were used. Group 1 (Sham-control, n=7) rats were undergone laparotomy alone and bile duct was just dissected from the surrounding tissue. Group 2 rats (BDL/Untreated, n=7) were subjected to bile duct ligation and no drug was applied. Group 3 rats (BDL/SRL, n =7) received a daily dose of sirolimus (0.5 mg·day-1xkg-1 dissolved 1 ml in saline) by orogastric tube for 14 days after BDL. At the end of the two-week period, biochemical and histological evaluation were processed. RESULTS: AST, ALT, AP and TB levels values were decreased in group 3 when compared to group 2. There was no significant difference in serum levels of BUN and creatinine among all the experimental groups. Histological evaluation of the liver of BDL/Untreated group rats demonstrated marked portal fibrosis and signs of major bile duct obstruction with prominent portal and lobular inflammation. In BDL/SRL group, moderate damage was seen. Tubular injury scores were higher in the BDL subgroups; however, group 3 rats showed considerably fewer lesions in the tubules and interstitium compared to the group 2 rats. In group 2 animals, in the epithelial cells of proximal tubules presented vacuoles and hydropic changes, atrophy and inflammatory cell infiltrate in the medullar interstitium. CONCLUSIONS: Sirolimus decreased tubulointerstitial lesions in kidney induced by bile duct ligation in rats. The improve effects of sirolimus on renal morphology can be due to improved liver function or due to direct action on the kidney.

OBJETIVO: Investigar os efeitos do sirolimo (SRL) na lesão renal induzida pela ligadura do ducto biliar em ratos. MÉTODOS: Foram utilizados 21 ratos Sprague-Dawley pesando entre 220-260 g. Grupo 1 (Sham-controle, n=7) submetidos a laparotomia e o ducto biliar dissecado do tecido circundante. Grupo 2 (BDL/Não tratado, n=7) foram submetidos a ligadura do ducto biliar e nenhuma droga foi aplicada. Grupo 3 (BDL/SRL, n=7) receberam dose diária de sirolimo (0,5 mg dia-1xkg-1 dissolvido em 1 ml em solução salina) por tubo orogástrico por 14 dias após BDL. Após duas semanas era realizada avaliação bioquímica e histológica. RESULTADOS: Níveis de AST, ALT, AP e TB estavam diminuídos no grupo 3 comparado ao grupo 2. Não houve diferença significante nos níveis séricos de BUN e creatinina em todos os grupos. Observou-se na avaliação histológica evidente fibrose portal e sinais de obstrução do ducto biliar com evidente inflamação portal e lobular. No grupo BDL/SRL verificou-se dano moderado. Lesão tubular foi maior nos subgrupos BDL; entretanto, o grupo 3 mostrou considerável menos lesões nos túbulos e interstício comparados ao grupo 2. No grupo 2 as células epiteliais dos túbulos proximais apresentaram vacúolos e alterações hidrópicas, atrofia e infiltrado celular inflamatório no interstício medular. CONCLUSÕES: Sirolimo diminuiu lesões tubulointersticial no rim induzida pela ligadura do ducto biliar em ratos. Os efeitos benéficos do sirolimo na morfologia renal pode ser devida à melhora da função hepática ou devido à ação direta no rim.

Radiation nephritis: anti-inflammatory effect of dexamethasone in adult Wistar rats (Rattus norvegicus) / Nefritis por radiación: efecto anti-inflamatorio de la dexametasona en ratas Wistar adultas (Rattus norvegicus)

The anti-inflammatory effect of dexamethasone on the irradiated kidneys of adult Wistar rats (Rattus norvegicus) was studied. Eighteen adult Wistar rats were, after acclimatization, randomly divided into 3 groups of 6 animals per group. The control group had normal saline, receiving neither drugs nor radiation. The second group received normal saline and radiation. The third group received pretreatment with dexamethasone at 1mg/kg body weight/day for 2 days followed by radiation. Radiation was delivered to the animals as a single fraction of 2.5 Gy of gamma rays from Cobalt-60 source, using an AECL Theatron 780-C Teletherapy machine. After exposure to the different interventions, the animals were sacrificed on the 14th post-irradiation day and the kidneys dissected out from each animal. The renal tissues were subjected to histological processing, and then studied using an eyepiece objective ruler calibrated with a 2mm stage micrometer for histomorphometric studies. The result of the study showed that all irradiated animals suffered weight loss by the 14th day post-irradiation (p<0.05) irrespective of the additional treatment with dexamethasone and this was statistically significant. Histomorphometry showed that the maximum width of the glomerular capsule was significantly greater in the radiation groups than in the control at p<0.05. The maximal glomerular diameter was significantly greater in irradiated animals compared with the control animals at p<0.05. The outcome of this study showed that the intraperitoneal administration of dexamethasone at 1mg/kg body weight/day for 2 days prior to treatment with irradiation did not prevent weight loss nor ameliorate the swelling of the nephrons resulting from the effect of radiation injury to the Wistar rat.

Fue estudiado el efecto anti-inflamatorio de la dexametasona en riñones irradiados de 18 ratas Wistar adultas (Rattus norvegicus). Luego de la aclimatización, aleatoriamente se dividieron en 3 grupos de 6 animales por grupo. El grupo control recibió una solución salina normal, sin recibir drogas ni radiación. El segundo grupo recibió solución salina normal y radiación. El tercer grupo recibió tratamiento previo con dexametasona con 1 mg / kg de peso corporal / día, durante 2 días, seguido de radiación. Los animales fueron expuestos a radiación con una fracción independiente de 2.5 Gy de rayos gamma por una fuente de Cobalto-60, usando una máquina de teleterapia AECL Theatron 780-C. Después de la exposición a las diferentes intervenciones, los animales fueron sacrificados el día 14 post-irradiación y los riñones de cada uno de los animales fueron disecados. Los tejidos renales fueron sometidos a procesamiento histológico, y luego se estudiaron utilizando un objetivo ocular milimetrado calibrado a 2mm para el estudio histomorfométrico. Se demostró que todos los animales irradiados sufrieron pérdida de peso 14 días después de ésta (p <0.05), independientemente de los tratamientos adicionales con dexametasona , siendo estadísticamente significativo. La histomorfometría mostró que el ancho máximo de la cápsula glomerular fue significativamente mayor en los grupos irradiados que en el control en p <0.05. El diámetro máximo del glomérulo fue significativamente mayor en los animales irradiados en comparación con los animales control p <0.05. Los resultados de este estudio mostraron que la administración intraperitoneal, de 1 mg / kg de peso corporal / día durante 2 días, de dexametasona antes de comenzar el tratamiento con irradiación, no impide la pérdida de peso ni permite aliviar el edema de los nefrones, injuria producto de la radiación a las Ratas Wistar.

Henoch-Schonlein purpura in children. Influence of age on the incidence of nephritis and arthritis

To assess the epidemiological, clinical, and laboratory findings in children affected with Henoch-Schonlein purpura [HSP], and to analyze the influence of age on the incidence of nephritis and arthritis. This is a retrospective study of the case records of all patients admitted to Prince Rahmah Hospital, Irbid, Jordan with HSP from September 1997 to December 2006, and to King Abdullah University Hospital, Irbid, Jordan from August 2005 to December 2006. The clinical manifestations included purpura in 100% of the 68 patients, arthritis in 75%, and nephritis in 29%. The incidence of nephritis varied according to the age of patients. It occurred in 19% of children less than 5 years of age, and in 67% of children 10 years of age and above. Henoch-Schonlein purpura nephritis was mild in all age groups. The incidence of arthritis also varied according to the age of patients. Arthritis occurred in 56% of children less than 5 years of age, and in 89% of children 10 years of age and above. The incidence of nephritis and arthritis in children affected with HSP is age related. Older children have a higher incidence of nephritis and arthritis, while younger children have a lower incidence of nephritis and arthritis. Renal involvement was mild during the acute phase of the disease in all age groups

Envolvimento renal na púrpura de Henoch-Schõnlein: uma análise multivariada de fatores prognósticos iniciais / Renal involvement in Henoch-Schõnlein purpura: a multivariate analysis of initial prognostic factors

OBJETIVOS: Identificar fatores preditivos iniciais de envolvimento renal nas crianças e adolescentes com púrpura de Henoch-Schõnlein. MÉTODOS: Por um período de 21 anos, os prontuários de 142 pacientes com diagnóstico de púrpura de Henoch-Schõnlein admitidos em nosso Hospital Universitário foram revistos. Os fatores preditivos iniciais avaliados nos primeiros 3 meses incluíram: dados demográficos, manifestações clínicas (púrpura palpável persistente, artrite, dor abdominal, dor abdominal intensa, sangramento gastrointestinal, orquite, envolvimento do sistema nervoso central e hemorragia pulmonar), exames laboratoriais (níveis séricos de IgA) e tratamento utilizado (corticosteróides, imunoglobulina endovenosa e medicação imunossupressora). Os pacientes foram divididos em dois grupos (com presença ou ausência de nefrite) e avaliados de acordo com a análise univariada e multivariada. RESULTADOS: Nefrite foi evidenciada em 70 pacientes (49,3 por cento). A análise univariada revelou que dor abdominal intensa (p = 0,0049; OR = 1,6; IC95 por cento 1,18-2,21), sangramento gastrointestinal (p = 0,004; OR = 1,6; IC95 por cento 1,10-2,26) e uso dos corticosteróides (p = 0,0012; OR = 1,7; IC95 por cento 1,28-2,40) foram associados com uma maior incidência de envolvimento renal. Na análise multivariada, a regressão logística mostrou que a única variável independente na predição da ocorrência de nefrite foi dor abdominal intensa (p < 0,012; OR = 2,593; IC95 por cento 1,234-5,452). CONCLUSÕES: Dor abdominal intensa representou um preditor significativo da nefrite na púrpura de Henoch-Schõnlein. Conseqüentemente, os pacientes pediátricos com esta manifestação clínica devem ser rigorosamente seguidos, devido ao maior risco de acometimento renal.

OBJECTIVES: To identify initial predictive factors of renal involvement in children and adolescents with Henoch-Schõnlein purpura. METHODS: We reviewed the medical records of 142 patients admitted to our University Hospital over a 21-year period with a diagnosis of Henoch-Schõnlein purpura. The initial predictive factors assessed, observed during the first 3 months, included: demographic data, clinical manifestations (persistent palpable purpura, arthritis, abdominal pain, severe abdominal pain, gastrointestinal bleeding, orchitis, central nervous system involvement and pulmonary hemorrhage), laboratory tests (serum IgA levels) and treatment given (corticosteroids, intravenous immunoglobulin and immunosuppressive drugs). Patients were divided into two groups (presence or absence of nephritis) and assessed by univariate and multivariate analysis. RESULTS: Evidence of nephritis was detected in 70 patients (49.3 percent). The univariate analysis revealed that severe abdominal pain (p = 0.0049; OR = 1.6; 95 percentCI 1.18-2.21), gastrointestinal bleeding (p = 0.004; OR = 1.6; 95 percentCI 1.10-2.26) and corticosteroid use (p = 0.0012; OR = 1.7; 95 percentCI 1.28-2.40) were all associated with increased incidence of renal involvement. In the multivariate analysis, logistic regression demonstrated that the only independent variable that predicted nephritis was intense abdominal pain (p < 0.012; OR = 2.593; 95 percentCI 1.234-5.452). CONCLUSIONS: Severe abdominal pain was a significant predictor of nephritis in Henoch-Schõnlein purpura. Consequently, pediatric patients exhibiting this clinical manifestation should be rigorously monitored, due to the increased risk of renal involvement.

ANA-negative SLE presenting with nephritis and oculomotor palsy--a case report.

Most large series of patients with systemic lupus erythematosus (SLE) have revealed a very small group of patients who are persistently antinuclear antibody (ANA) negative with prominent dermatologic involvement but infrequent neurological and renal involvement. We present a very unusual case report of a young female with ANA-negative SLE presenting with lupus nephritis and oculomotor palsy without any dermatologic manifestations.

A case of shunt nephritis

Nephritis associated with a chronically infected ventriculoatrial shunt is known as shunt nephritis. A 6-year-old girl with prior history of a ventriculoatrial shunt presented complaining of fever and gross hematuria. Serum complement levels were decreased and a coagulase-negative S. epidermidis was cultured from her blood. The renal biopsy specimen showed features of membranoproliferative glomerulonephritis type I. Hydrocephalus was so severe that shunt removal was impossible. With antibiotic therapy, clinical symptoms and laboratory findings include complement levels were normalized although microscopic hematuria persisted. To our knowledge, this is the first case of shunt nephritis in Korea. In addition to the case report, a brief review of shunt nephritis has been added.

Henoch-Schonlein syndrome in northern Indian children.

In order to evaluate clinical features and renal pathological findings of Henoch-Schonlein syndrome (HSS) in northern Indian Children, we studied 47 such cases. The mean age at onset was 8.5 yr; sex ratio (M:F) 2.6:1. The clinical features were purpuric rash (96%), abdominal pain (64%), Henoch-Schonlein nephritis (51%) and arthralgias (47%). Patients younger than 6 yr also showed urticarial rash or edema of scalp and extremities. Henoch-Schonlein nephritis (HSN) and abdominal symptoms were more common in older cases. The manifestations of HSN were asymptomatic hematuria and/or proteinuria (n = 15), acute nephritic syndrome (n = 6), and nephrotic syndrome (n = 3). The severity of clinical manifestations correlated with the renal pathologic findings. On follow up, 29% cases showed renal impairment. The prognosis was poor in patients with the acute nephritic or nephrotic syndrome and crescents in more than 50% glomeruli. Combination of clinical data and renal biopsy findings are important in assessing the long-term outcome in cases with HSN.

Nefritis lúpica, correlación clínico-histológica en 90 casos / Lupic nephritis, clinico-histological correlation in 90 cases

Las lesiones renales en el Lupus Eritematoso Sistémico (LES) han sido descriptas desde hace varios años y son origen de algunas de las distintas manifestaciones que configuran el polifacético cuadro dlínico de esta enfermedad. La referida patología nefrológica se presentó con una frecuencia variable, para las distintas experiencias publicadas. Los resultados obtenidos en los estudios realizados, tanto desde el punto de vista evolutivo como terapéutico han sido motivo de prolongadas discusiones. Con la intención de aportar un nuevo material casuístico, hemos reunido y analizado nuestra experiencia en los últimos años. De esta manera queremos plantear y establecer algunas conclusiones y discutir a la vez, los criterios dominantes en la actualidad

Nefritis postestreptocócica en pediatría: experiencia en 45 casos / Post-streptococcal nephritis in pediatrics: experience in 45 cases

Se analizan 45 casos de nefritis postestreptocócica observados durante 1983, destacando: a) un marcado incremento de casos concordante con el mayor número de consultas por escabiosis infectada; b) la evolución favorable del cuadro con menor permanencia hospitalaria, y c) la utilidad de la determinación de C3. Se resaltan los aspectos clínicos importantes