A new combination of naringin and trimetazidine protect kidney Mitochondria dysfunction induced by renal Ischemia / Reperfusion injury in rat

Abstract Ischemia/reperfusion (IR) injury leads to overproduction of Reactive Oxygen Species (ROS), and disrupts membrane potential that contributes to cell death. The aim of this study was to determine if naringin (NAR), trimetazidine (TMZ) or their combination, protect the kidney mitochondrial from IR injury. Forty rats were randomly allocated into five groups, harboring eight rats each: Sham, IR, NAR (100 mg/kg), TMZ (5 mg/kg) and NAR plus TMZ. Ischemia was induced by obstructing both renal pedicles for 45 min, followed by reperfusion for 4 hours. The mitochondria were isolated to examine the ROS, Malondialdehyde (MDA), Glutathione (GSH), mitochondrial membrane potential (MMP) and mitochondrial viability (MTT). Our findings indicated that IR injury resulted in excessive ROS production, increased MDA levels and decreased GSH, MMP and MMT levels. However, NAR, TMZ or their combination reversed these changes. Interestingly, a higher protection was noted with the combination of both, compared to each drug alone. We speculate that this combination demonstrates a promising process for controlling renal failure, especially with the poor clinical outcome, acquired with NAR alone. This study revealed that pretreatment their combination serves as a promising compound against oxidative stress, leading to suppression of mitochondrial stress pathway and elevation of GSH level.

Estimated glomerular filtration rate and drug dose adjustment in patients in an intensive care unit in Brazil

Objectives. This study sought to compare the estimated glomerular filtration rate and the indication of dose adjustment of antimicrobials when using Cockcroft-Gault or Modification of Diet in Renal Disease. Methods. A cross-sectional study was performed with patients admitted to the intensive care unit of a Brazilian general hospital. The glomerular filtration rate was calculated for patients on all days using the Cockcroft-Gault and Modification of Diet in Renal Disease equations. The difference in estimated glomerular filtration and the dose adjustment indication of antimicrobials were assessed. Results. A total of 631 patients were included in this study. The median estimated glomerular filtration was significantly higher when estimated using Modification of Diet in Renal Disease (100.3 mL/ min/1.73 m2) than the estimation by Cockcroft-Gault (83.2 mL/min) [p<0.001]. Greater differences in estimations produced by the two formulae were observed in patients at extremes of weight and age, and a different dose adjustment was indicated for all antimicrobials assessed. Conclusions. These results demonstrate a significant difference in estimated glomerular filtration rate values when calculated using either Cockcroft-Gault or Modification of Diet in Renal Disease as well as in the indication of dose adjustment in an intensive care unit

The effect of tadalafil therapy on kidney damage caused by sepsis in a polymicrobial septic model induced in rats: a biochemical and histopathological study

ABSTRACT Introduction Sepsis is an inflammatory reaction to bacteria involving the whole body and is a significant cause of mortality and economic costs. The purpose of this research was to determine whether tadalafil exhibits a preventive effect on sepsis in a septic model induced in rats with cecal ligation and puncture (CLP). Materials and Methods Rats were randomly separated into groups, 10 rats in each: (i) a sham (control) group, (ii) an untreated sepsis group, (iii) a sepsis group treated with 5mg/kg tadalafil and (iv) a sepsis group treated with 10mg/kg tadalafil. A polymicrobial sepsis model was induced in rats using CLP. Rats were sacrificed after 16h, and blood and kidney tissues were collected for biochemical and histopathological study. Results Levels of the inflammatory parameter IL-6 decreased significantly in the sepsis groups receiving tadalafil in comparison with the untreated sepsis group (p<0.05). In terms of histopathology, inflammation scores investigated in kidney tissues decreased significantly in the sepsis groups receiving tadalafil compared to the untreated sepsis group (p<0.05). In addition, levels of creatinine and cystatin C measured in septic rats receiving tadalafil were lower by a clear degree than in septic rats (p<0.05). Conclusion In this study, tadalafil exhibited a preventive effect for sepsis-related damage by suppressing inflammation in serum and kidney tissue of septic rats in a polymicrobial sepsis model induced with CLP.

Protective effect of hydrogen sulfide on renal injury in the experimental unilateral ureteral obstruction

Introduction/Objective: Ureteral obstruction is a common pathology and causes kidney fibrosis and dysfunction at late period. In this present study, we investigated the antifibrotic and antiinflammatory effects of hydrogen sulfide on kidney damage after unilateral ureteral obstruction (UUO) in rats. Materials and Methods: 24 rats were divided into four groups. Group 1 was control, group 2 was sham, group 3 included rats with UUO and group 4 rats with UUO which were given sodium hydrogen sulfide (NaHS)-exogenous donor of hydrogen sulfide (intraperitoneally 56μmoL/kg/day). After 14 days, rats were killed and their kidneys were taken and blood analysis was performed. Tubular necrosis, mononuclear cell infiltration and interstitial fibrosis were determined histopathologically in a part of the kidneys; nitric oxide (NO), malondialdehyde (MDA) and reduced glutathione (GSH) levels were determined in the other part of the kidneys. Urea-creatinine levels were investigated by blood analysis. Statistical analyses were made by the Chi-square test and one-way analysis of variance (ANOVA). Results: There was no significantly difference for urea-creatinine levels among groups. Pathologically, there was serious tubular necrosis and fibrosis in group 3 and there was significantly decreasing of tubular necrosis and fibrosis in group 4 (p<0.005). Also, there was significantly increase of NO and MDA levels and decrease of GSH levels in group 3 compared to other groups (p<0.005). Conclusions: hydrogen sulfide prevents kidney damage with antioxidant and antiinflammatory effect.

Cirrhosis inducss apoptosis in renal tissue through intracellular oxidative stress / Cirrose induz apoptose em tecido renal através de estresse oxidativo intracelular

Background Renal failure is a frequent and serious complication in patients with decompensated cirrhosis. Objectives We aimed to evaluate the renal oxidative stress, cell damage and impaired cell function in animal model of cirrhosis. Methods Secondary biliary cirrhosis was induced in rats by ligation of the common bile duct. We measured TBARS, ROS and mitochondrial membrane potential in kidney as markers of oxidative stress, and activities of the antioxidant enzymes. Relative cell viability was determined by trypan blue dye-exclusion assay. Annexin V-PE was used with a vital dye, 7-AAD, to distinguish apoptotic from necrotic cells and comet assay was used for determined DNA integrity in single cells. Results In bile duct ligation animals there was significant increase in the kidney lipoperoxidation and an increase of the level of intracellular ROS. There was too an increase in the activity of all antioxidant enzymes evaluated in the kidney. The percentage viability was above 90% in the control group and in bile duct ligation was 64.66% and the dominant cell death type was apoptosis. DNA damage was observed in the bile duct ligation. There was a decreased in the mitochondrial membrane potential from 71.40% ± 6.35% to 34.48% ± 11.40% in bile duct ligation. Conclusions These results indicate that intracellular increase of ROS cause damage in the DNA and apoptosis getting worse the renal function in cirrhosis. .

Contexto A falência renal é uma complicação grave e frequente em pacientes com cirrose descompensada. Objetivo Avaliar o estresse oxidativo, o dano ao DNA e alterações na função celular no rim em um modelo animal de cirrose. Métodos A cirrose biliar secundária foi induzida em ratos através da ligadura do duto biliar comum. Foi medido no rim o TBARS (substâncias que reagem ao ácido tiobarbitúrico), ERO (espécies reativas de oxigênio), o potencial de membrana mitocondrial e a atividade das enzimas antioxidantes. A viabilidade celular foi determinada utilizando o ensaio de exclusão do trypan-blue. Para distinguir células em apoptose ou necrose foram usados os marcadores: Anexina V-PE e 7-AAD e o ensaio cometa foi utilizado para determinar dano ao DNA. Resultados Em animais cirróticos houve um aumento significativo da lipoperoxidação no rim e na quantidade de ERO intracelular. Foi observado um aumento na atividade de todas as enzimas antioxidantes. A porcentagem de viabilidade celular foi superior a 90% no grupo controle e de 64,66% no grupo da ligadura do duto biliar. O padrão de morte celular predominante foi apoptose e houve dano ao DNA no grupo da ligadura do duto biliar. Observou-se uma redução no potencial de membrana mitocondrial no grupo da ligadura do duto biliar (34,48% ± 11,40%) em comparação aos controles (71,40% ± 6,35%). Conclusão Esses resultados parecem indicar que nos animais cirróticos ocorre um aumento no dano oxidativo e ao DNA levando as células renais à apoptose, o que contribui para a falência renal na cirrose. .

Esclerosis sistémica y daño renal / Systemic sclerosis and renal damage

La afección renal es infrecuente en la esclerosis sistémica, pero constituye una complicación grave que ocurre más frecuentemente en la forma clínica difusa. Se describe el comportamiento de una paciente con esclerosis sistémica difusa que desarrolla una hipertensión arterial refractaria complicada, anemia y falla renal. Se realizó biopsia renal con una descripción histopatológica compatible con una nefropatía isquémica asociada a la enfermedad con un mal pronóstico, a pesar del tratamiento con inhibidores de la enzima de conversión de angiotensina

Renal disease is uncommon in systemic sclerosis but, at the same time, it is a severe complication occurring more frequently in a diffuse clinical form. The behavior of a female patient with diffuse systemic sclerosis that developed a complicated refractory arterial hypertension, anemia and renal failure is described. Renal biopsy was made with a histopathological description consistent with an ischemic kidney disease associated with this disease which had a poor prognosis despite the treatment with angiotensin converting enzyme inhibitors

Biopsia renal en el segundo trimestre del embarazo: Dos casos clínicos / Renal biopsies during the second trimester of pregnancy: Report of two cases

Kidney biopsies were performed in two women during their 21th and 24th week of pregnancy. The first patient developed an abrupt nephrotic syndrome without hypertension or kidney failure. The pathological study disclosed diffuse podocyte alterations such as those observed in focal and segmental glomerulosclerosis, which had a good response to steroidal treatment. The second patient had a progressive renal failure associated with non-nephrotic proteinuria. The biopsy disclosed a fibrillary glomerulopathy.

Probable chronic renal failure caused by Lonomia caterpillar envenomation

Erucism is a skin reaction to envenomation from certain poisonous caterpillar bristles. In Brazil, most reports of erucism provoked by Lonomia caterpillars are from the southern region. Most manifestations of erucism are local and include burning pain, itching, local hyperthermia and, rarely, blisters (benign symptoms with spontaneous regression in a few hours). General symptoms such as nausea and vomiting, headache, fever, myalgia, abdominal pain and conjunctivitis may also occur. Uncommon symptoms include arthritis, coagulation disorders (manifested as bruising and bleeding), intracerebral hemorrhage and acute renal failure, which comprise serious complications. The present study reports the case of 60-year-old patient from Rio de Janeiro state, Brazil, who came into contact with a caterpillar and developed, a few days later, chronic renal disease.

Bloqueio atrioventricular adquirido por uso de amiodarona: relato de caso / Atrioventricular block induced by amiodarone therapy: case report

JUSTIFICATIVA E OBJETIVOS: A amiodarona é um antiarrítmicoda classe III, amplamente utilizado nas mais diversas arritmias. Entretanto, a despeito de seus benefícios hemodinâmicos e eletrofisiológicos, ela produz efeitos colaterais relevantes, como coloração azulada da pele, fotossensibilidade,disfunção tireoidiana, depósito corneal, neuropatia periférica, supressão da medula óssea, hepatite, bloqueios cardíacos, pneumonites e outros. Os principais efeitos colaterais cardíacos, após terapia prolongada com amiodarona são: bradicardia sinusal, observada mais frequentemente e,menos comumente, bloqueio atrioventricular (BAV). O objetivo deste estudo foi relatar um caso de BAV por uso de amiodarona.RELATO DO CASO: Paciente do sexo masculino, 73 anos, negro,portador de insuficiência renal crônica dialítica, encaminhado para internação com história de inapetência, vômitos, emagrecimento e dor abdominal, além de bradicardia assintomática. No eletrocardiograma (ECG) observou-se bloqueio atrioventricular total (BAVT). Após a suspensão dos fármacos utilizados, os sintomas desapareceram em seis dias. CONCLUSÃO: Pacientes em uso inadvertido e prolongado de alguns fármacos devem ser com frequência reavaliados, clinica e laboratorialmente, pois níveis acima da janela terapêutica só serão descobertos desta forma, na ausência de sintomatologia.(AU)

BACKGROUND AND OBJECTIVES: Amiodarone is a class III antiarrhythmic, widely used in a variety of arrhythmias. However, despite its hemodynamic and electrophysiological benefits,amiodarone produces serious collateral effects such as blue skin coloration, photosensitivity, thyroid dysfunction, corneal deposits,peripheral neuropathy, bone marrow suppression, hepatitis,heart blocks, pneumonitis and other. The main cardiac side effects after prolonged therapy with amiodarone are bradycardia,observed more frequently and less commonly, atrioventricular block. The objective of this study is to report a case of atrioventricular block due to use of amiodarone.CASE REPORT: Male, year 73, a black patient with chronic renal failure, referred to internation, with history of innapetency,vomiting, weight loss and abdominal pain and also asymptomatic bradycardia. On EKG there was an atrioventricular block. After discontinuation of the drug, the symptoms disappeared in 6 days.CONCLUSION: Patients on inappropriate use of some drugs,mainly long-term, should be frequently reassessed, so clinical and laboratory, because levels above the therapeutic window only this way will be discovered, in absence of symptoms.(AU)

Multiple myeloma presenting as collapsing glomerulopathy.

A 54 year old male patient was admitted with advanced renal failure of recent onset. Serology was noncontributory. Renal biopsy showed collapsing glomerulopathy with interstitial fibrosis. Bone marrow examination confirmed the diagnosis of multiple myeloma. With chemotherapy multiple myeloma went into remission. However he continued to remain dialysis dependent and a repeat kidney biopsy showed progression to endstage renal disease.

The renal pathology in children dying with hepatic cirrhosis.

The aim of this analysis was to observe the pathologic changes in the kidney in 23 children dying of cirrhosis, including five children with renal failure. Besides these pathologic changes, glomerular cellularity and arteriolar wall thickness of these patients were compared with 18 age matched autopsy controls dying of nonhepatic and nonrenal causes. Histologic examination of the kidneys in these cirrhotic children showed significant tubular changes in five patients, diffuse glomerulosclerosis in five, only one child had membranous glomerulopathy or glomerulonephritis and one cirrhotic with serum hepatitis B surface antigen positivity had polyarteritis nodosa. No statistically significant changes were observed in the glomerular cellularity and the arteriolar wall thickness in these cirrhotic children as compared to the controls. However, medial proliferation and hyaline arteriolosclerosis were observed in four cirrhotic children. Tubular bile casts and nephrocalcinosis were the sole lesions causing renal failure in two cases. A combination of glomerulosclerosis, cast formation and arteriolosclerosis was seen in the remaining three patients. Thus the kidney showed a spectrum of pathology in pediatric cirrhosis. The tubular lesions causing renal failure represent acute treatable lesions whereas glomerulosclerosis and arteriosclerosis stand for a more chronic and less reversible renal damage.

Systemic amyloidosis in Hodgkin's disease.

Secondary amyloidosis as a complication of Hodgkin's disease has been described as being unusual to rare in occurrence. We report a case in which the clinical picture was that of a renal failure, etiology of which could not be determined but which proved to be amyloidosis secondary to clinically unrecognised Hodgkin's disease.

Primary hyperoxaluria: report of four cases and review of the literature

In this paper we will present four cases of primary hyperoxaluria. All patients had a significant past medical history of polyuria [with or without microscopic hematuria] and polydypsia. All patients had a family history of their parents being cousins. Initial evaluation of all patients by ultrasound and plain abdominal films revealed nephrocalcinosis. Their clinical courses showed gradual loss of renal function over the follow-up years. We will also review primary hyperoxalurias and their management in this report

Falciparum malaria: an uncommon cause of acute renal failure in Saudi Arabia: a case report and review

A successfully treated case of severe falciparum malaria presenting with acute renal failure [ARF] and jaundice, is reported. Despite the fact that ARF is a common complication of severe falciparum infection, there has been no report of such a complication from Saudi Arabia up to the present time. Discussion on the pathophysiology of renal lesions and treatment is presented. High index of suspicion is required in non endemic areas for malaria, for rapid and correct diagnosis and treatment of a treatable otherwise fatal condition

Lesäo hepatica na insuficiência renal mioglobinurica (rabdomiolise): estudo experimental em ratos / Hepatic dysfunction in myoglobinuric acute renal failure: experimental study in rats

A possivel relaçäo causal entre insuficiência renal mioglobinurica (rabdomiolise) e lesäo hepatica ainda nao esta bem definida e foi objeto deste estudo. Ratos machos (220-270 g) foram privados de agua por 24 horas e divididos em dois grupos: GI-animais experimentais em que a rabdomiolise foi induzida mediante injeçäo intramuscular de glicerol a 50 por cento na dose de 10 ml/kg. GII-animais controles que receberam injecao intramuscular de solucao salina. Vinte e quatro horas apos a injecao todos os animais foram sacrificados. No sangue colhido foram dosados AST, ALT, CK, ureia e creatinina. Os figados foram removidos para estudo histologico e para avaliacao da funcao mitocondrial, determinada polarograficamente com eletrodo de Clark, medindo-se o consumo de oxigenio na ausencia de ADP (S4-Basal) e na presenca de ADP (S3-Ativado). A razao do controle respiratorio (RCR) e relacao ADP/O foram calculadas...

Anticuerpos anti-VHC en insuficientes renales crónicos / Anti-HCV antibodies in patients with chronic renal failure

El virus de la hepatitis C es la principal causa de hepatitis post-transfusional en el mundo, pero poco se conoce acerca de la transmisión en los pacientes con insuficiencia renal crónica y en las unidades de hemodialisis. El presente trabajo estimó la prevalencia de los anticuerpos anti-VHC en los pacientes con insuficiencia renal crónica del Departamento de Nefrología del Hospital Universitario de los Andes, en Mérida Venezuela. Se admitieron 22 pacientes al estudio, todos con insuficiencia renal crónica. Los datos médicos referentes a factores de riesgo (trasnfuciones, drogadicción y promiscuidad sexual) fueron obtenidos de las historias clínicas y las encuestas aplicadas a los pacientes. Un ELISA anti-VHC de segunda generación fue usado como prueba serológica. De los 22 pacientes estudiados, 5 fueron anti-VHC positivos y 17 fueron negativos. Los 5 pacientes seropositivos eran hemodializados, lo cual arrojó una prevalencia del 22,7 por ciento en el grupo de estudio. Todos los pacientes insuficientes renales crónicos no hemodializados fueron anti-VHC (p= 0.0047). No hubo asociación significativa entre transfuciones y positividad al anti-VHC (p= 0.36). La hemodiálisis podría ser un factor de riesgo en la trasmisión del virus de la hepatitis C

Pathologie aigue et fonction renale : a propos de 322 observations au C.H.N.U. de Cotonou

Pendant une periode de 5 ans; les deux unites qui constituent le Service Polyvalent de Reanimation du CHNU de Cotonou ont admis 4937 patients dont 680 ont presente une insuffisance renale aigue soit une prevalence de 13;57 pour cent. Analysant 322 dossiers les auteurs ont tire plusieurs conclusions. L'insuffisance renale aigue est plus frequente dans le secteur chirurgical que dans le secteur medical. Elle frappe des sujets jeunes avec un sex-ratio de 2 hommes pour une femme. Les principales etiologies sont: abdomen chirurgical aigu (peritonites et occlusion en tete); traumatologie; urologie; obstetrique et dans le secteur medical: l'insuffisance renale aigue; les intoxications medicamenteuses; le paludisme complique et le choc septique. L'hypercreatinemie varie de 139 a 3161 mmoles/litres. L'hyperkaliemie n'est pas exceptionelle (29 cas) comme l'hyponatremie (81 cas) et l'hypocalcemie (26 cas). L'insuffisance renale aigue est le type le plus frequent en milieu chirugical (95 pour cent des cas) alors que la forme organique est dominante dans le secteur medical. Le traitement symptomatique utilise le remplissage vasculaire (199 fois); le Furosemide (206 fois); la Dopamine a dose dopaminergique (77 fois); l'alcalinisation (112 fois) et l'hemodialyse (39 fois). Le traitement etiologique est base sur la chirurgie; la malariatherapie; l'antibiotherapie; la prise en charge des intoxications aigues. La mortalite globale a ete tres elevee (40;06 pour cent) plus forte dans le secteur medical (45;79 pour cent) qu'en milieu chirurgical

Previene la octreótida el daño renal por isquemia y reperfusión? / Prevents octreotide the renal damage caused by ischemia and reperfusion?

La finalidad de este estudio fue valorar la utilidad de la octreótida para la prevención del daño renal por isquemia y reperfusión. Con esta finalidad se realizó un estudio experimental con 26 ratas Sprague Dawley, con las que se formaron tres grupos: el grupo A normal sin isquemia renal, el grupo B con isquemia sin tratamiento, y el grupo C con isquemia y con octreótida que se administró siete días del suceso isquémico a la dosis de 100 µg/m2 por vía subcutánea. Se realizó laparotomía y se identificaron ambas arterias renales, tras lo cual se produjo isquemia durante 40 minutos. Al finalizar este plazo se retiraron las pinzas vasculares y se reperfundió el riñón durante 30 minutos. Se tomó una muestra de sangre para analizar las concentraciones de creatinina, y se realizó nefroureterectomía bilateral para estudio histopatológico y para valorar el daño renal. En el grupo testigo la creatinina promedio fue de 34.3 µmol/dL, y el estudio de histopatología no demostró lesión. En el grupo B se encontró elevación de la creatinina en cinco ratas, y en el C esto sucedió sólo en una (p < 0.14). El daño histológico fue menor en el grupo C y mayor en el B (sin octreótida) (p < 0.03). Cabe concluir que la octreótida puede ser útil para la prevención del daño renal por isquemia y reperfusión

Afectación renal en el síndrome onico-patelar / Renal involvement in the onycho-patellar syndrome

El síndrome onico-patelar es un cuadro genético autosómico dominante con una expresividad variable que afecta tejido de origen ectodérmico y mesodérmico. Es poco frecuente y se caracteriza por una tetrada: alteraciones ungueales, lúnula triangular, rótula hipoplásica o ausente, artrodisplasia de codo y cuernos ilíacos. Motiva esta presentación la observación de pacientes con afectación renal, haciendo una revisión bibliográfica en este sentido