Ameliorating effects of ethanol extract of root bark of Salacia nitida on blood electrolyte and renal perturbations in Plasmodium berghei-infected mice

Abstract Malaria, a disease of public health concern is a known cause of kidney failure, and dependence on herbal medicines for its treatment is increasing due to the high cost of drugs. So this study is designed to evaluate the ameliorating effect of ethanol extract from Salacia nitida root bark on electrolyte and renal perturbations in Plasmodium berghei-infected mice. Thirty malariainfected mice divided into five groups of six mice each and another group of six uninfected mice were used for the study. 280, 430, and 580 mg/kg of extract were given to infected mice in groups B, C, and D, 4 mg/kg of artesunate given to group E mice, and 4 ml/kg of physiological saline given to group A and uninfected group F mice for five days. Serum Na+, K+, HCO3, Cl-, TB, urea, creatinine, BUN concentrations, and BUN/creatinine ratio were determined using standard methods. Results showed significant increases (p < 0.05) in Na+, K+, and HCO3 and decreases in Cl-, TB, urea, creatinine, BUN, and BUN/creatinine ratio in the infected treated mice in groups B - E. This study showed that ethanol extract of S. nitida root bark is efficient in the treatment of renal disorders and blood electrolyte perturbations

Infección letal por adenovirus: presentación de un caso / Lethal infection for adenovirus: case report

Adenovirus (ADV) can cause serious, localized or disseminated, sometimes lethal disease. There is no specific treatment, only support management according to requirements and severity of disease. Extracorporeal membrane oxygenation (ECMO) has been used in severe ADV infection. Cidofovir has been reported as a therapeutic option. This case reports a lethal case of ADV respiratory infection despite the treatment with cidofovir an ECMO.

El adenovirus (ADV) puede causar infección respiratoria grave, localizada o diseminada y letal en pacientes susceptibles. No existe terapia específica, solo de soporte según requerimientos y gravedad. En este sentido el manejo con oxigenación por membrana extracorpórea (ECMO) ha sido utilizado en niños con infección grave por ADV. Si bien no existe terapia específica actual se ha reportado uso de cidofovir que ha ganado espacio como posibilidad terapéutica en caso de enfermedad grave. Se presenta el caso clínico de un paciente que cursó con infección letal por ADV a pesar del tratamiento de soporte con ECMO y el tratamiento con cidofovir.

Hepatotoxicidad por esteroides anabólicos androgénicos, reporte de 2 casos en Uruguay / Hepatotoxicity induced by anabolic-androgenic steroids, 2 cases report in Uruguay / Hepatotoxicidade por anabolizantes esteróides androgênicos, relato de 2 casos no Uruguai

El consumo ilícito de esteroides anabólicos androgénicos con fines estéticos ha aumentado en los últimos años y, aunque raro, es causa de hepatotoxicidad. Los casos con daño hepatocelular son más frecuentes, pero los colestásicos son más graves y pueden asociarse a falla renal. Salvo por la suspensión del fármaco, la hepatotoxicidad por anabólicos no tiene tratamiento específico. Se describe y discuten las historias clínicas de dos hombres jóvenes, deportistas aficionados que consultaron por ictericia y presentaron colestasis e insuficiencia renal. El reporte de casos, en patologías poco frecuentes, resulta fundamental para difundir y ampliar la información que ayude al clínico a considerar con firmeza este diagnóstico, incluso ante la falta de reconocimiento inicial del consumo por parte del paciente.

Illicit consumption of anabolic-androgenic steroids for aesthetic purposes has increased in recent years. Hepatocellular damage is more frequent, but cholestasis is more dangerous and may be associated with renal failure. The clinical records of two young men, amateur athletes who consulted for jaundice in the last year and denied its consumption at the beginning, are described. Except for the drug interruption, hepatotoxicity by anabolics has no specific treatment. Usually presented as cholestatic liver disease and renal failure, case reports are fundamental to characterize its clinical-evolutionary presentation. This may also allow clinicians to firmly consider diagnosis even when the patient denies consumption.

O uso ilícito de esteróides androgênicos anabólicos para fins estéticos tem aumentado nos últimos anos e, apesar de raro, é causa de hepatotoxicidade. Casos com dano hepatocelular são mais freqüentes, mas colestesia é mais grave e pode estar associada à insuficiência renal. Com exceção da suspensão do medicamento, a hepatotoxicidade anabólica não possui tratamento específico. As histórias clínicas de dois homens jovens, atletas amadores que consultaram para icterícia e apresentaram colestase e insuficiência renal, são descritos e discutidos. O relato de casos, em patologias pouco freqüentes, é fundamental para disseminar e ampliar as informações que auxiliam o clínico a considerar com firmeza esse diagnóstico antes mesmo do não reconhecimento inicial do consumo pelo paciente.

The curative effects of methylsulfonylmethane against glycerol-induced acute renal failure in rats

Abstract The present study was performed to explore the curative effect of Methylsulfonylmethane (MSM) in an experimental model of myoglobinuric acute renal failure (ARF). In this experimental model, Rats were injected with 50% glycerol (10 mL/kg, im) followed by an hour later and daily in the next six days by MSM (400 mg/kg) or saline. Kidney's function (urea and creatinine), and reduced glutathione were analyzed. A renal failure produced by glycerol injection, with a significant increase of blood urea and serum creatinine was observed. Rats that received MSM in addition to glycerol had significantly lower blood urea and serum creatinine levels compared to those receiving glycerol alone. However, glutathione has markedly increased after MSM treatment. The effect is probably due to the antioxidant activity of MSM. This may provide therapeutic opportunities for treating humans, myoglobinuric ARF.

Plomo y nefropatía: biomarcadores urinarios en la detección de daño renal precoz / Blood lead levels and markers of renal dysfunction among mechanical workshop workers

The role of lead (Pb) as an environmental cause of nephropathy is difficult to ascertain due to the difficulty to determine clinically its exposure. Aim: To assess lead levels and renal function in a group of males working in mechanical workshops. Material and Methods: Blood and urine samples were obtained from 100 mechanical workshop workers aged 38 ± 16 years and 95 non-exposed office clerks aged 37 ± 17 years. Blood lead and creatinine levels were determined. In exposed workers, urinary excretion of intestinal alkaline phosphatases (IAP) and N-acetyl-glucosaminidase (NAG) were measured as early markers of renal failure. Results: Blood lead levels were 66.4 ± 43 and 33.6 ± 18 µg/L among mechanical workshop workers and non-exposed controls, respectively, p < 0.01. The figures for serum creatinine were 0.9 ± 0.1 and 0.9 ± 0.1 respectively, p = NS. Among exposed workers urinary excretion of IAP was 0.47 ± 0.6 U/L and of NAG, 0.92 ± 1.1 U/L. There was a positive correlation between blood lead levels and NAG excretion (r = 0.284) and IAP excretion (r = 0.346). Conclusions: Exposed workers had higher blood lead levels and there was a weak positive association between these levels and the urinary excretion of NAG and IAP.

Risks associated with sunitinib use and monitoring to improve patient outcomes

No abstract available.

Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea

BACKGROUND/AIMS: Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy. METHODS: We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months. RESULTS: One hundred and fifty-five patients (mean age, 58.7 +/- 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU. CONCLUSIONS: The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.

Imnunosupresión tras el trasplante hepático: más nefrones, menos hepatocarcinoma / Immunosupression after liver transplant: more nephrons, less hepatocellular carcinoma

Following liver transplantation, immunosuppressive drugs are responsible for a significant proportion of the morbidity and mortality. Thus, renal failure and hepatocellular carcinoma recurrence are critically related to the use of immunosuppressive drugs. In this article, the immunosuppressive strategies that allow preservation of the renal function and minimization of the recurrence rate of hepatocellular carcinoma are detailed.

Tras el trasplante hepático, la inmunosupresión es responsable de buena parte de la morbi-mortalidad asociada. El deterioro de la función renal y la recurrencia del hepatocarcinoma son ámbitos donde la inmunosupresión tiene un impacto significativo. En el presente artículo se abordan las estrategias inmunosupresoras que permiten preservar la función renal y minimizar la recurrencia del hepatocarcinoma tras el trasplante hepático.

Terapia com inibidor da ECA com dosagens relativamente altas e risco de agravamento renal na insuficiência cardíaca crônica / ACE-inhibitor therapy at relatively high doses and risk of renal worsening in chronic heart failure

FUNDAMENTO: O efeito renoprotetor dos inibidores da ECA vem sendo questionado no caso de diminuição do volume circulante efetivo, como na insuficiência cardíaca crônica direita ou biventricular. Objetivo: Detectar os preditores clínicos de agravamento renal na população de pacientes com ICC, caracterizado por dois tipos de regime de dosagem de inibidores da ECA. MÉTODOS: De acordo com um desenho de coorte retrospectiva, seguimos dois grupos de pacientes com ICC - tanto direita quanto biventricular -, todos na classe III da NYHA, tratados com inibidores da ECA (enalapril ou lisinopril), e com fração de ejeção do ventrículo esquerdo (FEVE) < 50 por cento, por meio de distinção em sua dosagem de inibidor da ECA: média-baixa (< 10 mg por dia) ou dosagem "alta" (> 10 mg por dia) de enalapril ou lisinopril. A disfunção renal agravada (ARD) foi definida pelo aumento de Cr > 30 por cento com relação ao segmento basal. O modelo de risco proporcional de Cox foi utilizado para identificar os preditores da ARD entre as seguintes variáveis: os inibidores da ECA com "alta" dosagem, idade, FEVE basal, histórico de repetidas terapias intensivas com diuréticos de alça por via intravenosa (diurético intravenoso), diabete, Cr basal, histórico de hipertensão, pressão arterial sistólica < 100 mmHg. RESULTADOS: Cinquenta e sete pacientes foram recrutados, dos quais 15 foram tratados com inibidor da ECA com dosagem "alta". Durante um seguimento médio de 718 dias, a ARD ocorreu em 17 pacientes (29,8 por cento). Apenas o inibidor da ECA com "alta" dosagem (RR: 12,4681 IC: 2,1614 - 71,9239 p = 0,0050) e Cr basal (RR:1,2344 IC: 1,0414 - 1,4632 p = 0,0157) foi demonstrado ser preditor da ARD. Além disso, demonstrou-se que o inibidor da ECA com dosagens "altas" não previu ARD em ICC sem diurético intravenoso e ICC com diabete. CONCLUSÃO: Na ICC de classe III da NYHA, o inibidor da ECA com "altas" dosagens e um maior Cr basal foi preditor da ARD. A nefrotoxicidade relacionada com inibidores da ECA em "altas" dosagens foi aumentada com o diurético intravenoso, ao passo que, em pacientes com ICC com diabete, aquela não foi detectada.

BACKGROUND: Renoprotective effect of ACE-inhibitors has been questioned in case of decreased effective circulating volume, like in right or biventricular chronic heart failure. OBJECTIVE: To detect clinical predictors of renal worsening in CHF patient population characterized by two types of ACE-inhibitor dosing regimens. METHODS: According to a retrospective cohort design, we followed 2 groups of patients with CHF - whether right or biventricular -, all in III NYHA class treated with ACE-inhibitors (enalapril or lisinopril), and with left ventricular ejection fraction (LVEF) < 50 percent, by distinguishing them by ACE-inhibitor dosing: average-low (<10 mg per day) or "high" dose (>10 mg per day) of enalapril or lisinopril. Worsened renal failure (ARD) was defined by Cr increase >30 percent from baseline. Cox proportional hazards model was used to identify the predictors of ARD among the following variables: ACE-inhibitors "high" dose, age, basal LVEF, history of repeated intensive intravenous loop diuretic therapies (IV diur), diabetes, basal Cr, history of hypertension, systolic blood pressure < 100 mm Hg. RESULTS: 57 patients were recruited, of whom 15 were treated with ACE-inhibitor "high" dose. During a mean follow-up of 718 days, ARD occurred in 17 (29.8 percent) patients. Only ACE-inhibitor "high" dose (HR: 12.4681 C.I.: 2.1614-71.9239 p=0.0050) and basal Cr (HR: 1.2344 C.I.: 1.0414-1.4632 p=0.0157) were shown to predict ARD. Moreover, ACE-inhibitor "high" doses were shown to fail to predict ARD in both CHF without IV diur and CHF with diabetes. CONCLUSION: In III NYHA class CHF, ACE-inhibitor "high" doses and a higher basal Cr predicted ARD. Nephrotoxicity related to ACE-inhibitor "high" doses was increased by IV diur, whereas it was not detected in CHF patients with diabetes.

Há uma associação entre anti-inflamatórios não-esteroides e nefropatia induzida por contraste? / Is there an association between non-steroidal anti-inflammatory drugs and contrast nephropathy? / ¿Hay una asociación entre antiinflamatorios no esteroides y nefropatía inducida por contraste?

FUNDAMENTO: A associação entre o uso de anti-inflamatórios não-esteroides (AINEs) e insuficiência renal aguda ou crônica é bem documentada, mas evidências sobre a associação entre AINEs e nefropatia induzida por contraste (NIC) não são encontradas na literatura. OBJETIVO: Avaliar uma possível associação entre AINEs e NIC. MÉTODOS: Em um estudo de coorte, através da entrevista clínica de pacientes que foram submetidos à cateterização cardíaca, analisamos o uso de AINEs e sua associação com desenvolvimento de NIC, através da alteração dos níveis de creatinina sérica ou taxa de filtração glomerular em 48 ou 72 horas. RESULTADOS: No período de julho de 2005 a julho de 2006, 236 pacientes foram incluídos no estudo, dos quais 29 foram posteriormente excluídos. A incidência de NIC foi 10,37 por cento (20 de 207) e 42 por cento dos pacientes estavam recebendo AINEs até o momento da avaliação. Não houve associação entre o uso de AINEs e o desenvolvimento de NIC com OR de 1,293; IC95 por cento (0,46-4,2). O estudo detectou fatores de risco conhecidos para o desenvolvimento de NIC, tais como diabete, com OR de 2,77; IC95 por cento (1,05-7,47) e insuficiência renal crônica com OR de 3,48; IC95 por cento (1,1-11,07) e também sugeriu uma ação protetora da hidratação com solução salina com OR de 0,166; IC95 por cento (0,03-0,92). CONCLUSÃO: Com base nos dados obtidos, concluímos que não houve associação entre NIC e uso prévio de AINEs, pelo menos com um OR > 2,85, o qual nossa amostra detectou.

BACKGROUND: The association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and acute or chronic renal failure is well documented, but evidence of such association between NSAIDs and Contrast-Induced Nephropathies (CIN) is not found in the indexed literature. OBJECTIVE: To evaluate the possible association between NSAIDs and CIN. METHODS: In a cohort study, through clinical interviews of patients that underwent cardiac catheterization, we analyzed the use of NSAIDs and its association with the development of CIN, through alterations in serum creatinine or glomerular filtration rate in 48 or 72 hours. RESULTS: From July 2005 to July 2006, 236 patients were enrolled in the study, of which 29 were later excluded. The incidence of CIN was 10.37 percent (20 of 207) and 42 percent of the patients were using NSAIDs until the moment of the evaluation. There was no association between the use of NSAIDs and the development of CIN with OR of 1.293 95 percent CI (0.46-4.2). The study detected known risk factors for the development of CIN, such as diabetes with OR of 2.77 95 percentCI (1.05-7.47) and chronic renal failure with OR 3.48 95 percentCI (1.1-11.07). A protective action of saline solution hydrationis also suggested, with OR of 0.166 95 percentCI (0.03-0.92). CONCLUSION: Based on the data obtained, we conclude that there was no association between CIN and previous use of NSAIDs, at least with an OR higher then 2.85, which our sample detected.

FUNDAMENTO: La asociación entre el uso de antiinflamatorios no esteroides (AINEs) e insuficiencia renal aguda o crónica está bien documentada, pero evidencias sobre la asociación entre AINEs y nefropatía inducida por contraste (NIC) no son encontradas en la literatura. OBJETIVO: Evaluar una posible asociación entre AINEs y NIC. MÉTODOS: En un estudio de cohorte, a través de la entrevista clínica de pacientes que fueron sometidos a cateterismo cardíaco, analizamos el uso de AINEs y su asociación con desarrollo de NIC, a través de la alteración de los niveles de creatinina sérica o tasa de filtrado glomerular en 48 o 72 horas. RESULTADOS: En el período de julio de 2005 a julio de 2006, 236 pacientes fueron incluidos en el estudio, de los cuales 29 fueron posteriormente excluidos. La incidencia de NIC fue 10,37 por ciento (20 de 207) y 42 por ciento de los pacientes estaban recibiendo AINEs hasta el momento de la evaluación. No hubo asociación entre el uso de AINEs y el desarrollo de NIC con OR de 1,293; IC95 por ciento (0,46-4,2). El estudio detectó factores de riesgo conocidos para el desarrollo de NIC, tales como diabetes, con OR de 2,77; IC95 por ciento (1,05-7,47) e insuficiencia renal crónica con OR de 3,48; IC95 por ciento (1,1-11,07) y también sugirió una acción protectora de la hidratación con solución salina con OR de 0,166; IC95 por ciento (0,03-0,92). CONCLUSIÓN: Con base en los datos obtenidos, concluimos que no hubo asociación entre NIC y uso previo de AINEs, por lo menos con un OR > 2,85, el cual nuestra muestra detectó.

Drogas nefrotóxicas / Drug-induced nephrotoxicity

La estructura renal es sensible a la acción de fármacos, especialmente en el túbulo proximal y distal, que están constituidos por células especializadas con gran actividad metabólica dedicada al transporte de solutos. En esta comunicación se describen diversos fármacos que interfieren con el túbulo-intersticio renal en forma aguda o crónica, se explican los mecanismos de daño renal y las formas de evitarlos en el momento del uso clínico de nefrotóxicos. También se hace referencia a aquellos fármacos cuya eliminación es principalmente por filtración glomerular, por lo que su administración debe ajustarse al cálculo de esta variable funcional para evitar toxicidades en órganos y tejidos, incluido el riñón.

Kidney structure and function, especially at the proximal and distal tubule, are sensitive to the toxic action of different substances that are actively transported at those levels. This Communication describes the most common drugs that damage, in an acute or chronic form, the tubuleinterstitial segment of the renal tissue and describe some ways to prevent nephrotoxicity. Also, the paper refers to a second mechanism of damage due to drug accumulation when administered to patients with some degree of renal dysfunction. To avoid renal toxicity the prescription must be adjusted to a calculated renal clearance obtained previous drug administration.

Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais / Nonsteroidal anti-inflammatory drugs: cardiovascular, cerebrovascular and renal effects

Os anti-inflamatórios não esteroides (AINEs) encontram-se entre os medicamentos mais prescritos em todo o mundo. Essa classe heterogênea de fármacos inclui a aspirina e vários outros agentes inibidores da ciclo-oxigenase (COX), seletivos ou não. Os AINEs não seletivos são os mais antigos, e designados como tradicionais ou convencionais. Os AINEs seletivos para a COX-2 são designados COXIBEs. Nos últimos anos, tem sido questionada a segurança do uso dos AINEs na prática clínica, particularmente dos inibidores seletivos da COX-2. As evidências sobre o aumento do risco cardiovascular com o uso de AINEs são ainda incompletos, pela ausência de ensaios randomizados e controlados com poder para avaliar desfechos cardiovasculares relevantes. Entretanto, os resultados de estudos clínicos prospectivos e de meta-análises indicam que os inibidores seletivos da COX-2 exercem importantes efeitos cardiovasculares adversos, que incluem aumento do risco de infarto do miocárdio, acidente vascular cerebral, insuficiência cardíaca, insuficiência renal e hipertensão arterial. O risco desses efeitos adversos é maior em pacientes com história prévia de doença cardiovascular ou com alto risco para desenvolvê-la. Nesses pacientes, o uso de inibidores da COX-2 deve ser limitado àqueles para os quais não há alternativa apropriada e, mesmo assim, somente em doses baixas e pelo menor tempo necessário. Embora os efeitos adversos mais frequentes tenham sido relacionados à inibição seletiva da COX-2, a ausência de seletividade para essa isoenzima não elimina completamente o risco de eventos cardiovasculares, de modo que todos os fármacos do largo espectro dos AINEs somente devem ser prescritos após consideração do balanço risco/benefício.

The nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most often prescribed drugs in the world. This heterogeneous class of drugs includes aspirin and several other selective or non-selective cyclooxygenase (COX) inhibitors. The non-selective NSAIDs are the oldest ones and are called traditional or conventional NSAIDs. The selective NSAIDs are called COX-2 inhibitors. In recent years, the safety of NSAID use in clinical practice has been questioned, especially that of the selective COX-2 inhibitors. The evidence on the increase in cardiovascular risk with the use of NSAIDs is still scarce, due to the lack of randomized and controlled studies with the capacity of evaluating relevant cardiovascular outcomes. However, the results of prospective clinical trials and meta-analyses indicate that the selective COX-2 inhibitors present important adverse cardiovascular effects, which include increased risk of myocardial infarction, cerebrovascular accident, heart failure, kidney failure and arterial hypertension. The risk of these adverse effects is higher among patients with a previous history of cardiovascular disease or those at high risk to develop it. In these patients, the use of COX-2 inhibitors must be limited to those for which there is no appropriate alternative and, even in these cases, only at low doses and for as little time as possible. Although the most frequent adverse effects have been related to the selective COX-2 inhibition, the absence of selectiveness for this isoenzyme does not completely eliminate the risk of cardiovascular events; therefore, all drugs belonging to the large spectrum of NSAIDs should only be prescribed after consideration of the risk/benefit balance.

Insuficiência renal aguda e rabdomiólise induzida pelo uso de estatina: relato de caso / Acute renal failure and rhabdomyolysis induced by statin: case report

JUSTIFICATIVA E OBJETIVOS: A habilidade das estatinas em reduzir a morbimortalidade dos pacientes com dislipidemia está bem estabelecida. Os efeitos adversos são geralmente leves e temporários. As complicações mais importantes e indesejáveis são a elevação das enzimas hepáticas, miopatia e rabdomiólise, que se caracteriza por necrose muscular, mioglobinúria e insuficiência renal aguda. No geral, as estatinas estão relacionadas a um pequeno risco de miopatia que pode progredir para rabdomiólise fatal ou não fatal. A incidência está relacionada com a dose e o uso concomitante de agentes que compartilham a mesma via metabólica das estatinas. A insuficiência renal aguda é a mais temida complicação da rabdomiólise e a principal causa de óbito. O reconhecimento e tratamento precoce podem prevenir a progressão da rabdomiólise. RELATO DO CASO: Paciente do sexo masculino, 57 anos, sem história prévia de doença renal evolui com insuficiência renal aguda e rabdomiólise, induzida por alta dose de estatina (sinvastatina 80 mg/dia). CONCLUSÃO: Os clínicos devem estar alerta para as interações medicamentosas das estatinas a fim de minimizar o risco de miopatia. Ao prescrever estatinas o médico deve considerar as comorbidades e fatores de risco, incluindo uso de múltiplas medicações, e iniciar estatina com a menor dose possível em idosos. Se houver suspeita deste efeito adverso, o fármaco deve ser suspenso.(AU)

BACKGROUND AND OBJECTIVES: The ability of statins to reduce the risk of cardiovascular morbimortality in patients with dyslipidemia is well established. The adverse effects associated with statins are usually mild and transient. The most noteworthy adverse effects associated with statins are elevations in liver transaminasis, myopathy and rhabdomyolysis, which is characterized by massive muscle necrosis, myoglobinuria and acute renal failure. In general, statins are associated with a very small risk of myopathy (with may progress to fatal or nonfatal rhabdomyolysis). The incidence is dose related and is increased when statins are used in combination with agents that share common metabolic pathways. Acute renal failure is the most serious complication of rhabdomyolysis and the main cause of death. Early recognition and treatment may prevent the progression of rhabdomyolysis. CASE REPORT: A 57 year-old-man, with no history of renal dysfunction presented with acute renal failure and rhabdomyolysis induced by high-dose statin (simvastatin 80 mg/day). CONCLUSION: Clinicians should be alert for drug-drug interactions to minimize the risk of myopathy. The prescribing physician should consider the co-morbid risk factors, including polypharmacy, and initiate statin at a lower dose in the elderly. If rhabdomyolysis is suspected the statin therapy should be withdrawn.(AU)

Efeitos da ciclosporina a sobre a função renal de cães da raça Golden Retriever normais ou afetados pela distrofia muscular / Effect of cyclosporin A on renal functions of normal Golden Retriever dogs or Golden Retriever with muscular dystrophy

A distrofia muscular dos cães Golden Retriever (GRMD), uma miopatia degenerativa causada pela ausência da distrofina, é geneticamente homóloga à distrofia muscular de Duchenne que acomete humanos, portanto, estes cães são considerados modelos experimentais para estudos em terapia celular. Seu sucesso depende da imunossupressão adequada. A ciclosporina A é indicada para tal e a monitorização de suas concentrações sangüíneas e efeitos adversos são essenciais para viabilizar a terapia. Foram estudados cães GRMD e normais da mesma raça, submetidos à terapia com CsA, associada, nos GRMD, ao transplante de células tronco. Foram avaliados os possíveis efeitos do fármaco sobre a função renal, sendo consideradas as manifestações clínicas, urinálise, testes de função glomerular, e concentrações séricas de uréia, creatinina, sódio e potássio. Como resultado houve aumento discreto na uréia sérica de ambos os grupos; cilindrúria e proteinúria e aumento da densidade urinária no grupo dos GRMD. Concluímos que a CsA pode causar lesão aguda de túbulos renais, principalmente em GRMDs; os mesmos também reagem de modo distinto com relação à homeostase de íons e função renal. Entretanto, diagnóstico precoce e tratamento podem prevenir o agravamento das lesões e desenvolvimento de insuficiência renal.

The muscular dystrophy of Golden Retriever is a degenerative miopaty caused by the absence of dystrophy and it is genetically homologue of the Duchenne muscular dystrophy in humans, so, these dogs are considerably experimental models for studies on cellular therapy. Their successful depends of the adequate immunosuppression. Cyclosporin A is indicated for that and the monitoring of blood concentration and adverse effects are essential to viabilise the therapy. It was studied GRMD dogs, and normal dogs from the same breed, submitted for therapy with CsA, associated, on GRMD, of cell transplantation. It was evaluated the possible effects of the drug on renal functions. It has been considerate the clinic manifestations, urinalisis, testis of glomerular function and blood concentrations of urea, cretinine, sodium and potassium. In our results we found a discrete increase of blood urea on booth groups; increased levels of urine's cylinders and protein and also increase of urinary density on GRMD group. CsA therapy could make acute lesions on renal tubules, especially on GRMD. These dogs also have different reactions than normal dogs on relation of ions homeostasis and renal function. However, earlier diagnosis and adequate treatment could prevent the development of renal diseases.

High prevalence of indinavir-associated renal complications in Thai HIV-infected patients.

BACKGROUND: Indinavir (IDV) is the protease inhibitor (PI) used most often in resource-limited countries. The present study aimed to determine the prevalence of IDV-associated renal complications as well as their clinical characteristics. MATERIAL AND METHOD: The authors reviewed all patients participating in cohorts of indinavir-containing regimens at the HIV-NAT research center during the period of indinavir treatment. Patients who had pre-existing renal diseases were excluded. Renal toxicities included presence of urologic symptoms, nephrolithiasis, abnormal urine sediments, crystalluria and loss of renal function. Radiological studies of KUB system were reviewed as well. RESULTS: Two-hundred and four patients treated with IDV were included. Median (IQR) follow up period was 216 (150-312) weeks. One hundred and eighty patients were treated with ritonavir-boosted regimens at some point, and 24 patients were treated only with unboosted regimens. Leukocyturia (51.9%) was the most common finding of IDV-associated renal complications. Thirty-five percent of patients had urologic symptoms such as flank pain or dysuria. Almost half of the patients had significant loss of renal function that was associated with prolonged use of IDV The most common radiological finding was nephrolithiasis. Less common, but of greater clinical importance, are nephrocalcinosis or renal atrophy. CONCLUSION: A high prevalence of IRC was found in Thai HIV-infected patients. As long as no other cost-effective boosted PI regimens are available, strategies to prevent irreversible loss of renal function are warranted.

Protective effect of coenzyme Q10 in simvastatin and gemfibrozil induced rhabdomyolysis in rats.

Administration of simvastatin (80 mg/kg, po. evening dose) and gemfibrozil (600 mg/kg, po twice) for 30 days produced significant decrease in the level of reduced glutathione, superoxide dismutase, catalase and increase in the level of lipid peroxidation and various serum parameters (creatine phosphokinase, lactate dehydrogenase, serum glutamate oxaloacetate transaminase, creatinine, urea and blood urea nitrogen). This suggested involvement of oxidative stress in rhabdomyolysis. Increase in the level of reduced glutathione, superoxide dismutase, catalase and decrease in the level of lipid peroxidation and serum parameters after administration of antioxidant CoQ10 (10 mg/kg.ip) proved the protective effect of CoQ10 in rhabdomyolysis.

Síndrome del ácido transretinoico: Reporte de un caso y revisión de la literatura / All-Trans retinoic acid Syndrome: Case Report and a Review of the Literature

Se describe el caso de una enferma con leucemia aguda promielocítica (LAP) que desarrolló síndrome del ácido transretinoico (SATRA) y se revisa la literatura. El SA TRA se presenta en enfermos con LAP tratados con ácido transretinoico (ATRA). Tiene incidencia de 5% a 27% con mortalidad de hasta 29%. Es secundario al efecto del ATRA sobre la diferenciación de los promielocitos, lo que desencadena respuesta inflamatoria sistémica, daño endotelial con síndrome de fuga capilar y obstrucción de la microcirculación e infiltración tisular. Clínicamente se manifiesta con fiebre, hipotensión, insuficiencia respiratoria, renal y hepática, infiltrados pulmonares, derrame pleural y pericárdico, y edema generalizado. El tratamiento es a base de suspensión del ATRA, medidas de apoyo y esferoides.

We described a patient with acute promyelocytic leukemia (APL) who developed all-trans retinoic acid syndrome (ATRAS) and reviewed the literature. ATRAS presents in patients with APL treated with all-trans retinoic acid (ATRA). It has an incidence from 5%-27% with mortality of 29%. It is secondary to ATRA effect on promyelocyte differentiation, which causes systemic inflammatory response syndrome, endothelium damage with increase in capillary permeability, microcirculation obstruction, and tissue infiltration. ATRAS clinical manifestations are fever, hypotension, respiratory, renal and hepatic insufficiency, lung infiltrates, pleural and pericardic efussion, and generalized edema. Treatment is based on ATRA suspension, support measures, and steroids.