Fisiopatologia e tratamento da síndrome nefrótica: conceitos atuais

Our objective is to review the pathophysiology and treatment of the nephrotic syndrome. This article includes definitions and causes of nephrotic syndrome, and an assessment of the pathophysiology of the nephrotic edema as well as of the causes and treatment of refractory edema. An algorithm for the treatment nephrotic edema is proposed taking into account the complexity of refractory edema. We also address measures aimed at reducing proteinuria, such as the use of angiotensin-converting enzyme inhibitors, hypoprotein diet, and the roles of non-steroidal anti-inflammatory drugs in this context. We also review the complications of nephrotic syndrome such as hyperlipidemia and the hypercoagulability with regards to their pathophysiology and current treatment.Foram revisados aspectos da fisiopatologia e do tratamento sindrômico do estado nefrótico. São citados o conceito e as causas de síndrome nefrótica. Foram revisadas a fisiopatologia do edema, bem como as causas e o tratamento do edema refratário. É apresentado um fluxograma para o manejo clínico do edema nefrótico, considerando a complexidade do edema refratário. Foram abordadas medidas para redução de proteinúria, como o uso de inibidores da enzima de conversão da angiotensina, a dieta hipoproteica e o papel dos antiinflamatórios não esteróides neste contexto. Foram revistas as complicações da síndrome nefrótica, como dislipidemia e hipercoagulabilidade, no que concerne à sua fisiopatologia e tratamento atual

Doença renal ateroembólica: uma causa de insuficiência renal aguda pouco explorada

O ateroembolismo é uma doença multisistêmica que afeta vários órgãos, entre os quais o rim, através da liberação de êmbolos de colesterol de uma placa aterosclerótica erosada, ocasionando obstrução vascular em diversos tecidos. A doença renal ateroembólica (DRAE), histologicamente representada por cristais de colesterol nas arteríolas do rim acompanhados de um infiltrado inflamatório perivascular, é causa de insuficiência renal aguda muitas vezes grave e prolongada, que ocorre semanas ou mesmo meses após o episódio embólico. A DRAE apresesenta prognóstico ruim com elevada mortalidade. Apresentamos neste relato o caso de um paciente com DRAE que se manifestou clinicamente dois meses após a realização de um cateterismo cardíaco seguido de uma angioplastia coronária. A prevalência, manifestações clínicas, histologia renal, tratamento e o prognóstico da DRAE são discutidos.Atheroembolism is a multisytemic disease which affects many organs, including the kidneys, by the release of cholesterol emboli to tissues from an erosed atherosclerotic plaque, causing vascular obstruction in many tissues. The atheroembolic renal disease (AERD) is histologically represented by cholesterol crystals in renal arterioles with an inflammatory infiltrate around the vessels, and causes acute renal failure that may be severe and prolonged, weeks or even months after the embolic episode. The AERD carries a bad prognosis, with a high mortality. We herein report a case of a patient presenting AERD which was manifested two months after he was submitted to a cardiac catheterism and coronary angioplasty. The prevalence, clinical findings, renal histology, treatment and prognosis of AERD are discussed

Tratamento da nefropatia lúpica severa: efeito da ciclofosfamida endovenosa prolongada e intermitente

OBJECTIVE: Intravenous cyclophosphamide is widely used in the treatment of lupus nephritis. In order to analyze long-term outcome in patients with severe lupus nephritis, we studied 54 patients treated with cyclophosphamide at our services between 1989 and 1999. MATERIALS AND METHODS: Our study included 42 patients. According to World Health Organization classification, the initial renal biopsy indicated lupus nephritis class III in 16.7% patients and class IV in 83.3%. The average serum creatinine and proteinuria at the beginning of treatment were, respectively 3.1 ± 2.5 mg/dl and 7.2 ± 5.4 g/24h/1.73m2. Eighty-eight percent of patients had nephrotic range proteinuria and 83.3% had serum creatinine levels higher than 1.2mg/dl. The mean duration of nephritis before treatment was 10 months; however, in 52% of patients it was less than 6 months. Average follow-up time from the beginning of treatment to outcome (end-stage renal disease or death) was 72.2 ± 36.3 months. Patients received immunosuppressive therapy according to the National Institutes of Health protocol and were classified, according to clinical and laboratory response into complete remission, partial remission, or treatment failure. RESULTS: Total or partial remission was achieved in 70% of patients by the end of the first year; 62.5 % of patients were kept in remission up to the third year. The 3, 5, and 10-year actuarial renal survival rates were of 90.2%, 90.2%, and 77.67%, respectively. One patient died and 5 had to start hemodialysis. The adverse effects of immunosuppression were respiratory infection (19.0%), Herpes Zoster (7.1%), temporary (9.5%) and permanent (2.3%) amenorrhea, avascular necrosis of the femoral head (4.7%), and sepsis (2.3%). Neither hemorrhagic cystitis nor neoplasia were observed during follow-up. CONCLUSIONS: We concluded that intravenous cyclophosphamide was effective in the control of acute lupus nephritis and in the maintenance of long-term renal function without serious adverse events. OBJETIVOS: A ciclofosfamida intravenosa é amplamente usada no tratamento da nefrite lúpica. Para analisar os desfechos a longo prazo, estudamos 54 pacientes tratados com ciclofosfamida no período compreendido entre 1989 e 1999. MATERIAIS E MÉTODOS: Quarenta e dois pacientes foram incluídos no estudo. As biópsias renais revelaram, de acordo com a classificação da Organização Mundial de Saúde, nefrite lúpica classe III em 16,7% dos pacientes e classe IV em 83,3%. No início do tratamento, médias de creatinina sérica e proteinúria foram, respectivamente de 3,1 ± 2,5 mg/dl e 7,2 ± 5,4g/24h/1.73m2. Oitenta e oito por cento dos pacientes tinham proteinúria nefrótica, e em 83,3% a creatinina sérica era maior que 1,2 mg/dl. A duração média da nefrite anterior ao tratamento era de 10 meses, porém em 52% dos pacientes a duração era inferior a 6 meses. O seguimento médio desde o início do tratamento até os desfechos avaliados (insuficiência renal crônica terminal ou morte) foi de 72,2 ± 36,3 meses. Os pacientes receberam tratamento imunossupressor de acordo com o protocolo do National Institutes of Health dos Estados Unidos. Os pacientes foram classificados de acordo com a resposta clínico-laboratorial em remissãocompleta, remissão parcial ou falha do tratamento. RESULTADOS: Remissão total ou parcial foi alcançada em 70% dos pacientes no final do primeiro ano, e 62,5 % se mantiveram em remissão no final do terceiro ano. A sobrevida renal atuarial no 3º, 5º e 10º anos foram de 90,2%, 90,2% e 77,67%, respectivamente. Um paciente evoluiu para óbito e cinco necessitaram iniciar hemodiálise. Efeitos adversos do tratamento imunossupressor foram infecção respiratória (19,0%), Herpes Zoster (7,1%), amenorréia transitória (9,5%) e permanente (2,3%), necrose avascular de fêmur (4,7%) e sepse (2,3%). No período de seguimento não foi observada a ocorrência de cistite hemorrágica ou neoplasia. CONCLUSÕES: Concluímos que ciclofosfamida endovenosa foi efetiva no controle da nefrite lúpica aguda e na manutenção da função renal a longo prazo, sem a ocorrência de efeitos adversos sérios

Prognostic molecular markers in early breast cancer

A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D(1 )and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Fisiopatologia e tratamento da síndrome nefrótica: conceitos atuais

Our objective is to review the pathophysiology and treatment of the nephrotic syndrome. This article includes definitions and causes of nephrotic syndrome, and an assessment of the pathophysiology of the nephrotic edema as well as of the causes and treatment of refractory edema. An algorithm for the treatment nephrotic edema is proposed taking into account the complexity of refractory edema. We also address measures aimed at reducing proteinuria, such as the use of angiotensin-converting enzyme inhibitors, hypoprotein diet, and the roles of non-steroidal anti-inflammatory drugs in this context. We also review the complications of nephrotic syndrome such as hyperlipidemia and the hypercoagulability with regards to their pathophysiology and current treatment.Foram revisados aspectos da fisiopatologia e do tratamento sindrômico do estado nefrótico. São citados o conceito e as causas de síndrome nefrótica. Foram revisadas a fisiopatologia do edema, bem como as causas e o tratamento do edema refratário. É apresentado um fluxograma para o manejo clínico do edema nefrótico, considerando a complexidade do edema refratário. Foram abordadas medidas para redução de proteinúria, como o uso de inibidores da enzima de conversão da angiotensina, a dieta hipoproteica e o papel dos antiinflamatórios não esteróides neste contexto. Foram revistas as complicações da síndrome nefrótica, como dislipidemia e hipercoagulabilidade, no que concerne à sua fisiopatologia e tratamento atual

Tratamento da nefropatia lúpica severa: efeito da ciclofosfamida endovenosa prolongada e intermitente

OBJECTIVE: Intravenous cyclophosphamide is widely used in the treatment of lupus nephritis. In order to analyze long-term outcome in patients with severe lupus nephritis, we studied 54 patients treated with cyclophosphamide at our services between 1989 and 1999. MATERIALS AND METHODS: Our study included 42 patients. According to World Health Organization classification, the initial renal biopsy indicated lupus nephritis class III in 16.7% patients and class IV in 83.3%. The average serum creatinine and proteinuria at the beginning of treatment were, respectively 3.1 ± 2.5 mg/dl and 7.2 ± 5.4 g/24h/1.73m2. Eighty-eight percent of patients had nephrotic range proteinuria and 83.3% had serum creatinine levels higher than 1.2mg/dl. The mean duration of nephritis before treatment was 10 months; however, in 52% of patients it was less than 6 months. Average follow-up time from the beginning of treatment to outcome (end-stage renal disease or death) was 72.2 ± 36.3 months. Patients received immunosuppressive therapy according to the National Institutes of Health protocol and were classified, according to clinical and laboratory response into complete remission, partial remission, or treatment failure. RESULTS: Total or partial remission was achieved in 70% of patients by the end of the first year; 62.5 % of patients were kept in remission up to the third year. The 3, 5, and 10-year actuarial renal survival rates were of 90.2%, 90.2%, and 77.67%, respectively. One patient died and 5 had to start hemodialysis. The adverse effects of immunosuppression were respiratory infection (19.0%), Herpes Zoster (7.1%), temporary (9.5%) and permanent (2.3%) amenorrhea, avascular necrosis of the femoral head (4.7%), and sepsis (2.3%). Neither hemorrhagic cystitis nor neoplasia were observed during follow-up. CONCLUSIONS: We concluded that intravenous cyclophosphamide was effective in the control of acute lupus nephritis and in the maintenance of long-term renal function without serious adverse events. OBJETIVOS: A ciclofosfamida intravenosa é amplamente usada no tratamento da nefrite lúpica. Para analisar os desfechos a longo prazo, estudamos 54 pacientes tratados com ciclofosfamida no período compreendido entre 1989 e 1999. MATERIAIS E MÉTODOS: Quarenta e dois pacientes foram incluídos no estudo. As biópsias renais revelaram, de acordo com a classificação da Organização Mundial de Saúde, nefrite lúpica classe III em 16,7% dos pacientes e classe IV em 83,3%. No início do tratamento, médias de creatinina sérica e proteinúria foram, respectivamente de 3,1 ± 2,5 mg/dl e 7,2 ± 5,4g/24h/1.73m2. Oitenta e oito por cento dos pacientes tinham proteinúria nefrótica, e em 83,3% a creatinina sérica era maior que 1,2 mg/dl. A duração média da nefrite anterior ao tratamento era de 10 meses, porém em 52% dos pacientes a duração era inferior a 6 meses. O seguimento médio desde o início do tratamento até os desfechos avaliados (insuficiência renal crônica terminal ou morte) foi de 72,2 ± 36,3 meses. Os pacientes receberam tratamento imunossupressor de acordo com o protocolo do National Institutes of Health dos Estados Unidos. Os pacientes foram classificados de acordo com a resposta clínico-laboratorial em remissãocompleta, remissão parcial ou falha do tratamento. RESULTADOS: Remissão total ou parcial foi alcançada em 70% dos pacientes no final do primeiro ano, e 62,5 % se mantiveram em remissão no final do terceiro ano. A sobrevida renal atuarial no 3º, 5º e 10º anos foram de 90,2%, 90,2% e 77,67%, respectivamente. Um paciente evoluiu para óbito e cinco necessitaram iniciar hemodiálise. Efeitos adversos do tratamento imunossupressor foram infecção respiratória (19,0%), Herpes Zoster (7,1%), amenorréia transitória (9,5%) e permanente (2,3%), necrose avascular de fêmur (4,7%) e sepse (2,3%). No período de seguimento não foi observada a ocorrência de cistite hemorrágica ou neoplasia. CONCLUSÕES: Concluímos que ciclofosfamida endovenosa foi efetiva no controle da nefrite lúpica aguda e na manutenção da função renal a longo prazo, sem a ocorrência de efeitos adversos sérios