Necrose tubular aguda comprovada por biopsia em paciente com dengue e rabdomiolise

Resultados de histologia renal são muito escassos em pacientes com rabdomiólise e injúria renal aguda (IRA) associada a dengue. Descrevemos caso de dengue complicado por rabdomiólise e IRA no qual a biópsia renal mostrou necrose tubular aguda (NTA) e deposição renal de mioglobina. Paciente de 28 anos que apresentou dengue complicado por IRA grave e rabdomiólise é descrito. Ele necessitou de diálise por três semanas. A biópsia renal mostrou NTA, com imunohistoquímica fortemente positiva para mioglobina nos túbulos renais. O paciente recebeu alta com recuperação da função renal. Em conclusão, descrevemos caso de dengue complicado por IRA e rabdomiólise, em que a biópsia renal mostrou NTA e deposição de mioglobina. Sugerimos que creatinofosfoquinase deve ser monitorizada em pacientes com dengue para permitir o diagnóstico precoce de rabdomiólise e a instituição de medidas protetoras para o rim.Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI). We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN) and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF) complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures

Modificação do fenótipo linfocitário e aumento da sobrevida do enxerto de pele após a terapia com FTY720 + FK506

The development of new drugs to be associated with calcineurin inhibitors and promote additional immunosuppression with fewer side effects is the goal in transplantation. FTY720 is a new synthetic compound which presents immunomodulatory properties which are not fully understood. It has been reported that the main mechanism of action of FTY720 is to reduce the peripheral lymphocyte count by redirecting these cells toward secondary lymphoid organs. Skin allograft transplantation in a fully mismatched strain combination was used to investigate the potential of FTY720 alone or in combination with a calcineurin inhibitor - FK506 - in preventing rejection. The number and phenotype of immune system cells was also evaluated. FTY720 alone or in combination with FK506 provided significant skin allograft survival. FTY720+FK506 therapy was associated with decreases of total lymphocyte numbers in spleen and blood, and increases in apoptosis levels in splenocytes. In FTY720 isolated treatment, a significant decrease in the CD4 expression and significantly lower expressions of MHC II and ICAM-1 molecules were observed in spleen lymphocytes. Despite of allograft survival being the same in both FTY720 and FTY720+FK506 treated groups, the association of drugs was associated with the absence of macroscopic skin necrosis for a longer period than the other treatments (FTY720, FK506) and histology showed less cell infiltration. Our results suggest that a decrease of effector T cells due to elevated levels of apoptosis and impairment in the appearance of antigens were events associated with FTY720+FK506 administration.O objetivo na área dos transplantes é o desenvolvimento de novas drogas que possam ser associadas a inibidores da calcineurina para evitar o processo de rejeição e causar menos efeitos colaterais. FTY720 é um novo composto sintético que apresenta propriedades imunomoduladoras não completamente elucidadas. Foi relatado que o principal mecanismo de ação do FTY720 é a redução do número de linfócitos periféricos através do redirecionamento dessas células para órgãos linfóides secundários. O alotransplante de pele entre linhagens de camundongos completamente incompatíveis quanto ao MHC foi usado para investigar o potencial de FTY720 isolado ou em combinação com um inibidor da calcineurina - FK506 - na prevenção da rejeição. Também foram avaliados o número e fenótipo das células do sistema imune. A administração de FTY720 como monoterapia ou FTY720+FK506 associou-se a uma diminuição do número total de linfócitos no baço e no sangue e aumento dos níveis de apoptose nos esplenócitos. No grupo tratado somente com FTY720, foi observada uma diminuição mais importante da expressão de CD4 e expressão significativamente menor de moléculas de MHC II e ICAM-1. Apesar de a sobrevida do aloenxerto ter sido igual para os grupos tratados com FTY720 ou FTY720 +FK506, a associação das drogas promoveu ausência de necrose macroscópica da pele por um período maior do que os outros tratamentos (FTY720, FK506) e os achados histológicos mostraram menor infiltrado celular. Nossos resultados sugerem que uma diminuição do número de células T efetoras devido a elevados níveis de apoptose e o prejuízo da apresentação de antígenos foram os eventos associados à administração de FTY720+FK506.Faculdade de Medicina de São José do Rio PretoUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Patients with ischaemic, mixed and nephrotoxic acute tubular necrosis in the intensive care unit – a homogeneous population?

INTRODUCTION: Acute tubular necrosis (ATN) is usually studied as a single entity, without distinguishing between ischaemic, nephrotoxic and mixed aetiologies. In the present study we evaluated the characteristics and outcomes of patients with ATN by aetiological group. METHOD: We conducted a retrospective comparison of clinical features, mortality rates and risk factors for mortality for the three types of ATN in patients admitted to the general intensive care unit of a university hospital between 1997 and 2000. RESULTS: Of 593 patients with acute renal failure, 524 (88%) were classified as having ATN. Their mean age was 58 years, 68% were male and 52% were surgical patients. The overall mortality rate was 62%. A total of 265 patients (51%) had ischaemic ATN, 201 (38%) had mixed ATN, and 58 (11%) had nephrotoxic ATN. There were no differences among groups in terms of age, sex, APACHE II score and reason for ICU admission. Multiple organ failure was more frequent among patients with ischaemic (46%) and mixed ATN (55%) than in those with nephrotoxic ATN (7%; P < 0.0001). The complications of acute renal failure (such as, gastrointestinal bleeding, acidosis, oliguria and hypervolaemia) were more prevalent in ischaemic and mixed ATN patients. Mortality was higher for ischaemic (66%; P = 0.001) and mixed ATN (63%; P = 0.0001) than for nephrotoxic ATN (38%). When ischaemic ATN patients, mixed ATN patients and all patients combined were analyzed by multivariate logistic regression, the independent factors for mortality identified were different except for oliguria, which was the only variable universally associated with death (odds ratio [OR] 3.0, 95% confidence interval [CI] 1.64–5.49 [P = 0.0003] for ischaemic ATN; OR 1.96, 95% CI 1.04–3.68 [P = 0.036] for mixed ATN; and OR 2.53, 95% CI 1.60–3.76 [P < 0.001] for all patients combined]). CONCLUSION: The frequency of isolated nephrotoxic ATN was low, with ischaemic and mixed ATN accounting for almost 90% of cases. The three forms of ATN exhibited different clinical characteristics. Mortality was strikingly higher in ischaemic and mixed ATN than in nephrotoxic ATN. Although the type of ATN was not an independent predictor of death, the independent factors related to mortality were different for ischaemic, mixed and all patients combined. These data indicate that the three types of ATN represent different patient populations, which should be taken into consideration in future studies

Extracorporeal Treatment in Phenytoin Poisoning: Systematic Review and Recommendations from the EXTRIP Workgroup

The Extracorporeal Treatments in Poisoning (EXTRIP) Workgroup conducted a systematic literature review using a standardized process to develop evidence-based recommendations on the use of extracorporeal treatment (ECTR) in patients with phenytoin poisoning. The authors reviewed all articles, extracted data, summarized findings, and proposed structured voting statements following a predetermined format. A 2-round modified Delphi method was used to reach a consensus on voting statements, and the RAND/UCLA Appropriateness Method was used to quantify disagreement. 51 articles met the inclusion criteria. Only case reports, case series, and pharmacokinetic studies were identified, yielding a very low quality of evidence. Clinical data from 31 patients and toxicokinetic grading from 46 patients were abstracted. The workgroup concluded that phenytoin is moderately dialyzable (level of evidence = C) despite its high protein binding and made the following recommendations. ECTR would be reasonable in select cases of severe phenytoin poisoning (neutral recommendation, 3D). ECTR is suggested if prolonged coma is present or expected (graded 2D) and it would be reasonable if prolonged incapacitating ataxia is present or expected (graded 3D). If ECTR is used, it should be discontinued when clinical improvement is apparent (graded 1D). The preferred ECTR modality in phenytoin poisoning is intermittent hemodialysis (graded 1D), but hemoperfusion is an acceptable alternative if hemodialysis is not available (graded 1D). In summary, phenytoin appears to be amenable to extracorporeal removal. However, because of the low incidence of irreversible tissue injury or death related to phenytoin poisoning and the relatively limited effect of ECTR on phenytoin removal, the workgroup proposed the use of ECTR only in very select patients with severe phenytoin poisoning

C-Reactive protein and risk of ESRD: results from the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT)

Background: To better understand a potential association of elevated C-reactive protein (CRP) level with progression of chronic kidney disease (CKD), we examined the relationship of CRP level with the development of end-stage renal disease (ESRD) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Study Design Post hoc analysis of a randomized controlled trial. Setting &#38; Participants: 4,038 patients with type 2 diabetes, CKD, and anemia in TREAT. Predictor: Baseline serum CRP concentrations. Outcomes: The primary outcome was development of ESRD; secondary outcomes included doubling of serum creatinine level, a composite of ESRD/serum creatinine doubling, and a composite of death or ESRD. Measurements: We fit unadjusted and adjusted Cox regression models to test the association of baseline CRP level with time to the development of the outcomes of interest. Results: Mean age of participants was 67 years, 43% were men, and 64% were white. Approximately half (48%) the patients had CRP levels &gt; 3.0 mg/L; 668 patients developed ESRD, and 1,270 developed the composite outcome of death or ESRD. Compared with patients with baseline CRP levels ≤ 3.0 mg/L, those with moderately/markedly elevated CRP levels (≥6.9 mg/L; 24% of patients) had a higher adjusted risk for ESRD (HR, 1.32; 95% CI, 1.07-1.63) and the composite outcome of death or ESRD (HR, 1.41; 95% CI, 1.21-1.64). Although nonsignificant, similar trends were noted in competing-risk models. Limitations: Results may not be generalizable to nondiabetic CKD or diabetic CKD in the absence of anemia. Conclusions: Elevated baseline CRP levels are common in type 2 diabetic patients with anemia and CKD and are associated with the future development of ESRD and the composite of death or ESRD

Auditoria interna - o contributo do controlo interno na gestão de risco das organizações

Esta versão contém as correcções às críticas e sugestões dos elementos do júriAs empresas para atingirem a estratégia delineada devem estabelecer um modelo de governance que vise efectuar a gestão do risco, conduzindo á implementação de processos e controlos, para reduzir as ameaças e o risco de incerteza subjacentes às principais actividades ou negócios desenvolvidos. A gestão do risco passa pela análise detalhada dos riscos subjacentes ao negócio. Parte da gestão do risco é realizada pela implementação de um sistema de controlo interno, conducente a mitigar os riscos negativos e a potenciar os riscos positivos para a empresa. O controlo interno é fundamental na gestão do risco, pois trata-se do conjunto de mecanismos e práticas utilizadas para evitar ou detectar actividade não autorizada, com o intuito da realização dos objectivos estratégicos da empresa. Neste sentido, o objectivo deste trabalho passou por evidenciar a importância do processo de gestão do risco no delinear da estratégia de negócio e na condução dos trabalhos para a concretização dos objectivos da empresa, e demonstrar a importância do sistema de controlo interno neste processo e como parte fundamental na mitigação do risco. Inicialmente realizou-se uma pesquisa literária para aprofundar os principais conceitos sobre controlo interno e gestão do risco. Seguidamente, procedeu-se à elaboração de um questionário destinado a profissionais de Auditoria e a outros relacionados com a área em análise, de modo a encontrar consensos entre opiniões. Os resultados obtidos conduziram-nos á validação do modelo de análise, proposto no capítulo metodologia de investigação deste trabalho.Companies to achieve the strategy outlined, must establish a governance model that aims to manage risk, leading to the implementation of processes and controls, to reduce the threats and the risk of uncertainty underlying the main activities or businesses developed. Risk management involves a detailed analysis of the risks underlying the business. Part of risk management is carried out by implementing an internal control system, leading to mitigating negative risks and enhancing positive risks for the company. Internal control is fundamental in risk management, as it is the set of mechanisms and practices used to prevent or detect unauthorized activity, with a view to achieving the company's strategic objectives. In this sense, the objective of this work was to highlight the importance of the risk management process in outlining the business strategy and in conducting the work to achieve the company's objectives, and to demonstrate the importance of the internal control system in this process and how fundamental part in risk mitigation. Initially, a literary research was carried out to deepen the main concepts on internal control and risk management. Then, a questionnaire was created for Audit professionals and other parts related to the area under analysis, in order to find consensus between opinions. The results obtained led us to validate the analysis model proposed, in the research methodology chapter of this work

Stroke in patients with type 2 diabetes mellitus, chronic kidney disease, and anemia treated with darbepoetin alfa: The trial to reduce cardiovascular events with aranesp therapy (TREAT) experience

More strokes were observed in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) among patients assigned to darbepoetin alfa. We sought to identify baseline characteristics and postrandomization factors that might explain this association

Annexin A1 protein attenuates cyclosporine-induced renal hemodynamics changes and macrophage infiltration in rats

Cyclosporine (CsA) remains an important immunosuppressant for transplantation and for treatment of autoimmune diseases. The most troublesome side effect of CsA is renal injury. Acute CsA-induced nephrotoxicity is characterized by reduced renal blood flow (RBF) and glomerular filtration rate (GFR) due to afferent arteriole vasoconstriction. Annexin A1 (ANXA1) is a potent anti-inflammatory protein with protective effect in renal ischemia/reperfusion injury. Here we study the effects of ANXA1 treatment in an experimental model of acute CsA nephrotoxicity. Salt-depleted rats were randomized to treatment with VH (vehicles 1 mL/kg body weight/day), ANXA1 (Ac2-26 peptide 1 mg/kg body weight/day intraperitoneally), CsA (20 mg/kg body weight/day subcutaneously) and CsA + ANXA1 (combination) for seven days. We compared renal function and hemodynamics, renal histopathology, renal tissue macrophage infiltration and renal ANXA1 expression between the four groups. CsA significantly impaired GFR and RBF, caused tubular dilation and macrophage infiltration and increased ANXA1 renal tissue expression. Treatment with ANXA1 attenuated CSA-induced hemodynamic changes, tubular injury and macrophage infiltration. ANXA1 treatment attenuated renal hemodynamic injury and inflammation in an acute CsA nephrotoxicity model.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP [2008/01,048-9]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNPq [306,074/2007-9, 307,371/2006-9

Change in hemoglobin trajectory and darbepoetin dose approaching end-stage renal disease: data from the trial to reduce cardiovascular events with aranesp therapy trial

Background: The pathogenesis of chronic kidney disease associated anemia is multifactorial and includes decreased production of erythropoietin (EPO), iron deficiency, inflammation, and EPO resistance. To better understand the trajectory of these parameters, we described temporal trends in hemoglobin (Hb), ferritin, transferrin saturation, C-reactive protein (CRP), and darbepoetin dosing in the Trial to Reduce cardiovascular Events with Aranesp Therapy (TREAT). Methods: We performed a post hoc analysis of 4,038 participants in TREAT. Mixed effects linear regression models were used to determine the trajectory of parameters of interest prior to end-stage renal disease (ESRD). Likelihood ratio tests were used to determine the overall differences in biomarker values and differences in trajectories between those who did and did not develop ESRD. Results: Hb declined precipitously in the year prior to the development of ESRD (irrespective of treatment assignment), and was on average 1.15 g/dL (95% CI –1.26 to –1.04) lower in those who developed ESRD versus those who did not, at the time of ESRD/end of follow-up. Simultaneously, the mean darbepoetin dose and CRP concentration increased, while serum ferritin and transferrin saturations were &gt;140 μg/L and 20%, respectively. Conclusions: Our analyses provide descriptive insights regarding the temporal changes of Hb, darbepoetin dose, and related parameters as ESRD approaches in participants of TREAT. Hb declined as much as 1–2 years prior to the development of ESRD, without biochemical evidence of iron deficiency. The most precipitous decline occurred in the months immediately prior to ESRD, despite administration of escalating doses of darbepoetin and in parallel with an increase in CRP