Avaliação da função tubular renal de pacientes sobreviventes de insuficiência renal aguda severa submetidos à diálise

Introdução: Em torno de 30 a 50% dos pacientes críticos desenvolvem insuficiência renal aguda (IRA), sendo que sua progressão leva à necessidade de terapia renal substitutiva (TRS). Dentre os sobreviventes, em torno de 15 a 23% possuem a necessidade de diálise após alta. A ocorrência da insuficiência renal aguda tem sido associada à futura progressão para doença renal crônica. É possível que marcadores tubulares estejam alterados após a recuperação da IRA, antecipando o desenvolvimento de doença renal crônica. Objetivos: Comparar a β2 Microglobulina, as enzimas urinárias N-acetil- β-D-glucosaminidase, lactato desidrogenase e fosfatase alcalina, as frações de excreção de magnésio, fósforo, potássio e ácido úrico e o gradiente transtubular de potássio, bem como a presença de microalbuminúria e proteinúria entre pacientes normais sem qualquer história prévia de dano ou qualquer tipo de disfunção renal, com pacientes sobreviventes de IRA severa com necessidade de hemodiálise que recuperaram função renal de forma a avaliar se existem diferenças entre os 2 grupos. Métodos: Foram incluídos pacientes que apresentaram insuficiência renal aguda com necessidade de hemodiálise internados no centro de terapia intensiva (CTI) do Hospital de Clínicas de Porto Alegre e que receberam alta nos períodos de 2007 a 2010, sem apresentar as seguintes co-morbidades: insuficiência renal crônica, hepatopatia crônica, pacientes HIV positivo, transplantados, doença vascular severa, diabetes com complicações crônicas e rim único funcionante e que apresentavam função renal normal definida por taxa de filtração glomerular > 60 mL/min/1.73m2 calculada pela equação CKD-EPI. Os mesmos foram comparados com voluntários sadios pareados por sexo e idade (+/- 4 anos). Para avaliação das frações de excreção e do gradiente transtubular de potássio foram feitas análises excluindo o uso de medicamentos diuréticos, inibidores da ECA e bloqueadores dos receptores de angiotensina. Resultados: A fração de excreção de magnésio encontrou-se aumentada no grupo com IRA prévia seguida por um menor gradiente transtubular de potássio bem como lactato desidrogenase elevada. O grupo com IRA prévia apresentou proteinúria e microalbuminúria e embora sem significância estatística (P=0,052) uma maior fração de excreção de fósforo. Conclusão: Mesmo com taxa de filtração glomerular normal comparável, os sujeitos do grupo com ira prévia apresentaram sugestivas alterações em nível tubular refletidas por maior fração de excreção de magnésio, elevada lactato desidrogenase e um menor gradiente transtubular de potássio, microalbuminúria e proteinúria que refletem um possível dano renal. Estes achados levam à hipótese de que sujeitos com prévia IRA severa com necessidade de terapia de renal substitutiva, apresentam uma possível sequela relativa à IRA prévia ou uma predisposição para insuficiência renal crônica.Background: About 30 to 50% of the critically ill patients develop acute renal failure (ARF) and the progression leads to the need of renal replacement therapy. Between the survivors 15 to 23% has the need of dialysis after discharge. The severity of the ARF is a robust predictor for the development of a future chronic kidney disease. The occurrence of acute renal failure has been associated with future progression of chronic kidney disease. Objective: Compare β2-microglobulin, the urinary enzymes N-acetyl-β- D-glucosaminidase, lactate dehydrogenase, alkaline phosphatase fractional excretion of magnesium, phosphorous, potassium and uric acid transtubular potassium gradient, including the presence of microalbuminuria and proteinuria between subjects with normal renal function without any previous history of acute renal injury or any kind of renal dysfunction with survivors of severe ARF with the needed of hemodialysis that recovered renal function in order to evaluate if there are differences between the 2 groups. Methods: It was enrolled patients that presented acute renal failure with the need of hemodialysis hospitalized on intensive care unit (ICU) and discharged on the period of 2007 to 2010 at Hospital de Clínicas de Porto Alegre, without the following co-morbidities chronic renal failure, chronic hepatopathy, positive HIV, transplants, severe vascular disease, diabetes with chronic complications and single functioning kidney that presented normal renal function defined as glomerular filtration rate (GFR) > 60 mL/min/1.73m2 calculated by CKD EPI formula The subjects were compared with healthy volunteers and paired by sex and age (+/- 4 years). To evaluate fractional excretions and transtubular potassium gradient, analyses were made excluding subjects that were taken diuretic medication, ACE inhibitors and angiotensin block receptors. Results: The fractional excretion of magnesium was finding increased on the previous ARF group followed by a lower transtubular potassium gradient and elevated lactate dehydrogenase. The previous ARF group showed proteinuria and microalbuminuria and although without statistical significance (p=0.052) an elevated phosphorous excretion. Conclusion: Although normal glomerular filtration rate, the subjects with previous ARF, showed suggested tubular alterations reflected by a higher fractional excretion of magnesium, elevated lactate dehydrogenase and a lower transtubular potassium gradient, microalbuminuria and proteinuria that reflects a possible renal damage. Those findings lead to the hypothesis that subjects with previous severe ARF with the need of renal replacement therapy present a possible sequel related to previous ARF or a predisposition to chronic kidney disease

A double-blind, randomised, crossover trial of two botulinum toxin type A in patients with spasticity

Background: Botulinum toxin type A (btxA) is one of the main treatment choices for patients with spasticity. ProsigneH a new released botulinum toxin serotype A may have the same effectiveness as BotoxH in focal dystonia. However, there are no randomized clinical trials comparing these formulations in spasticity treatment. The aim of our study was to compare the efficacy and safety of ProsigneH with BotoxH in the treatment of spasticity. Methodology/Principal Findings: We performed a double-blind, randomized, crossover study consisting of 57 patients with clinically meaningful spasticity. The patients were assessed at baseline, 4 and 12 weeks after ProsigneH or BotoxH administration. The main outcomes were changes in the patients’ Modified Ashworth Scale (MAS), Functional Independence Measure (FIM) and Pediatric Evaluation of Disability Inventory (PEDI) scores and adverse effects related to the botulinum toxin. Both of the toxins were significantly effective in relieving the level of spasticity in adults and children. There were no significant differences found between the ProsigneH and BotoxH treatments regarding their MAS, FIM and PEDI scores. Likewise, the incidence of adverse effects was similar between the two groups. Conclusion: Our results suggest that ProsigneH and BotoxH are both efficient and comparable with respect to their efficacy and safety for the three month treatment of spasticity

A double-blind, randomised, crossover trial of two botulinum toxin type A in patients with spasticity

Background: Botulinum toxin type A (btxA) is one of the main treatment choices for patients with spasticity. ProsigneH a new released botulinum toxin serotype A may have the same effectiveness as BotoxH in focal dystonia. However, there are no randomized clinical trials comparing these formulations in spasticity treatment. The aim of our study was to compare the efficacy and safety of ProsigneH with BotoxH in the treatment of spasticity. Methodology/Principal Findings: We performed a double-blind, randomized, crossover study consisting of 57 patients with clinically meaningful spasticity. The patients were assessed at baseline, 4 and 12 weeks after ProsigneH or BotoxH administration. The main outcomes were changes in the patients’ Modified Ashworth Scale (MAS), Functional Independence Measure (FIM) and Pediatric Evaluation of Disability Inventory (PEDI) scores and adverse effects related to the botulinum toxin. Both of the toxins were significantly effective in relieving the level of spasticity in adults and children. There were no significant differences found between the ProsigneH and BotoxH treatments regarding their MAS, FIM and PEDI scores. Likewise, the incidence of adverse effects was similar between the two groups. Conclusion: Our results suggest that ProsigneH and BotoxH are both efficient and comparable with respect to their efficacy and safety for the three month treatment of spasticity

Randomized double-blind clinical trial of a new human epoetin versus a commercially available formula for anemia control in patients on hemodialysis

OBJECTIVES: Anemia is a common complication among chronic kidney disease patients on hemodialysis, occurring mostly due to erythropoietin deficiency. This randomized noninferiority trial sought to compare the efficacy and safety of a new epoetin formulation developed by Bio-Manguinhos, a biologics manufacturer affiliated with the Brazilian government, with those of a commercially available product currently used in Brazil (a biosimilar epoetin formulation). METHODS: The sample size needed to enable demonstration of noninferiority with a statistical power of 85% for a between-group difference in hemoglobin levels of no more than 1.5 g/dL was calculated. In total, 74 patients were randomly assigned to receive the epoetin formulation from Bio-Manguinhos (n = 36) or the biosimilar epoetin formulation (n = 38) in a double-blind fashion. The inclusion criteria were current epoetin therapy and stable hemoglobin levels for at least 3 months prior to the study. The primary and secondary outcomes were mean monthly hemoglobin levels and safety, respectively. The dose was calculated according to international criteria and adjusted monthly in both groups according to hemoglobin levels and at the assistant physicians’ discretion. Iron storage was estimated at baseline and once monthly. Clinicaltrials.gov: NCT01184495. RESULTS: The study was conducted for 6 months after randomization. The mean baseline hemoglobin levels were 10.9¡1.2 and 10.96¡1.2 g/dL (p = 0.89) in the Bio-Manguinhos epoetin and biosimilar epoetin groups, respectively. During the study period, there was no significant change in hemoglobin levels in either group (p = 0.055, ANOVA). The epoetin from Bio-Manguinhos was slightly superior in the last 3 months of follow-up. The adverse event profiles of the two formulations were also similar. CONCLUSIONS: The epoetin formulations tested in this study are equivalent in efficacy and safety

Muscles and btxA doses.

*<p>Units btxA.</p