RESUMO
PURPOSE: Using urinary indices as a quick bedside test to assist management of oliguria and acute kidney injury (AKI) has long been sought. This study assessed whether urinary potassium excretion is related to simultaneously calculated creatinine clearance (CrCl) and can predict AKI in the critically ill. MATERIALS AND METHODS: In this prospective cohort study, the correlation between 2-h urinary potassium excretion and simultaneously calculated CrCl of 61 critically ill patients was assessed by Pearson's correlation coefficient, and their ability to predict AKI (≥stage 1 KDIGO) in the subsequent 7â¯days was assessed by area under the receiver-operating-characteristic (AUROC) curve. RESULTS: Urinary potassium excretion (median 6.2â¯mmol, range 0.8-24.3) correlated linearly with CrCl (correlation coefficient: 0.58, 95% confidence interval [CI] 0.38-0.72; pâ¯=â¯0.001), and had a moderate ability to predict subsequent AKI (nâ¯=â¯19 [31%]; AUROC 0.747, 95%CI 0.620-0.850; pâ¯=â¯0.001), especially in patients without prior exposure to furosemide within 24-h (correlation coefficient 0.61, 95%CI 0.41-0.76; AUROC 0.789, 95%CI 0.654-0.890; pâ¯=â¯0.001, respectively). CONCLUSIONS: Urinary potassium excretion correlates with CrCl and predicts AKI in the critically ill without recent furosemide exposure. Given 2-h urinary potassium excretion can be measured easily, its potential as a marker of renal function deserves further study.
Assuntos
Injúria Renal Aguda/urina , Creatinina/urina , Unidades de Terapia Intensiva , Potássio/urina , Injúria Renal Aguda/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Biomarcadores/urina , Cloretos/urina , Compostos de Cromo/urina , Estado Terminal , Feminino , Furosemida , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Adulto JovemRESUMO
Multiple Sclerosis is an inflammatory, auto-immune, neurodegenerative disease of the central nervous system. The disease has a prevalence of approx 1:700 with at least 2.5 million cases worldwide. It is the leading, non-trauma cause of physical disability among young and mid- dle-aged adults. Recently developed therapies do reduce disease activity but only modestly, with all of the available agents producing significant side effects that reduce compliance, and/ or serious risk for adverse events. Relaxin has been long-recognized to play a critical role in pregnancy. Recent investigations have revealed that relaxin may be an important regulator of inflammation and immune processes. This is due to the ability of relaxin to promote the pro- duction of glucocorticoid receptors, increase serum levels of the adrenocorticotropic hormone and inhibiting cell-mediated pro-inflammatory activity by stimulation of the peroxisome prolif- erator-activated receptor gamma. This study found serum relaxin levels to be elevated in sub- jects with multiple sclerosis. Production of relaxin is down regulated by a negative feedback loop through its own receptor binding. Decreased receptor binding may contribute to the high- er level of relaxin seen in these patients and may lead to dysregulation of the inflammatory and immune pathways.
RESUMO
Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system (CNS). Many nerve axons are insulated by a myelin sheath and their demyelination not only prevents saltatory electrical signal conduction along the axons but also removes their metabolic support leading to irreversible neurodegeneration, which currently is untreatable. There is much interest in potential therapeutics that promote remyelination and here we explore use of leukaemia inhibitory factor (LIF), a cytokine known to play a key regulatory role in self-tolerant immunity and recently identified as a pro-myelination factor. In this study, we tested a nanoparticle-based strategy for targeted delivery of LIF to oligodendrocyte precursor cells (OPC) to promote their differentiation into mature oligodendrocytes able to repair myelin. Poly(lactic-co-glycolic acid)-based nanoparticles of â¼120 nm diameter were constructed with LIF as cargo (LIF-NP) with surface antibodies against NG-2 chondroitin sulfate proteoglycan, expressed on OPC. In vitro, NG2-targeted LIF-NP bound to OPCs, activated pSTAT-3 signalling and induced OPC differentiation into mature oligodendrocytes. In vivo, using a model of focal CNS demyelination, we show that NG2-targeted LIF-NP increased myelin repair, both at the level of increased number of myelinated axons, and increased thickness of myelin per axon. Potency was high: a single NP dose delivering picomolar quantities of LIF is sufficient to increase remyelination. Impact statement Nanotherapy-based delivery of leukaemia inhibitory factor (LIF) directly to OPCs proved to be highly potent in promoting myelin repair in vivo: this delivery strategy introduces a novel approach to delivering drugs or biologics targeted to myelin repair in diseases such as MS.