Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial)

We performed a double-blind placebo-controlled trial to study whether early treatment with erythropoietin could prevent the development of acute kidney injury in patients in two general intensive care units. As a guide for choosing the patients for treatment we measured urinary levels of two biomarkers, the proximal tubular brush border enzymes γ-glutamyl transpeptidase and alkaline phosphatase. Randomization to either placebo or two doses of erythropoietin was triggered by an increase in the biomarker concentration product to levels above 46.3, with a primary outcome of relative average plasma creatinine increase from baseline over 4 to 7 days. Of 529 patients, 162 were randomized within an average of 3.5 h of a positive sample. There was no difference in the incidence of erythropoietin-specific adverse events or in the primary outcome between the placebo and treatment groups. The triggering biomarker concentration product selected patients with more severe illness and at greater risk of acute kidney injury, dialysis, or death; however, the marker elevations were transient. Early intervention with high-dose erythropoietin was safe but did not alter the outcome. Although these two urine biomarkers facilitated our early intervention, their transient increase compromised effective triaging. Further, our study showed that a composite of these two biomarkers was insufficient for risk stratification in a patient population with a heterogeneous onset of injury.

Creatine pretreatment prevents birth asphyxia–induced injury of the newborn spiny mouse kidney

Background:
Acute kidney injury (AKI) is a major complication for infants following an asphyxic insult at birth. We aimed to determine if kidney structure and function were affected in an animal model of birth asphyxia and if maternal dietary creatine supplementation could provide an energy reserve to the fetal kidney, maintaining cellular respiration during asphyxia and preventing AKI.

Methods:
Pregnant spiny mice were maintained on normal chow or chow supplemented with creatine from day 20 gestation. On day 38 (term ~39 d), pups were delivered by cesarean section (c-section) or subjected to intrauterine asphyxia. Twenty-four hours after insult, kidneys were collected for histological or molecular analysis. Urine and plasma were also collected for biochemical analysis.

Results:
AKI was evident at 24 h after birth asphyxia, with a higher incidence of shrunken glomeruli (P < 0.02), disturbance to tubular arrangement, tubular dilatation, a twofold increase (P < 0.02) in expression of Ngal (early marker of kidney injury), and decreased expression of the podocyte differentiation marker nephrin. Maternal creatine supplementation prevented the glomerular and tubular abnormalities observed in the kidney at 24 h and the increased expression of Ngal.

Conclusion:
Maternal creatine supplementation may prove useful in ameliorating kidney injury associated with birth asphyxia.

Acute farm injury

Using the 'integrative framework', based on the health promoting PRECEDE framework and Haddon's injury prevention strategies, as suggested by Gielen, a theoretical model for general practitioner involvement in the prevention of farm injury was developed. A listing of potential roles in farm injury prevention for general practitioners was produced.

Identification of a by-product of nitric oxide synthase activity in human acute brain injury with in vivo proton magnetic resonance spectroscopy

BACKGROUND AND PURPOSE: Laboratory studies have been used to identify nitric oxide as a notable mediator in neuronal death after acute brain injury. To our knowledge, this has not previously been confirmed with in vivo study in humans. Our purpose was to seek in vivo evidence for the induction of nitric oxide synthase (NOS) in human acute brain injury by using proton MR spectroscopy.

METHODS: In vitro proton MR spectra were obtained in neural extracts from 30 human cadavers, and in vivo spectra were obtained in 20 patients with acute brain injury and in a similar number of control subjects.

RESULTS: We identified a unique peak at 3.15 ppm by using in vivo proton MR spectroscopy in eight of 20 patients with acute brain injury but not in 20 healthy volunteers (P < .002). On the basis of in vitro data, we have tentatively assigned this peak to citrulline, a NOS by-product.

CONCLUSION: To our knowledge, our findings suggest, for the first time, that excitotoxicity may occur in human acute brain injury. Confirmation with the acquisition of spectra in very early acute cerebral injury would provide a rationale for the use of neuroprotective agents in these conditions, as well as a new noninvasive method for quantification.

Improving renal patient care without compromising safety: interactive simulated e-learning

The nephrology educators network [NEN] recognised in 2007 that inequities existed in the access and delivery of evidence based renal education programs particularly to nurses in regional and remote areas. To address this, a web-based approach to learning, through the development of peer reviewed, interactive nephrology e-learning programs was adopted. These programs aligned with the tenets of e-learning instructional design and afforded more effective and consistent clinical support and induction for nurses in the renal specialty. The e-learning programs promote a standardised evidence-based approach to nephrology education and were developed by content experts from across Australia and New Zealand. The design methodology avoided the duplication of resources while also encouraging knowledge transfer between participating health organisations.

This paper will discuss the development and successful implementation of these e-learning programs across renal healthcare units in Australasia. Implemented packages include: Introduction to Buttonhole Cannulation – featuring an interactive ultrasound and cannulation application; Introduction to Haemodialysis; Introduction to Peritoneal Dialysis [PD], featuring simulated PD machines, allowing for the teaching of troubleshooting without compromising patient safety. E-learning programs are further supported through interactive case scenarios that present unfolding real world simulations and enable learners to meet different patients and manage their care while learning about key messages relating to renal health. Modules currently in development include; Acute Kidney Injury; Fluid Assessment, Water Quality and Vascular Access. The implementation of these programs assist the facilitation of positive change in teaching and learning practices in nephrology nursing aimed at improving patient outcomes.

Typical and atypical haemolytic uraemic syndrome: A brief case comparison report for nurses

Background: Haemolytic uraemic syndrome (HUS) is one of the main causes of acute kidney injury in children. It is a multifaceted disease, characterised by microangiopathic haemolytic anaemia and thrombocytopaenia. It can often affect multiple organ systems, including the central nervous and renal systems.

Sodium bicarbonate infusion in patients undergoing orthotopic liver transplantation: a single center randomized controlled pilot trial

BACKGROUND: Liver transplantation-associated acute kidney injury (AKI) carries significant morbidity and mortality. We hypothesized that sodium bicarbonate would reduce the incidence and/or severity of liver transplantation-associated AKI. METHODS: In this double-blinded pilot RCT, adult patients undergoing orthotopic liver transplantation were randomized to an infusion of either 8.4% sodium bicarbonate (0.5 mEq/kg/h for the first hour; 0.15 mEq/kg/h until completion of surgery); (n = 30) or 0.9% sodium chloride (n = 30). Primary outcome: AKI within the first 48 h post-operatively.RESULTS: There were no significant differences between the two treatment groups with regard to baseline characteristics, model for end-stage liver disease and acute physiology and chronic health evaluation (APACHE) II scores, and pre-transplantation renal function. Intra-operative factors were similar for duration of surgery, blood product requirements, crystalloid and colloid volumes infused and requirements for vasoactive therapy. Eleven patients (37%) in the bicarbonate group and 10 patients (33%) in the sodium chloride group developed a post-operative AKI (p = 0.79). Bicarbonate infusion attenuated the degree of immediate post-operative metabolic acidosis; however, this effect dissipated by 48 h. There were no significant differences in ventilation hours, ICU or hospital length of stay, or mortality. CONCLUSIONS: The intra-operative infusion of sodium bicarbonate did not decrease the incidence of AKI in patients following orthotopic liver transplantation.

Nephrologists' management of patient medications in kidney transplantation: results of an online survey

Rationale, aims and objectives: Medication adherence is essential in kidney transplant recipients to reduce the risk of rejection and subsequent allograft loss. The aim of this study was to delineate what 'usual care' entails, in relation to medication management, for adult kidney transplant recipients. Methods: An online survey was developed to explore how nephrologists promote and assess medication adherence, the management of prescriptions, the frequency of clinic appointments and the frequency of clinical screening tests. Nephrologists from all acute kidney transplant units in Victoria, Australia, were invited to participate. Data were collected between May and June 2014. Results: Of 60 nephrologists invited to participate, 22 completed the survey (response rate of 36.6%). Respondents had a mean age of 49.1±10.1 years, with a mean of 20.1±9.9 years working in nephrology and 14 were men. Descriptive analysis of responses showed that nephrologists performed frequent screening for kidney graft dysfunction that may indicate medication non-adherence, maintained regular transplant clinic visits with patients and emphasized the importance of medication education. However, time constraints during consultations impacted on extensive patient education and the long-term medication follow-up support was often delivered by the renal transplant nurse coordinator or pharmacist. Conclusions: This study highlighted that nephrologists took an active approach in the medication management of kidney transplant recipients, which may assist with facilitating long-term graft survival. Ultimately, promoting medication adherence needs to be patient centred, involving an interdisciplinary team of nephrologists, pharmacists and renal transplant nurse coordinators, working together with the patient to establish optimal adherence.

Inhibition of reactive oxygen species production ameliorates inflammation induced by influenza A viruses via upregulation of SOCS1 and SOCS3.

Highly pathogenic avian influenza virus infection is associated with severe mortality in both humans and poultry. The mechanisms of disease pathogenesis and immunity are poorly understood although recent evidence suggests that cytokine/chemokine dysregulation contributes to disease severity following H5N1 infection. Influenza A virus infection causes a rapid influx of inflammatory cells, resulting in increased reactive oxygen species production, cytokine expression, and acute lung injury. Proinflammatory stimuli are known to induce intracellular reactive oxygen species by activating NADPH oxidase activity. We therefore hypothesized that inhibition of this activity would restore host cytokine homeostasis following avian influenza virus infection. A panel of airway epithelial and immune cells from mammalian and avian species were infected with A/Puerto Rico/8/1934 H1N1 virus, low-pathogenicity avian influenza H5N3 virus (A/duck/Victoria/0305-2/2012), highly pathogenic avian influenza H5N1 virus (A/chicken/Vietnam/0008/2004), or low-pathogenicity avian influenza H7N9 virus (A/Anhui/1/2013). Quantitative real-time reverse transcriptase PCR showed that H5N1 and H7N9 viruses significantly stimulated cytokine (interleukin-6, beta interferon, CXCL10, and CCL5) production. Among the influenza-induced cytokines, CCL5 was identified as a potential marker for overactive immunity. Apocynin, a Nox2 inhibitor, inhibited influenza-induced cytokines and reactive oxygen species production, although viral replication was not significantly altered in vitro. Interestingly, apocynin treatment significantly increased influenza virus-induced mRNA and protein expression of SOCS1 and SOCS3, enhancing negative regulation of cytokine signaling. These findings suggest that apocynin or its derivatives (targeting host responses) could be used in combination with antiviral strategies (targeting viruses) as therapeutic agents to ameliorate disease severity in susceptible species.

Maternal creatine : does it reach the fetus and improve survival after an acute hypoxic episode in the spiny mouse (Acomys cahirinus)?

Objective
We hypothesized that elevating creatine in the maternal diet would reach fetal and placental tissues and improve fetal survival after acute hypoxia at birth.
Study Design
Pregnant spiny mice were fed a control or 5% creatine-supplemented diet from day 20 of gestation (term, approximately 39 days). On days 37-38, intrauterine hypoxia was induced by placement of the isolated uterus in a saline solution bath for 7.5-8 minutes, after which fetuses were expelled from the uterus and resuscitation was attempted by manual palpation of the chest. Total creatine content (creatine + phosphocreatine) of placental, fetal, and maternal organs was measured.
Results
The maternal creatine diet significantly increased total creatine content in the placenta, fetal brain, heart, liver, and kidney and increased the capacity of offspring to survive birth hypoxia. Maternal creatine improved postnatal growth after birth hypoxia.
Conclusion
This study provides evidence that creatine has potential as a prophylactic therapy for pregnancies that are classified as high risk for fetal hypoxia.

An evidence-based practice approach to improving nursing care of acute stroke in an Australian emergency department

Aims. The aim of this study was to improve the emergency nursing care of acute stroke by enhancing the use of evidence regarding prevention of early complications.
Background. Preventing complications in the first 24–48 hours decreases stroke-related mortality. Many patients spend considerable part of the first 24 hours following stroke in the Emergency Department therefore emergency nurses play a key role in patient outcomes following stroke.
Design. A pre-test/post-test design was used and the study intervention was a guideline for Emergency Department nursing management of acute stroke.
Methods. The following outcomes were measured before and after guideline implementation: triage category, waiting time, Emergency Department length of stay, time to specialist assessment, assessment and monitoring of vital signs, temperature and blood glucose and venous-thromboembolism and pressure injury risk assessment and interventions.
Results. There was significant improvement in triage decisions (21Æ4% increase in triage category 2, p = 0Æ009; 15Æ6% decrease in triage category 4, p = 0Æ048). Frequency of assessments of respiratory rate (p = 0Æ009), heart rate (p = 0Æ022), blood pressure (p = 0Æ032) and oxygen saturation (p = 0Æ001) increased. In terms of risk management, documentation of pressure area
interventions increased by 28Æ8% (p = 0Æ006), documentation of nil orally status increased by 13Æ8% (ns), swallow assessment prior to oral intake increased by 41Æ3% (p = 0Æ003), speech pathology assessment in Emergency Department increased by 6Æ1% (ns) and there was 93Æ5 minute decrease in time to speech pathology assessment for admitted patients (ns).
Relevance to clinical practice. An evidence-based guideline can improve emergency nursing care of acute stroke and optimise patient outcomes following stroke. As the continuum of stroke care begins in the Emergency Department, detailed recommendations for evidence-based emergency nursing care should be included in all multidisciplinary guidelines for the management of acute stroke.