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Iodinated radiographic contrast media has been associated with an acute deterioration in renal function, termed contrast induced nephropathy (CIN). This review aims to establish the ...efficacy of prophylaxis interventions used in adult patients prior to intravenous exposure to iodinated contrast to reduce the risk of CIN.
An electronic search for published peer-reviewed articles was performed, supplemented with manual review of references from previous systematic reviews and the National Institute for Health and Care Excellence guidelines. Risk of bias was assessed using the Cochrane Collaboration’s tool for assessing risk of bias. Random-effect meta-analyses were used to assess CIN incidence, need for kidney replacement therapy (KRT), mortality, fluid overload and persistent kidney dysfunction.
22 studies assessing a range of interventions were included in the qualitative analysis. The incidence of CIN was reduced by the use of N-acetylcysteine compared to a control group of saline (risk difference = -0.07, 95% CI −0.13 to −0.01) but not by sodium bicarbonate compared to control group of saline (risk difference = -0.02, 95% CI −0.04 to 0.01). Published studies give no indication that prophylactic interventions have significant impact on the need for KRT, mortality or persistent renal impairment.
Evidence for prophylaxis against CIN in patients receiving intravenous iodinated contrast is limited. There was an association with the use of NAC with reduced incidence of CIN following intravenous contrast but there was no impact on other clinical outcomes assessed. The clinical significance of these findings remains unclear and further research focusing on these clinical outcomes is required.
Abstract
There is a growing body of evidence for the role of deprivation in a broad spectrum of diseases including renal disease. Deprivation has been demonstrated to be associated with poorer ...outcomes across a range of renal diseases including acute kidney injury (AKI), chronic kidney disease and transplantation. In this issue of Clinical Kidney Journal, Hounkpatin et al. describe the association of socioeconomic deprivation with incidence, mortality and resolution of AKI in a large UK cohort. Investigating deprivation as a factor influencing either incidence or outcome of disease is challenging due to variations in measures of deprivation used and other confounding factors that may be contributing to the observed differences. In this editorial, we review the current literature examining the role of deprivation in renal disease.
Multi-component lipid emulsions, rather than soy-oil emulsions, prevent cholestasis by an unknown mechanism. Here, we quantified liver function, bile acid pools, and gut microbial and metabolite ...profiles in premature parenterally fed pigs given a soy-oil lipid emulsion, Intralipid (IL), a multi component lipid emulsion, SMOFlipid (SMOF), a novel emulsion with a modified fatty-acid composition experimental emulsion (EXP), or a control enteral diet (ENT) for 22 days. We assayed serum cholestasis markers, measured total bile acid levels in plasma, liver, and gut contents, and analyzed colonic bacterial 16S rRNA gene sequences and metabolomic profiles. Serum cholestasis markers (i.e., bilirubin, bile acids, and γ-glutamyl transferase) were highest in IL-fed pigs and normalized in those given SMOF, EXP, or ENT. Gut bile acid pools were lowest in the IL treatment and were increased in the SMOF and EXP treatments and comparable to ENT. Multiple bile acids, especially their conjugated forms, were higher in the colon contents of SMOF and EXP than in IL pigs. The colonic microbial communities of SMOF and EXP pigs had lower relative abundance of several gram-positive anaerobes, including Clostridrium XIVa, and higher abundance of Enterobacteriaceae than those of IL and ENT pigs. Differences in lipid and microbial-derived compounds were also observed in colon metabolite profiles. These results indicate that multi-component lipid emulsions prevent cholestasis and restore enterohepatic bile flow in association with gut microbial and metabolomic changes. We conclude that sustained bile flow induced by multi-component lipid emulsions likely exerts a dominant effect in reducing bile acid-sensitive gram-positive bacteria.
ObjectivesTo describe the incidence of adverse events (AEs), reactogenicity symptoms, menstrual changes and overall self-rated improvement in health and well-being after COVID-19 ...vaccination.DesignVAC4COVID is an ongoing prospective, active observational, post-authorisation cohort safety study (PASS) of UK-approved vaccines for COVID-19 disease.SettingThe study is conducted through a secure website (www.vac4covid.com) by MEMO Research, University of Dundee, UK.Participants16 265 adult (18 years or older) UK residents with a valid email address and internet access.InterventionsAny UK-authorised COVID-19 vaccination.Main outcome measuresThe outcomes reported in this interim analysis include AEs, reactogenicity-type AEs (headache, fatigue, muscle or joint pain, fever, nausea, dizziness or local vaccine reaction), menstrual changes and reported improvement in overall health and well-being.Results11 475 consented participants (mean age 54.8 years) provided follow-up data between 2 February and 5 October 2021 (mean follow-up duration 184 days), by which date 89.2% of participants had received two vaccine doses. 89.8% of 5222 participants who completed a follow-up questionnaire in the 7 days after any COVID-19 vaccination reported no AEs. The risk of experiencing any event (not necessarily vaccine-related) requiring hospitalisation was less than 0.2%. 43.7% of post-vaccination follow-up records reported improvement in health and well-being. Reactogenicity-type reactions were more common in the week after the first dose of ChAdOx1 than BNT162b2 (7.8% vs 1.6%), but this relationship was reversed after the second dose (1.3% vs 3.1%). 0.3% of women reported menstrual symptoms after vaccination; no differences between vaccine type or dose order were detected.ConclusionsThe study provides reassuring data on low rates of AEs after COVID-19 vaccination. Differences in reactogenicity-type AE profiles between ChAdOx1 and BNT162b2 and between first and second doses of these vaccines were observed.Trial registration numberISRCTN95881792; Pre-results.
Since the discovery of fibroblast growth factor (FGF)-19 over 20 years ago, our understanding of the peptide and its role in human biology has moved forward significantly. A member of a superfamily ...of paracrine growth factors regulating embryonic development, FGF19 is unique in that it is a dietary-responsive endocrine hormone linked with bile acid homeostasis, glucose and lipid metabolism, energy expenditure, and protein synthesis during the fed to fasted state. FGF19 achieves this through targeting multiple tissues and signaling pathways within those tissues. The diverse functional capabilities of FGF19 is due to the unique structural characteristics of the protein and its receptor binding in various cell types. This review will cover the current literature on the protein FGF19, its target receptors, and the biological pathways they target through unique signaling cascades.
Object
Glioblastoma multiforme (GBM) is the most common astrocytic brain tumor and carries a dire prognosis. Despite current therapeutic options—surgery, radiotherapy, and chemotherapy—survival ...varies from 11.3 to 14.6 months. A group of drugs known as histone deacetylase inhibitors (HDIs) has demonstrated a potentially beneficial role in cancer treatment, particularly in combination with other therapies. A drug that exhibits potential as an HDI is sodium valproate (VPA), which is frequently used to treat seizures in patients with cerebral neoplasms. The present study was undertaken to investigate the role of VPA as an antitumor agent in the management of patients with GBM.
Methods
A review was conducted in terms of how HDIs work, the use of antiepileptic drugs (AEDs), and the effects of AEDs on survival in a local cohort of patients diagnosed with GBM. The local cohort of patients was determined by reviewing the electronic histopathology and AED informatics systems. A meta-analysis of papers on the use of AEDs in GBM was also performed.
Results
The local cohort consisted of 236 patients with GBM, 210 of whom had complete data available for analysis, a median age of 62 years, and 1-year survival of 26%. Patients treated with AEDs had a significantly longer survival than those who were not (Mantel-Cox log-rank test 19.617, p < 0.001). Those treated with VPA had significantly longer survival than those who did not receive an AED (Mantel-Cox log-rank test 17.506, p < 0.001), and patients treated with VPA had a significantly longer survival than those who had received other AEDs (Mantel-Cox log-rank test 5.303, p < 0.02).
Conclusions
Authors of this study demonstrated evidence supporting the theory that VPA may benefit patients with GBM in terms of survival.
Treating pain in the context of chronic kidney disease (CKD) is challenging because of altered pharmacokinetics and pharmacodynamics, with an increased risk of toxicity and drug adverse events in ...this population. The aims of this systematic review and meta-analysis were to assess the prevalence of analgesic use and establish the risk of analgesics-related adverse events, in patients with CKD.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Medline, Embase, CINAHL, and CENTRAL were searched until January 2021. Random-effects meta-analyses and meta-regression were conducted to pool and summarise prevalence data and measures of association between analgesic use and adverse events.
Sixty-two studies relevant to the prevalence of analgesic use and 33 to analgesic-related adverse events were included, combining data on 2.3 and 3 million individuals, respectively. Pooled analyses found that 41% (95% confidence interval CI, 35–48) of the CKD population regularly use analgesia. The annual period prevalence was estimated at 50% for opioids and 21% for nonsteroidal anti-inflammatory drugs (NSAID). Overall, 20% and 7% of patients with CKD are on chronic opioid or NSAID therapy, respectively. Opioid use was associated with an increased risk of death (1.61; 95% CI, 1.12–2.31; n= 7, I2= 91%), hospitalisation (1.38; 95% CI, 1.32–1.45; n=2, I2=0%), and fractures (1.51; 95% CI, 1.16–1.96; n=3, I2=54%).
High levels of analgesic consumption and related serious adverse outcomes were found in patients with CKD. Consideration needs to be given to how these patients are assessed and managed in order to minimise harms and improve outcomes.
CRD42019156491 (PROSPERO).
Pain is a common but often undertreated symptom in patients with chronic kidney disease (CKD) with a much higher prevalence than in the general population. The aim of this systematic review was to ...synthesize all available quantitative evidence, in order to gain a better understanding of pain prevalence and pain types in patients with CKD. Four databases and the grey literature were searched until 15th January 2021. Random-effect meta-analyses were conducted with multiple subgroup analyses and meta-regressions to further explore the between-study heterogeneity. The quality of studies included was assessed using the Newcastle-Ottawa scale and the level of evidence was determined using the GRADE approach. One hundred sixteen studies reported data on 40,678 individuals. Results from meta-analyses yielded an overall prevalence of 60% (95% confidence interval 56-64) for pain, 48% (42-55) for chronic pain and 10% (6-15) for neuropathic pain. The prevalence of pain was lower among kidney transplant recipients 46% (37-56) compared with patients undergoing dialysis 63% (57-68) and those with non-dialysis CKD 63% (55-70). Musculoskeletal pain appeared to be the most common pain symptom among patients with CKD managed conservatively 42% (28-56) or receiving dialysis 45% (36-55) whilst abdominal pain was most prevalent in kidney transplant recipients 41% (7-86). Thus, all subgroups of patients with CKD suffer from a high burden of pain. Hence, greater awareness and recognition of this issue is vital to inform policy and service provision in this area.
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Abstract
Background and Aims
Pain is one of the commonest symptoms in patients with chronic kidney disease (CKD), with a large proportion undertreated. Managing chronic pain in CKD patients is ...problematic due to the altered pharmacokinetic and pharmacodynamic related to the reduced renal clearance making it challenging for physicians to find appropriate pain management strategies. The aim of this systematic review was to estimate the overall prevalence of different types of analgesia in patients with CKD and investigate their safety.
Method
The population comprised of all adult patients with CKD defined as an estimated glomerular filtration rate (eGFR) less than 60mL/min/1.73m2 which included CKD-non dialysis (CKD-ND), kidney transplant recipients (KTR), patients undergoing dialysis and those receiving palliative care. Analgesics investigated included opioids, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), gabapentinoids and acetaminophen. All studies reporting a prevalence of analgesic use and/or exploring the association between analgesic consumption and adverse outcomes were included. Medline, Embase, CENTRAL, CINAHL and the grey literature were searched up to December 2020. Random-effect meta-analyses were conducted using a Generalised Linear Mixed Model approach to estimate the overall prevalence of analgesics use in the CKD population, displayed in forest-plots. Evidence gathered from studies investigating the adverse outcomes related to analgesics consumption was synthesised in ‘harvest plots’.
Results
Sixty-three studies reporting a prevalence of analgesic use in patients with CKD were included. The overall prevalence of analgesic consumption was 42% (95% CI, 35-50%) in the general CKD population and 70% (95% CI, 62-68%) among those experiencing chronic pain. Seventeen studies reported a prevalence of opioid use with 36% (95% CI, 23-51%) of patients with CKD receiving at least one opioid prescription while 16% (95% CI, 11-22%) were on chronic opioid therapy. The chronic use of oxycodone, tramadol, propoxyphene, fentanyl and hydromorphone were 3.6%, 2.0%, 1.3%, 1.1% and 0.05% respectively. NSAIDs usage was estimated to 20% (95% CI, 15-25%) among patients with CKD (ibuprofen 4.6%, diclofenac 1.7%) and 8% (95% CI, 5-12%) took NSAIDs chronically, with a higher prevalence among dialysis patients (17%) compared with CKD-ND (7%) and KTR (5%) (p<0.01). Prevalence of gabapentin and pregabalin use was estimated at 10% and 3.5% respectively, on pooling of 3 studies. Finally, five studies yielded an overall prevalence of 24% for acetaminophen use.
Twenty studies assessing the association between analgesic use and adverse outcomes were included (Figure 1). Five of them demonstrated an association between opioid use and increased mortality, in all CKD subgroups; and three out of four studies reported more hospitalizations in opioid-users.Four studies highlighted an increased risk of gastro-intestinal bleeding associated with NSAIDs consumption and three studies found a significant association between gabapentin use and neurologic adverse events.
Conclusion
Only 70% of CKD patients experiencing chronic pain received an analgesic, suggesting that pain remains a significant public health burden. Despite limited evidence, opioids, NSAIDs and gabapentinoids seem to be associated with major adverse events. Their use requires cautious prescription, consideration of optimal dosage, and the development of therapeutic patient education to promote risk awareness. More evidence is warranted to better understand the adverse outcomes associated with long-term analgesic consumption and provide safe pain management strategies for patient with CKD.
The KDIGO (Kidney Disease: Improving Global Outcomes) definition of acute kidney injury (AKI) is frequently used in studies to examine the epidemiology of AKI. This definition is variably interpreted ...and applied to routinely collected health care data. The aim of this study was to examine this variation and to achieve consensus in how AKI should be defined for research using routinely collected health care data.
Scoping review via searching Medline and EMBASE for studies using health care data to examine AKI by using the KDIGO creatinine-based definition. An international panel of experts formed to participate in a modified Delphi process to attempt to generate consensus about how AKI should be defined when using routinely collected laboratory data.
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping reviews was followed. For the Delphi process, 2 rounds of questions were distributed via internet-based questionnaires to all participants with a prespecified cutoff of 75% agreement used to define consensus.
The scoping review found 174 studies that met the inclusion criteria. The KDIGO definition was inconsistently applied, and the methods for application were poorly described. We found 58 (33%) of papers did not provide a definition of how the baseline creatinine value was determined, and only 34 (20%) defined recovery of kidney function. Of 55 invitees to the Delphi process, 35 respondents participated in round 1, and 25 participated in round 2. Some consensus was achieved in areas related to how to define the baseline creatinine value, which patients should be excluded from analysis of routinely collected laboratory data, and how persistent chronic kidney disease or nonrecovery of AKI should be defined.
The Delphi panel members predominantly came from the United Kingdom, the United States, and Canada, and there were low response rates for some questions in round 1.
The current methods for defining AKI using routinely collected data are inconsistent and poorly described in the available literature. Experts could not achieve consensus for many aspects of defining AKI and describing its sequelae. The KDIGO guidelines should be extended to include a standardized definition for how AKI should be defined when using routinely collected data.
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