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Journal of Veterinary Internal Medicine Nov 2020Chronic kidney disease (CKD) and acute exacerbation of CKD (ACKD) are common in dogs.
BACKGROUND
Chronic kidney disease (CKD) and acute exacerbation of CKD (ACKD) are common in dogs.
OBJECTIVE
To characterize the etiology, clinical and laboratory findings, and short- and long-term prognosis of dogs with ACKD.
ANIMALS
One hundred dogs with ACKD.
METHODS
Medical records of dogs diagnosed with ACKD admitted to a veterinary teaching hospital were retrospectively reviewed.
RESULTS
The most common clinical signs included anorexia (84%), lethargy (77%), vomiting (55%) and diarrhea (37%). Presumptive etiology included inflammatory causes (30%), pyelonephritis (15%), ischemic causes (7%), other (3%), or unknown (45%). Median hospitalization time was 5 days (range, 2-29 days) and was significantly longer in survivors (6 days; range, 2-29 days) compared with nonsurvivors (4 days; range, 2-20 days; P < .001). Mortality rate was 35%. International Renal Interest Society (IRIS) acute kidney injury (AKI) grade at presentation was associated (P = .009) with short-term survival, but presumptive etiology was not (P = .46). On multivariable analysis; respiratory rate (P = .01), creatine kinase (CK) activity (P = .005) and serum creatinine concentration (SCR; P = .04) at presentation were associated with short-term outcome. Median survival time of dogs discharged was 105 days (95% confidence interval [CI], 25-184), with 35 and 8 dogs surviving up to 6 and 12 months, respectively. Presumptive etiology (P = .16) and SCR (P = .59) at discharge were not predictors of long-term survival.
CONCLUSION AND CLINICAL IMPORTANCE
Short-term outcome of dogs with ACKD is comparable to those with AKI but long-term prognosis is guarded. The IRIS AKI grade at presentation is a prognostic indicator of short-term outcome.
Topics: Acute Kidney Injury; Animals; Dog Diseases; Dogs; Hospitals, Animal; Hospitals, Teaching; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies
PubMed: 33044036
DOI: 10.1111/jvim.15931 -
Intensive Care Medicine Oct 2019Hemodynamic instability related to renal replacement therapy (HIRRT) is a frequent complication of all renal replacement therapy (RRT) modalities commonly used in the... (Review)
Review
Hemodynamic instability related to renal replacement therapy (HIRRT) is a frequent complication of all renal replacement therapy (RRT) modalities commonly used in the intensive care unit. HIRRT is associated with increased mortality and may impair kidney recovery. Our current understanding of the physiologic basis for HIRRT comes primarily from studies of end-stage kidney disease patients on maintenance hemodialysis in whom HIRRT is referred to as 'intradialytic hypotension'. Nonetheless, there are many studies that provide additional insights into the underlying mechanisms for HIRRT specifically in critically ill patients. In particular, recent evidence challenges the notion that HIRRT is almost entirely related to excessive ultrafiltration. Although excessive ultrafiltration is a key mechanism, multiple other RRT-related mechanisms may precipitate HIRRT and this could have implications for how HIRRT should be managed (e.g., the appropriate response might not always be to reduce ultrafiltration, particularly in the context of significant fluid overload). This review briefly summarizes the incidence and adverse effects of HIRRT and reviews what is currently known regarding the mechanisms underpinning it. This includes consideration of the evidence that exists for various RRT-related interventions to prevent or limit HIRRT. An enhanced understanding of the mechanisms that underlie HIRRT, beyond just excessive ultrafiltration, may lead to more effective RRT-related interventions to mitigate its occurrence and consequences.
Topics: Acute Kidney Injury; Fluid Shifts; Hemodynamics; Humans; Kidney; Kidney Failure, Chronic; Osmolar Concentration; Renal Replacement Therapy
PubMed: 31407042
DOI: 10.1007/s00134-019-05707-w -
Molecular Medicine (Cambridge, Mass.) Apr 2023Septic acute kidney injury (S-AKI) is the leading form of acute kidney failure among hospitalized patients, and the inflammatory response is involved in this process....
BACKGROUND
Septic acute kidney injury (S-AKI) is the leading form of acute kidney failure among hospitalized patients, and the inflammatory response is involved in this process. 4-octyl itaconate (4-OI) is a multi-target itaconate derivative with potent anti-inflammatory action. However, it remains elusive whether and how 4-OI contributes to the regulation of S-AKI.
METHODS
We employed a lipopolysaccharide (LPS)-induced AKI murine model and explored the potential renoprotective effect of 4-OI in vivo. In vitro experiments, BUMPT cells, a murine renal tubular cell line, were conducted to examine the effects of 4-OI on inflammation, oxidative stress, and mitophagy. Moreover, STAT3 plasmid was transfected in BUMPT cells to investigate the role of STAT3 signaling in the 4-OI-administrated state.
RESULTS
We demonstrate that 4-OI protects against S-AKI through suppressing inflammation and oxidative stress and enhancing mitophagy. 4-OI significantly reduced the levels of Scr, BUN, Ngal as well as the tubular injury in LPS-induced AKI mice. 4-OI restrained inflammation by reducing macrophage infiltration and suppressing the expression of IL-1β and NLRP3 in the septic kidney. 4-OI also reduced ROS levels, as well as cleaved caspase-3 and boosted antioxidants such as HO-1, and NQO1 in mice. In addition, the 4-OI treatment significantly promoted mitophagy. Mechanistically, 4-OI activated Nrf2 signaling and suppressed phosphorylated STAT3 in vivo and vitro. Molecular docking revealed the binding affinity of 4-OI towards STAT3. ML385, a specific Nrf2 inhibitor, partially repressed the anti-inflammatory and anti-oxidative effects of 4-OI and partially restricted the mitophagy induced by 4-OI in vivo and in vitro. Transfected with STAT3 plasmid partially suppressed mitophagy and the anti-inflammatory effect provoked by 4-OI in vitro.
CONCLUSION
These data suggest that 4-OI ameliorates LPS-induced AKI by suppressing inflammation and oxidative stress and enhancing mitophagy through the overactivation of the Nrf2 signaling pathway, and inactivation of STAT3. Our study identifies 4-OI as a promising pharmacologic for S-AKI.
Topics: Mice; Animals; Lipopolysaccharides; NF-E2-Related Factor 2; Molecular Docking Simulation; Signal Transduction; Acute Kidney Injury; Anti-Inflammatory Agents; Inflammation
PubMed: 37095432
DOI: 10.1186/s10020-023-00631-8 -
Critical Care (London, England) Jan 2020Acute kidney injury (AKI) is a common complication in burn patients admitted to the intensive care unit (ICU) associated with increased morbidity and mortality. Our... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute kidney injury (AKI) is a common complication in burn patients admitted to the intensive care unit (ICU) associated with increased morbidity and mortality. Our primary aim was to review incidence, risk factors, and outcomes of AKI in burn patients admitted to the ICU. Secondary aims were to review the use of renal replacement therapy (RRT) and impact on health care costs.
METHODS
We conducted a systematic search in PubMed, UpToDate, and NICE through 3 December 2018. All reviews in Cochrane Database of Systematic Reviews except protocols were added to the PubMed search. We searched for studies on AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE); Acute Kidney Injury Network (AKIN); and/or Kidney Disease: Improving Global Outcomes (KDIGO) criteria in burn patients admitted to the ICU. We collected data on AKI incidence, risk factors, use of RRT, renal recovery, length of stay (LOS), mortality, and health care costs.
RESULTS
We included 33 observational studies comprising 8200 patients. Overall study quality, scored according to the Newcastle-Ottawa scale, was moderate. Random effect model meta-analysis revealed that the incidence of AKI among burn patients in the ICU was 38 (30-46) %. Patients with AKI were almost evenly distributed in the mild, moderate, and severe AKI subgroups. RRT was used in 12 (8-16) % of all patients. Risk factors for AKI were high age, chronic hypertension, diabetes mellitus, high Total Body Surface Area percent burnt, high Abbreviated Burn Severity Index score, inhalation injury, rhabdomyolysis, surgery, high Acute Physiology and Chronic Health Evaluation II score, high Sequential Organ Failure Assessment score, sepsis, and mechanical ventilation. AKI patients had 8.6 (4.0-13.2) days longer ICU LOS and higher mortality than non-AKI patients, OR 11.3 (7.3-17.4). Few studies reported renal recovery, and no study reported health care costs.
CONCLUSIONS
AKI occurred in 38% of burn patients admitted to the ICU, and 12% of all patients received RRT. Presence of AKI was associated with increased LOS and mortality.
TRIAL REGISTRATION
PROSPERO (CRD42017060420).
Topics: Acute Kidney Injury; Burns; Humans; Incidence; Intensive Care Units
PubMed: 31898523
DOI: 10.1186/s13054-019-2710-4 -
Nature Aug 2019The early prediction of deterioration could have an important role in supporting healthcare professionals, as an estimated 11% of deaths in hospital follow a failure to...
The early prediction of deterioration could have an important role in supporting healthcare professionals, as an estimated 11% of deaths in hospital follow a failure to promptly recognize and treat deteriorating patients. To achieve this goal requires predictions of patient risk that are continuously updated and accurate, and delivered at an individual level with sufficient context and enough time to act. Here we develop a deep learning approach for the continuous risk prediction of future deterioration in patients, building on recent work that models adverse events from electronic health records and using acute kidney injury-a common and potentially life-threatening condition-as an exemplar. Our model was developed on a large, longitudinal dataset of electronic health records that cover diverse clinical environments, comprising 703,782 adult patients across 172 inpatient and 1,062 outpatient sites. Our model predicts 55.8% of all inpatient episodes of acute kidney injury, and 90.2% of all acute kidney injuries that required subsequent administration of dialysis, with a lead time of up to 48 h and a ratio of 2 false alerts for every true alert. In addition to predicting future acute kidney injury, our model provides confidence assessments and a list of the clinical features that are most salient to each prediction, alongside predicted future trajectories for clinically relevant blood tests. Although the recognition and prompt treatment of acute kidney injury is known to be challenging, our approach may offer opportunities for identifying patients at risk within a time window that enables early treatment.
Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Clinical Laboratory Techniques; Computer Simulation; Datasets as Topic; False Positive Reactions; Female; Humans; Male; Middle Aged; Pulmonary Disease, Chronic Obstructive; ROC Curve; Risk Assessment; Uncertainty; Young Adult
PubMed: 31367026
DOI: 10.1038/s41586-019-1390-1 -
Journal of the American College of... Mar 2020
Topics: Acute Kidney Injury; Humans
PubMed: 32192659
DOI: 10.1016/j.jacc.2020.01.022 -
Nature Communications Jun 2023Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for...
Acute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI.
Topics: Humans; Hospital Mortality; Risk Factors; Renal Dialysis; Acute Kidney Injury; Hospitals; Retrospective Studies
PubMed: 37349292
DOI: 10.1038/s41467-023-39474-6 -
Critical Care (London, England) Jan 2021Sepsis is a life-threatening condition accompanied by organ dysfunction subsequent to a dysregulated host response to infection. Up to 60% of patients with sepsis...
BACKGROUND
Sepsis is a life-threatening condition accompanied by organ dysfunction subsequent to a dysregulated host response to infection. Up to 60% of patients with sepsis develop acute kidney injury (AKI), which is associated with a poor clinical outcome. The pathophysiology of sepsis-associated AKI (sepsis-AKI) remains incompletely understood, but mitochondria have emerged as key players in the pathogenesis. Therefore, our aim was to identify mitochondrial damage in patients with sepsis-AKI.
METHODS
We conducted a clinical laboratory study using "warm" postmortem biopsies from sepsis-associated AKI patients from a university teaching hospital. Biopsies were taken from adult patients (n = 14) who died of sepsis with AKI at the intensive care unit (ICU) and control patients (n = 12) undergoing tumor nephrectomy. To define the mechanisms of the mitochondrial contribution to the pathogenesis of sepsis-AKI, we explored mRNA and DNA expression of mitochondrial quality mechanism pathways, DNA oxidation and mitochondrial DNA (mtDNA) integrity in renal biopsies from sepsis-AKI patients and control subjects. Next, we induced human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS) for 48 h to mimic sepsis and validate our results in vitro.
RESULTS
Compared to control subjects, sepsis-AKI patients had upregulated mRNA expression of oxidative damage markers, excess mitochondrial DNA damage and lower mitochondrial mass. Sepsis-AKI patients had lower mRNA expression of mitochondrial quality markers TFAM, PINK1 and PARKIN, but not of MFN2 and DRP1. Oxidative DNA damage was present in the cytosol of tubular epithelial cells in the kidney of sepsis-AKI patients, whereas it was almost absent in biopsies from control subjects. Oxidative DNA damage co-localized with both the nuclei and mitochondria. Accordingly, HUVECs induced with LPS for 48 h showed an increased mnSOD expression, a decreased TFAM expression and higher mtDNA damage levels.
CONCLUSION
Sepsis-AKI induces mitochondrial DNA damage in the human kidney, without upregulation of mitochondrial quality control mechanisms, which likely resulted in a reduction in mitochondrial mass.
Topics: Acute Kidney Injury; Adult; Aged; DNA Damage; DNA, Mitochondrial; Female; Humans; Kidney; Male; Middle Aged; Multiple Organ Failure; Sepsis
PubMed: 33494815
DOI: 10.1186/s13054-020-03424-1 -
Methodist DeBakey Cardiovascular Journal 2019This column is supplied by Amita Jain, MD, and Juan Jose Olivero, MD. Dr. Jain completed an internal medicine residency at Houston Methodist Hospital in Houston, Texas,... (Review)
Review
This column is supplied by Amita Jain, MD, and Juan Jose Olivero, MD. Dr. Jain completed an internal medicine residency at Houston Methodist Hospital in Houston, Texas, and recently joined a primary care practice in Delaware. She earned a Bachelor of Medicine and Surgery (MBBS) degree, with a distinction in microbiology, from Terna Medical College at the Maharashtra University of Health Sciences in Navi Mumbai, India. Before coming to Houston, Dr. Jain completed residency training in internal medicine and allied subspecialties at the Dr. Babasaheb Ambedkar Memorial Hospital in Byculla, Mumbai. Dr. Olivero is a nephrologist at Houston Methodist Hospital and a member of the hospital's Nephrology Training Program. He obtained his medical degree from the University of San Carlos School of Medicine in Guatemala, Central America, and completed his residency and nephrology fellowship at Baylor College of Medicine in Houston, Texas.
Topics: Acute Kidney Injury; Aristolochic Acids; Dietary Supplements; Disease Progression; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Kidney; Kidney Failure, Chronic; Prognosis; Risk Assessment; Risk Factors; Substance-Related Disorders; Time Factors
PubMed: 31687105
DOI: 10.14797/mdcj-15-3-228 -
BMJ Open Feb 2021Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the...
The timing of continuous renal replacement therapy initiation in sepsis-associated acute kidney injury in the intensive care unit: the CRTSAKI Study (Continuous RRT Timing in Sepsis-associated AKI in ICU): study protocol for a multicentre, randomised controlled trial.
INTRODUCTION
Acute kidney injury (AKI) is one of the most common organ dysfunction in sepsis, and increases the risk of unfavourable outcomes. Renal replacement therapy (RRT) is the predominant treatment for sepsis-associated AKI (SAKI). However, to date, no prospective randomised study has adequately addressed whether initiating RRT earlier will attenuate renal injury and improve the outcome of sepsis. The objective of the trial is to compare the early strategy with delayed strategy on the outcomes in patients with SAKI in the intensive care unit (ICU).
METHODS AND ANALYSIS
This is a large-scale, multicentre, randomised controlled trial about SAKI. In total, 460 patients with sepsis and evidence of AKI stage 2 of Kidney Disease Improving Global Outcomes (KDIGO) will be recruited and equally randomised into the early group and the delay group in a ratio of 1:1. In the early group, continuous RRT (CRRT) will be started immediately after randomisation. In the delay group, CRRT will initiated if at least one of the following criteria was met: stage 3 of KDIGO, severe hyperkalaemia, pulmonary oedema, blood urea nitrogen level higher than 112 mg/dL after randomisation. The primary outcome is overall survival in a 90-day follow-up period (90-day all-cause mortality). Other end points include 28-day, 60-day and 1-year mortality, recovery rate of renal function by day 28 and day 90, ICU and hospital length of stay, the numbers of CRRT-free days, mechanical ventilation-free days and vasopressor-free days, the rate of complications potentially related to CRRT, CRRT-related cost, and concentrations of inflammatory mediators in serum.
ETHICS AND DISSEMINATION
The trial has been approved by the Clinical Research and Application Institutional Review Board of the Second Affiliated Hospital of Guangzhou Medical University (2017-31-ks-01). Participants will be screened and enrolled from patients in the ICU with SAKI by clinicians, with no public advertisement for recruitment. Results will be disseminated in research journals and through conference presentations.
TRIAL REGISTRATION
NCT03175328.
Topics: Acute Kidney Injury; Continuous Renal Replacement Therapy; Humans; Intensive Care Units; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Renal Replacement Therapy; Sepsis
PubMed: 33608398
DOI: 10.1136/bmjopen-2020-040718