Cause Of Hospital-acquired AKI Research Articles

Berberine alleviated contrast-induced acute kidney injury by mitophagy-mediated NLRP3 inflammasome inactivation in a mice model

The incidence of contrast-induced acute kidney injury (CI-AKI) has escalated to become the third most prevalent cause of hospital-acquired AKI, with a lack of efficacious interventions. Berberine (BBR) possesses diverse pharmacological effects and exhibits renoprotective properties; however, limited knowledge exists regarding its impact on CI-AKI. Therefore, our study aimed to investigate the protective effects and underlying mechanisms of BBR on CI-AKI in a mice model, focusing on the nucleotide-binding oligomerization domain-like pyrin domain-containing protein 3 (NLRP3) inflammasome and mitophagy. The CI-AKI mice model was established by administering NG-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg), indomethacin (10 mg/kg), and iohexol (11 g/kg) following water deprivation. A pretreatment of 100 mg/kg of BBR was orally administered to the mice for two weeks. Renal injury markers, damage-associated molecular patterns (DAMPs), renal histopathology, mitochondrial morphology, autophagosomes, and potential mechanisms were investigated. BBR effectively reduced levels of renal injury biomarkers such as serum cystatin C, urea nitrogen, and creatinine, downregulated the protein level of kidney injury molecule 1 (KIM1), and mitigated renal histomorphological damage. Moreover, BBR reduced DAMPs, including high mobility group box-1 (HMGB1), heat shock protein 70 (HSP70), and uric acid (UA). It also alleviated oxidative stress and inflammatory factors such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β). Furthermore, the activation of NLRP3 inflammasome was attenuated in the BBR pretreatment group, as evidenced by both mRNA and protein levels. Electron microscopy and western blotting examination revealed that BBR mitigated mitochondrial damage and enhanced mitophagy. Additionally, BBR increased the P-AMPK/AMPK ratio. These findings indicated that BBR exerted a protective effect against CI-AKI by suppressing NLRP3 inflammasome activation and modulating mitophagy, providing a potential therapeutic strategy for its prevention.

JQ1 attenuates contrast-induced acute kidney injury through the upregulation of autophagy and inhibition of inflammation

PurposeContrast-induced acute kidney injury (CI-AKI) is the third most common cause of hospital-acquired AKI. However, there is a paucity of efficacious interventions for the management of CI-AKI. Here, we aim to investigate the effects of JQ1 in CI-AKI and provide theoretical data and a foundation for novel ideas for the clinical treatment of CI-AKI.MethodsIn this study, we performed in vivo and in vitro experiments with mice and HK2 cells injury models respectively. The levels of serum creatinine (Cr) and blood urea nitrogen (BUN) were determined by an automatic analyzer for the measurements of renal function. The viability of HK-2 cells was analyzed using the Cell Counting Kit-8 (CCK-8) kit. Additionally, the kidney changes in the mice were detected using histopathology (H&E) and immunofluorescent staining. The mRNA and protein expressions were assessed using Quantitative real-time PCR and western blot, respectively. Autophagy and apoptosis was analyzed by Transmission electron microscopy (TEM) and TUNEL assay respectively.ResultsThe results demonstrated that JQ1 exhibited potency of attenuating CI-AKI in mouse and HK2 cells. JQ1 increased the expression levels of Atg5, Atg7 and LC3B-II, and decreased the protein levels of p62 in the kidney and HK-2 cells. However, the combined use of JQ1 with chloroquine reversed the effects of JQ1. JQ1 also inhibited the inflammatory cells and downregulated the expression of some inflammatory cytokines (IL-6, IL-1β, TNF-α, and IFN-γ).ConclusionJQ1 protects against CI-AKI by promoting autophagy and inhibiting inflammation and JQ1 may be a promising therapeutic strategy for CI-AKI.

Urinary trehalase activitiy in contrast-associated acute kidney injury.

Contrast-associated acute kidney injury (CA-AKI) is the third most common cause of hospital-acquired AKI. Sensitive biomarkers can detect kidney injury early on because kidney damage begins immediately after the administration of a contrast medium. Due to its proximal tubule specificity, urinary trehalase can be a useful and early marker for detecting tubular damage. This study aimed to reveal the power of urinary trehalase activity in diagnosing CA-AKI. This is a prospective, observational, and diagnostic validity study. The study was performed in an academic research hospital's emergency department. Patients aged 18 years and over who underwent contrast-enhanced computed tomography in the emergency department were included in the study. Urinary trehalase activities were measured before and 12, 24, and 48 hours after the administration of a contrast medium. The primary outcome was the occurrence of CA-AKI, while the secondary outcomes were risk factors for CA-AKI, duration of hospital stay after contrast use, and the mortality rate in the hospital. A statistically significant difference between the CA-AKI group and the non-AKI group was found in the activities measured 12 hours after the administration of the contrast medium. Notably, the mean age of the patient group with CA-AKI was considerably higher than that of the non-AKI group. The risk of mortality was found to be remarkably more elevated in patients with CA-AKI. Further, there was a positive correlation between trehalase activity and HbA1c. In addition, a crucial correlation was found between trehalase activity and poor glycemic control. Urinary trehalase activity can be useful as a marker of acute kidney injuries due to proximal tubule damage. In the diagnosis of CA-AKI, especially the activity of trehalase in the 12th hour might be useful.

Radiocontrast-Induced Acute Kidney Injury Following Coronary Angiography and Percutaneous Coronary Intervention: A Retrospective Cohort Study

Despite the remarkable technological advances in coronary angiography (CA)/percutaneous coronary intervention (PCI) for diagnosis and treatment of coronary artery disease, the contrast-induced acute kidney injury (CI-AKI) is always an important cause of hospital-acquired AKI. Most local CI-AKI studies in Vietnam had small sample sizes and short-term follow-up of only 24-48 hours following CA or PCI intervention, resulting in controversial conclusions. We conducted a study of the incidence of CI-AKI during a longer follow-up time period and associated risk factors among adult patients undergoing CA/ PCI at Nguyen Tri Phuong University Public Hospital and Tam Duc Private Cardiology Center in Ho Chi Minh City, Vietnam between January 2014 and March 2015. All 320 patients with CA/PCI at the two hospitals were enrolled in a retrospective cohort study. Information on demographic data, treatment, and laboratory test results was collected from the patients’ records. The total cumulative incidence of CI-AKI at 24, 48, 72 and ≥72 hours following CA/PCI was 6.7%, 12%, 14% and 16.9% respectively. Prognostic factors for CI-AKI included an increase by 1 ml/min/1,73m² in clearance creatinine before the intervention (P = 0.006, Hazard Ratio (HR) = 0.970, 95%CI 0.949 – 0.991) and an increase by 1% in ejection fraction (P = 0.023, HR = 0.984, 95%CI 0.970 – 0.998). Delayed CI-AKI was not rare after CA/PCI intervention. Therefore, it is pivotal to monitor serum creatinine in a longer time after the intervention to timely detect CI-AKI. Also, information on risk factors such as emergency interventions, chronic kidney disease, and ejection fraction < 45% could assist in predicting CI-AKI development.

Inhibiting NLRP3 inflammasome attenuates apoptosis in contrast-induced acute kidney injury through the upregulation of HIF1A and BNIP3-mediated mitophagy

ABSTRACT The pathogenetic mechanism of contrast-induced acute kidney injury (CI-AKI), which is the third most common cause of hospital-acquired AKI, has not been elucidated. Previously, we demonstrated that renal injury and cell apoptosis were attenuated in nlrp3 knockout CI-AKI mice. Here, we investigated the mechanism underlying NLRP3 inhibition-mediated attenuation of apoptosis in CI-AKI. The RNA sequencing analysis of renal cortex revealed that the nlrp3 or casp1 knockout CI-AKI mice exhibited upregulated cellular response to hypoxia, mitochondrial oxidation, and autophagy when compared with the wild-type (WT) CI-AKI mice, which indicated that NLRP3 inflammasome inhibition resulted in the upregulation of hypoxia signaling pathway and mitophagy. The nlrp3 or casp1 knockout CI-AKI mice and iohexol-treated HK-2 cells with MCC950 pretreatment exhibited upregulated levels of HIF1A, BECN1, BNIP3, and LC3B-II, as well as enhanced colocalization of LC3B with BNIP3 and mitochondria, and colocalization of mitochondria with lysosomes. Additionally, roxadustat, a HIF prolyl-hydroxylase inhibitor, protected the renal tubular epithelial cells against iohexol-induced injury through stabilization of HIF1A and activation of downstream BNIP3-mediated mitophagy in vivo and in vitro. Moreover, BNIP3 deficiency markedly decreased mitophagy, and also significantly exacerbated apoptosis and renal injury. This suggested the protective function of BNIP3-mediated mitophagy in CI-AKI. This study elucidated a novel mechanism in which NLRP3 inflammasome inhibition attenuated apoptosis and upregulated HIF1A and BNIP3-mediated mitophagy in CI-AKI. Additionally, this study demonstrated the potential applications of MCC950 and roxadustat in clinical CI-AKI treatment. Abbreviations: BNIP3: BCL2/adenovirus E1B interacting protein 3; Ctrl: control; DAPI: 4′,6-diamidino-2-phenylindole dihydrochloride; EGLN2/PHD1: egl-9 family hypoxia-inducible factor 2; HIF1A: hypoxia inducible factor 1, alpha subunit; H-E: hematoxylin and eosin; IL18: interleukin 18; IL1B: interleukin 1 beta; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; mRNA: messenger RNA; NFKB/NF-κB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3: NLR family, pyrin domain containing 3; NS: normal saline; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RNA: ribonucleic acid; SEM: standard error of the mean; siRNA: small interfering RNA; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin, alpha; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; VDAC: voltage-dependent anion channel; WT: wild-type

Frequency of Risk Factors and Outcome of Hospital-Acquired Acute Kidney Injury.

Objective: To determine the frequencies of risk factors and the ultimate outcomes of ccute kidney injury (AKI) among hospitalized patients.Materials and methodology: This prospective, observational study was carried out from September 15, 2018, to March 14, 2019. All admitted patients, both male and female, with AKI, were included. Those with chronic kidney disease (CKD), small size echogenic kidneys (on ultrasonography, performed on admission), and recent history of urological intervention were excluded from the study. All patients were assessed for etiological factors (sepsis, gastroenteritis, surgical, and obstetrical) and outcome (improved, progression to CKD, or expired).Results: Out of a total of 230, most patients were aged between 20-50 years with a mean age of 38.99 ± 7.61 years. Males were 144 (62.61%) and females were 86 (37.39%). About 78 (33.91%) patients were hypertensive while 65 (28.26%) were diabetic. The cause of hospital-acquired AKI was found to be sepsis in most (71.73%, n=165) of the cases, followed by gastroenteritis (10.00%, n=23), surgical (9.56%, n=22), and obstetric (8.69%, n=20) causes. When the outcome was assessed, 10 (4.35%) patients expired, 154 (66.96%) improved completely, while 66 (28.69%) progressed to CKD.Conclusion: This study has shown that sepsis is the most common cause of AKI in patients admitted to the hospital. So we recommend that proper steps should be taken to ensure adequate hospital care for avoiding such outcomes in hospitalized patients, and further decrease mortality.

Clinical efficacy of Danhong injection in preventing contrast-induced acute kidney injury based on propensity score matching method.

Contrast-induced acute kidney injury (CI-AKI) is the third cause of hospital-acquired AKI, and existing clinical prevention and treatment measures such as hydration therapy and/or administration of antioxidants N-acetylcysteine treatment and other treatments still show little effect on the prevention and treatment of CI-AKI. This study aims to explore the effect of Danhong injection on prevention of CI-AKI. A total of 12 867 patients, who received coronary angiography, percutaneous coronary intervention, enhanced CT or vascular intervention in a tertiary hospital, were enrolled for this study. Among them, 423 in the treatment group received intravenous drip of Danhong injection, and 12 444 in the control group received routine medicine. Propensity score matching was conducted to balance confounding factors between the 2 groups and then the prevention effect of Danhong injection on CI-AKI was compared between them. A total of 423 pairs of patients were matched successfully. The incidence of CI-AKI in the non-Danhong control group was higher than that in the Danhong treatment group (5.7% vs 2.4%). The difference between the 2 groups was statistically significant (P<0.05). CI-AKI occurred maily in the Stage 1 in both the non-Danhong control group and the Danhong treatment group. The number of patients with Stage 1 of AKI in the control group was more than that in the treatment group, and the difference was statistically significant (P<0.05). The incidence of AKI in Stage 2 and Stage 3 was less in both groups, and the difference was not statistically significant (P>0.05). The results of this study support the use of Danhong injection in the prevention of the Stage 1 of CI-AKI.

MicroRNA-30c attenuates contrast-induced acute kidney injury by suppressing NLRP3 inflammasome

BackgroundsContrast-induced acute kidney injury (CIAKI) is the third most common cause of hospital-acquired AKI. It has been demonstrated that microRNA-30c (miR-30c) was upregulated in the CIAKI. However, the underlying mechanism remain unclear. MethodsThe CIAKI was induced in miniature pig. The expression profile of miR-30c in the kidney was evaluated by qPCR. The pathways regulated by miR-30c was identified by qPCR and western blot on renal tubular epithelial cells isolated from miniature pig. Finally, the potential therapeutic application of targeting miR-30c was assessed in the pig model of CIAKI. ResultsThe miR-30c was up-regulated in miniature pig with CIAKI. The miR-30c suppressed cell apoptosis, expression of NLRP3, the secretion of IL-1β and caspase-1 p10 on renal cells stimulated by iohexol in vitro. In the pig model, miR-30c inhibited the CIAKI development. ConclusionOur data demonstrated that the miR-30c induced by CIAKI could suppress cell apoptosis and kidney injury via targeting NLRP3. Therefore, targeting miR-30c might be a novel therapeutic candidate for CIAKI treatment and prevention.

Remote Ischemic Preconditioning and Contrast-Induced Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention: A Randomized Clinical Trial

BackgroundContrast-induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired AKI and a serious complication of percutaneous coronary intervention. ObjectiveThe aim of the present study was to assess whether remote ischemic preconditioning (RIPC) reduces the incidence of CI-AKI. MethodsWe conducted a prospective, randomized, sham-controlled clinical study. The study included 101 patients admitted to the Intensive Cardiac Therapy Clinic of Medical University of Lodz for elective percutaneous coronary intervention. The participants were randomly assigned in a 1:1 ratio to either a control group (n = 51) or an RIPC group (n = 50). In the latter, RIPC was achieved before percutaneous coronary intervention by 4 cycles of 5-minute inflation of a cuff on the left upper arm to 200 mm Hg followed by 5-minute deflation. In the control group, a deflated cuff was placed on the left arm for 40 minutes. Serum creatinine concentration was measured to check for the presence of CI-AKI within 48 to 72 hours of percutaneous coronary intervention. Serum neutrophil gelatinase-associated lipocalin level was also measured within 3 hours. ResultsCI-AKI occurred in 2 patients from the RIPC group (4%) and 3 patients from the control group (5.9%), but the difference was not significant (P = 0.98). The patients who developed CI-AKI also demonstrated increased serum neutrophil gelatinase-associated lipocalin concentrations (the area under the receiver operator characteristic curve = 0.97; 95% CI, 0.938–1.00; P < 0.00) and the optimal cutoff point value was 118.9 ng/mL. ConclusionsThe use of RIPC before elective percutaneous coronary intervention was not found to prevent CI-AKI. ClinicalTrials.gov identifier: NCT03761368. (Curr Ther Res Clin Exp. 2020; 81:XXX–XXX)

Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model

BackgroundContrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms. MethodsWe established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and β-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed. ResultsThe levels of Bun, Scr, serum and urinary RBP and β-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro. ConclusionsRA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.

Radiocontrast-Induced Acute Kidney Injury Following Coronary Angiography and Percutaneous Coronary Intervention: A Retrospective Cohort Study

Despite the remarkable technological advances in coronary angiography (CA)/percutaneous coronary intervention (PCI) for diagnosis and treatment of coronary artery disease, the contrast-induced acute kidney injury (CI-AKI) is always an important cause of hospital-acquired AKI. Most local CI-AKI studies in Vietnam had small sample sizes and short-term follow-up of only 24-48 hours following CA or PCI intervention, resulting in controversial conclusions. We conducted a study of the incidence of CI-AKI during a longer follow-up time period and associated risk factors among adult patients undergoing CA/ PCI at Nguyen Tri Phuong University Public Hospital and Tam Duc Private Cardiology Center in Ho Chi Minh City, Vietnam between January 2014 and March 2015. All 320 patients with CA/PCI at the two hospitals were enrolled in a retrospective cohort study. Information on demographic data, treatment, and laboratory test results was collected from the patients’ records. The total cumulative incidence of CI-AKI at 24, 48, 72 and ≥72 hours following CA/PCI was 6.7%, 12%, 14% and 16.9% respectively. Prognostic factors for CI-AKI included an increase by 1 ml/min/1,73m² in clearance creatinine before the intervention (P = 0.006, Hazard Ratio (HR) = 0.970, 95%CI 0.949 – 0.991) and an increase by 1% in ejection fraction (P = 0.023, HR = 0.984, 95%CI 0.970 – 0.998). Delayed CI-AKI was not rare after CA/PCI intervention. Therefore, it is pivotal to monitor serum creatinine in a longer time after the intervention to timely detect CI-AKI. Also, information on risk factors such as emergency interventions, chronic kidney disease, and ejection fraction < 45% could assist in predicting CI-AKI development.

Understanding and preventing contrast-induced acute kidney injury.

Contrast-induced acute kidney injury (CIAKI) occurs in up to 30% of patients who receive iodinated contrast media and is generally considered to be the third most common cause of hospital-acquired AKI. Accurate assessment of the incidence of CIAKI is obscured, however, by the use of various definitions for diagnosis, the different populations studied and the prophylactic measures put in place. A deeper understanding of the mechanisms that underlie CIAKI is required to enable reliable risk assessment for individual patients, as their medical histories will determine the specific pathways by which contrast media administration might lead to kidney damage. Here, we highlight common triggers that prompt the development of CIAKI and the subsequent mechanisms that ultimately cause kidney damage. We also discuss effective protective measures, such as rapidly acting oral hydration schemes and loop diuretics, in the context of CIAKI pathophysiology. Understanding of how CIAKI arises in different patient groups could enable a marked reduction in incidence and improved outcomes. The ultimate goal is to shape CIAKI prevention strategies for individual patients.

Urinary kidney injury molecule-1 as an early indicator to predict contrast-induced acute kidney injury in patients with diabetes mellitus undergoing percutaneous coronary intervention.

With the improvement of the skill level of coronary intervention, contrast agents are used more widely. As a result, contrast-induced acute kidney injury (CI-AKI) is currently the third leading cause of hospital-acquired AKI. Traditionally, AKI is defined by measuring an increase of the serum creatinine concentration (Scr). CI-AKI indicates impairment in renal function, which is diagnosed as an elevation in the SCr levels following intravascular injection of the contrast media. However, Scr is an insensitive indicator for detecting CI-AKI. The present study was designed to investigate whether human urinary kidney injury molecule-1 (KIM-1) is an early marker to predict CI-AKI in patients with diabetes mellitus undergoing percutaneous coronary intervention (PCI). The present study includes the general clinical data of 145 patients with diabetes mellitus who underwent PCI between March 1, 2013 and December 31, 2013. A non-ionic, low osmolarity contrast agent was used during the present study. The Scr levels and estimated glomerular filtration rate were measured prior to and within 24 and 48 h after the injection of contrast agents. Urinary samples were collected prior to and within 2, 6, 12, 24 and 48 h after the coronary interventional procedure. Simultaneously, the urinary KIM-1 values were measured using an ELISA kit. CI-AKI was diagnosed as an increase of ≥0.5 mg/dl or ≥25% in Scr concentration over baseline, 24-48 h after the procedure. In total, 19 of 145 (13.1%) patients exhibited CI-AKI. There was a significant difference (P<0.05) between the urinary KIM-1 levels measured 2, 6, 12, 24 and 48 h after the procedure and those prior to the procedure in the CI-AKI group. There was no significant difference between the Scr values measured 24 h after the procedure and those prior to the procedure. Evidently, using KIM-1 values to predict CI-AKI was <24 h earlier compared to using Scr values. The area under the receiver operating characteristic curve of KIM-1 24 h after the procedure was 0.856 and the 95% confidence interval of the corresponding area was 0.782-0.929. When the pivotal point of CI-AKI diagnosis was 6,327.755 pg/ml, the specificity was 85.7% and the sensitivity was 73.7%. Univariate analysis showed that the Scr concentration was positively correlated with the urinary KIM-1 level during the time prior to the procedure and 24 and 48 h after the procedure. In conclusion, the urinary KIM-1 may be a potential indicator for the early diagnosis of CI-AKI.

Incidence of contrast-induced acute kidney injury associated with diagnostic or interventional coronary angiography

Contrast-induced acute kidney injury (CI-AKI) represents an important cause of hospital-acquired AKI. The aim of this study was to evaluate the incidence of CI-AKI after coronary angiography (CA) or percutaneous coronary intervention (PCI) and the role of patient-/procedure-related risk factors. For 11 months, patients undergoing CA or PCI were prospectively evaluated for CI-AKI, and factors possibly affecting CI-AKI were analyzed. Statistical analysis was completed using Student's t-test, chi-square or Fisher exact test, and multivariate logistic regression. Among 585 consecutive patients, incidence of CI-AKI was 5.1% (n=30) and renal replacement therapy was required in 10% of those (n=3). Incidence of CI-AKI was higher in patients with anemia or chronic kidney disease (CKD) associated with diabetes. Basal hemoglobin was significantly lower in CI-AKI patients while Mehran score, contrast medium (CM) volume, contrast ratio (CM volume / maximum contrast dose) and ratio glomerular filtration rate (CM volume / GFR) were significantly higher. Multivariate analysis selected a higher contrast ratio as a factor independently associated with a higher risk of CI-AKI which otherwise appeared to be lower with increasing basal hemoglobin. The incidence of CI-AKI after CA or PCI was higher in patients with CKD associated with diabetes. Lower levels of basal hemoglobin appeared to be related to a higher risk of CI-AKI, and contrast media volume, especially if exceeding the dose adjusted for renal function, was a strong modifiable risk factor for CI-AKI.

Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury: Penny Wise or Pound Foolish?

Curbing the Use of Ultrasonography in the Diagnosis of Acute Kidney Injury: Penny Wise or Pound Foolish?