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-1ß). 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.

Contrast-induced acute kidney injury: a review of definition, pathogenesis, risk factors, prevention and treatment.

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired AKI, which seriously threatens the health of patients. To date, the precise pathogenesis of CI-AKI has remained not clear and may be related to the direct cytotoxicity, hypoxia and ischemia of medulla, and oxidative stress caused by iodine contrast medium, which have diverse physicochemical properties, including cytotoxicity, permeability and viscosity. The latest research shows that microRNAs (miRNAs) are also involved in apoptosis, pyroptosis, and autophagy which caused by iodine contrast medium (ICM), which may be implicated in the pathogenesis of CI-AKI. Unfortunately, effective therapy of CI-AKI is very limited at present. Therefore, effective prevention of CI-AKI is of great significance, and several preventive options, including hydration, antagonistic vasoconstriction, and antioxidant drugs, have been developed. Here, we review current knowledge about the features of iodine contrast medium, the definition, pathogenesis, molecular mechanism, risk factors, prevention and treatment of CI-AKI.

The relationship between perioperative serum albumin and contrast-induced acute kidney injury in patients after percutaneous coronary intervention.

OBJECTIVE: Contrast-induced acute kidney injury (CI-AKI) is a common complication in patients undergoing percutaneous coronary intervention (PCI). Studies have shown that perioperative serum albumin levels may play a role in the occurrence of CI-AKI. In this study, we aimed to investigate the effect of perioperative serum albumin (delta albumin or &Alb) levels on the occurrence and long-term prognosis of CI-AKI patients after PCI. METHODS: A total of 959 patients who underwent PCI between January 2017 and January 2019 were selected for this study. A receiver operating characteristic curve was used to determine the optimal cut-off value of the &Alb level for predicting CI-AKI after PCI. Patients were divided into two groups based on the optimal cut-off value: the high &Alb group (&Alb ≥ 4.55 g/L) and the control group (&Alb < 4.55 g/L). The incidences of CI-AKI and major adverse cardiac events (MACEs, including all-cause death, nonfatal myocardial infarction, and target vessel revascularization) were compared between the groups. Cox regression analysis was used to identify predictors of long-term prognosis after PCI. RESULTS: Of the 959 patients, 147 (15.3%) developed CI-AKI after PCI. The CI-AKI group had a greater level of &Alb than did the non-CI-AKI group [(6.14 (3.90-9.10) versus 3.48 (4.31-6.57), P < 0.01)]. The incidence of CI-AKI in the high &Alb group was significantly greater than that in the low group (23.6% versus 8.3%, P < 0.01). After a 1-year follow-up, the incidence of MACEs was significantly greater in the high &Alb group than in the low group (18.6% versus 14.5%, P = 0.030). Cox regression analysis confirmed that CI-AKI was an independent predictor of MACEs at the 1-year follow-up (HR 1.43, 95% CI 1.04-1.96, P = 0.028). In addition, patients with low preoperative serum albumin levels had s significantly greater incidence of MACEs than did those with high preoperative serum albumin levels (23.2% versus 19.5%, P = 0.013). CONCLUSION: In summary, high baseline &Alb levels are an independent risk factor for CI-AKI in patients after PCI. The occurrence of CI-AKI in the perioperative period is also an independent predictor of long-term prognosis after PCI. These findings highlight the importance of monitoring &Alb levels and taking steps to prevent CI-AKI in patients undergoing PCI.

CUX1 attenuates the apoptosis of renal tubular epithelial cells induced by contrast media through activating the PI3K/AKT signaling pathway.

OBJECTIVE: Contrast media (CM) is a commonly applied drug in medical examination and surgery. However, contrast-induced acute kidney injury (CIAKI) poses a severe threat to human life and health. Notably, the CUT-like homeobox 1 (CUX1) gene shows protective effects in a variety of cells. Therefore, the objective of this study was to provide a new target for the treatment of CIAKI through exploring the role and possible molecular mechanism of CUX1 in CIAKI. METHOD: Blood samples were collected from 20 patients with CIAKI and healthy volunteers. Human kidney 2 (HK-2) cells were incubated with 200 mg/mL iohexol for 6 h to establish a contrast-induced injury model of HK-2 cells. Subsequently, qRT-PCR was used to detect the relative mRNA expression of CUX1; CCK-8 and flow cytometry to assess the proliferation and apoptosis of HK-2 cells; the levels of IL(interleukin)-1ß, tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) in cells and lactate dehydrogenase (LDH) activity in cell culture supernatant were detect; and western blot to observe the expression levels of CUX1 and the PI3K/AKT signaling pathway related proteins [phosphorylated phosphoinositide 3-kinase (p-PI3K), PI3K, phosphorylated Akt (p-AKT), AKT]. RESULTS: CUX1 expression was significantly downregulated in blood samples of patients with CIAKI and contrast-induced HK-2 cells. Contrast media (CM; iohexol) treatment significantly reduced the proliferation of HK-2 cells, promoted apoptosis, stimulated inflammation and oxidative stress that caused cell damage. CUX1 overexpression alleviated cell damage by significantly improving the proliferation level of HK-2 cells induced by CM, inhibiting cell apoptosis, and reducing the level of LDH in culture supernatant and the expression of IL-1ß, TNF-α and MDA in cells. CM treatment significantly inhibited the activity of PI3K/AKT signaling pathway activity. Nevertheless, up-regulating CUX1 could activate the PI3K/AKT signaling pathway activity in HK-2 cells induced by CM. CONCLUSION: CUX1 promotes cell proliferation, inhibits apoptosis, and reduces inflammation and oxidative stress in CM-induced HK-2 cells to alleviate CM-induced damage. The mechanism of CUX1 may be correlated with activation of the PI3K/AKT signaling pathway.

Berberine ameliorates contrast-induced acute kidney injury by regulating HDAC4-FoxO3a axis-induced autophagy: In vivo and in vitro.

In hospitals, contrast-induced acute kidney injury (CI-AKI) is a major cause of renal failure. This study evaluates berberine's (BBR) renal protection and its potential HDAC4 mechanism. CI-AKI in rats was induced with 10 mL kg-1 ioversol. Rats were divided into five groups: Ctrl, BBR, CI-AKI, CI-AKI + BBR, and CI-AKI + Tasq. The renal function of CI-AKI rats was determined by measuring serum creatinine and blood urea nitrogen. Histopathological changes and apoptosis of renal tubular epithelial cells were observed by HE and terminal deoxynucleotidyl transferase (TdTase)-mediated dUTP-biotin nick end labeling (TUNEL) staining. Transmission electron microscopy was used to observe autophagic structures. In vitro, a CI-AKI cell model was created with ioversol-treated HK-2 cells. Treatments included BBR, Rapa, HCQ, and Tasq. Analyses focused on proteins and genes associated with kidney injury, apoptosis, autophagy, and the HDAC4-FoxO3a axis. BBR showed significant protective effects against CI-AKI both in vivo and in vitro. It inhibited apoptosis by increasing Bcl-2 protein levels and decreasing Bax levels. BBR also activated autophagy, as indicated by changes in autophagy-related proteins and autophagic flux. The study further revealed that the contrast agent ioversol increased the expression of HDAC4, which led to elevated levels of phosphorylated FoxO3a (p-FoxO3a) and acetylated FoxO3a (Ac-FoxO3a). However, BBR inhibited HDAC4 expression, resulting in decreased levels of p-FoxO3a and Ac-FoxO3a. This activation of autophagy-related genes, regulated by the transcription factor FoxO3a, played a role in BBR's protective effects. BBR, a traditional Chinese medicine, shows promise against CI-AKI. It may counteract CI-AKI by modulating HDAC4 and FoxO3a, enhancing autophagy, and limiting apoptosis.

Biomarkers in Contrast-Induced Acute Kidney Injury: Towards A New Perspective.

Contrast-Induced Acute Kidney Injury (CI-AKI) remains a frequent iatrogenic condition since radiological procedures using intra-vascular iodinated contrast media (CM) are being widely administered for diagnostic and therapeutic purposes. Despite the improvement of the medical healthcare system worldwide, CI-AKI is still associated with direct short-term and indirect long-term outcomes including increased morbidity and mortality, especially in patients with underlying pre-existing renal function impairment, cardiovascular disease, or diabetes that could rapidly progress into Chronic Kidney Disease. Although the RIFLE (Risk, Injury, Failure, Loss, End-Stage Kidney Disease), AKIN (Acute Kidney Injury Network), and KDIGO (Kidney Disease Improving Global Outcomes) clinical criteria and recommendation guidelines are based on traditional "gold standard" biomarkers known as serum creatinine, glomerular filtration rate, and urinary output, new reliable serum and urinary biomarkers are still needed for an effective unified diagnostic strategy for AKI. Starting from previous and recent publications on the benefits and limitations of validated biomarkers responding to kidney injury, glomerular filtration, and inflammation among others, this review unravels the role of new emerging biomarkers used alone or in combination as reliable tools for early diagnosis and prognosis of CI-AKI, taking into account patients and procedures-risk factors towards a new clinical perspective.

Circulating mitochondrial dysfunction as an early biomarker for contrast media-induced acute kidney injury in chronic kidney disease patients.

Contrast-induced acute kidney injury (CI-AKI) is the common hospitalized acute kidney injury (AKI). However, the diagnosis by serum creatinine might not be early enough. Currently, the roles of circulating mitochondria in CI-AKI are still unclear. Since early detection is crucial for treatment, the association between circulating mitochondrial function and CI-AKI was tested as a potential biomarker for detection of CI-AKI. Twenty patients with chronic kidney disease (CKD) undergoing percutaneous coronary intervention (PCI) were enrolled. Blood and urine samples were obtained at the time of PCI, and 6, 24, 48 and 72 h after PCI. Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) were measured. Oxidative stress, inflammation, mitochondrial function, mitochondrial dynamics and cell death were determined from peripheral blood mononuclear cells. Forty percent of patients developed AKI. Plasma NGAL levels increased after 24 h after receiving contrast media. Cellular and mitochondrial oxidative stress, mitochondrial dysfunction and decreased mitochondrial fusion occurred at 6 h following contrast media exposure. Subgroup of AKI had higher %necroptosis cells and TNF-α mRNA expression than subgroup without AKI. Collectively, circulating mitochondrial dysfunction could be an early predictive biomarker for CI-AKI in CKD patients receiving contrast media. These findings provide novel strategies to prevent CI-AKI according to its pathophysiology.

A novel explainable online calculator for contrast-induced AKI in diabetics: a multi-centre validation and prospective evaluation study.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI), contrast-induced acute kidney injury (CIAKI) is a frequent complication, especially in diabetics, and is connected with severe mortality and morbidity in the short and long term. Therefore, we aimed to develop a CIAKI predictive model for diabetic patients. METHODS: 3514 patients with diabetes from four hospitals were separated into three cohorts: training, internal validation, and external validation. We developed six machine learning (ML) algorithms models: random forest (RF), gradient-boosted decision trees (GBDT), logistic regression (LR), least absolute shrinkage and selection operator with LR, extreme gradient boosting trees (XGBT), and support vector machine (SVM). The area under the receiver operating characteristic curve (AUC) of ML models was compared to the prior score model, and developed a brief CIAKI prediction model for diabetes (BCPMD). We also validated BCPMD model on the prospective cohort of 172 patients from one of the hospitals. To explain the prediction model, the shapley additive explanations (SHAP) approach was used. RESULTS: In the six ML models, XGBT performed best in the cohort of internal (AUC: 0.816 (95% CI 0.777-0.853)) and external validation (AUC: 0.816 (95% CI 0.770-0.861)), and we determined the top 15 important predictors in XGBT model as BCPMD model variables. The features of BCPMD included acute coronary syndromes (ACS), urine protein level, diuretics, left ventricular ejection fraction (LVEF) (%), hemoglobin (g/L), congestive heart failure (CHF), stable Angina, uric acid (umol/L), preoperative diastolic blood pressure (DBP) (mmHg), contrast volumes (mL), albumin (g/L), baseline creatinine (umol/L), vessels of coronary artery disease, glucose (mmol/L) and diabetes history (yrs). Then, we validated BCPMD in the cohort of internal validation (AUC: 0.819 (95% CI 0.783-0.855)), the cohort of external validation (AUC: 0.805 (95% CI 0.755-0.850)) and the cohort of prospective validation (AUC: 0.801 (95% CI 0.688-0.887)). SHAP was constructed to provide personalized interpretation for each patient. Our model also has been developed into an online web risk calculator. MissForest was used to handle the missing values of the calculator. CONCLUSION: We developed a novel risk calculator for CIAKI in diabetes based on the ML model, which can help clinicians achieve real-time prediction and explainable clinical decisions.

The effect of perioperative diuretic administration on acute kidney injury in patients with acute myocardial infarction after percutaneous coronary intervention: a real-world retrospective study.

PURPOSE: The relationship between diuretic use and contrast-induced acute kidney injury (CI-AKI) after contrast exposure remains unclear. In this study, we conducted a retrospective analysis using propensity score matching (PSM) to investigate the effect of perioperative diuretic administration on contrast-induced acute kidney injury (CI-AKI) in patients with acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI). METHODS: A total of 1894 patients with AMI who underwent PCI were retrospectively analyzed using PSM and multivariate models. Depending on whether diuretics were used, the patients were divided into two groups: the perioperative diuretic group (497 patients, 26.2%) and the non-diuretic group (1397 patients, 73.8%). And the relationship between perioperative diuretic administration and CI-AKI was evaluated by multiple regression models. Furthermore, Kaplan Meier survival curve ratio was used to evaluate and compare overall postoperative survival between the two groups. RESULTS: Most patients who received diuretics were older (67 vs. 60 years, respectively, p < 0.001) and women (22.5% vs. 15.2%, p < 0.001) and had combined hypertension (62.8% vs. 47%, p < 0.001), atrial fibrillation (5.4% vs. 1.8%, p < 0.001), stroke (9.3% vs. 4.9%, p < 0.001), and diabetes mellitus (33.4% vs. 23.6%, p < 0.001) compared to those who did not. After the baseline characteristics were balanced using the PSM model, no significant difference was observed in the incidence of postoperative CI-AKI (22.7% vs. 19.5%, p = 0.356) and major cardiovascular adverse events (21.5% vs. 18.7%, p = 0.398). Multiple regression analysis showed no association between perioperative diuretic administration and postoperative CI-AKI occurrence (odds ratio: 1.14, 95% confidence interval: 0.86-1.51, p = 0.371). Further subgroup analysis and sensitivity analysis confirmed the above findings. CONCLUSION: We found no significant association between perioperative diuretic administration and postoperative CI-AKI in patients with AMI who underwent PCI.

Prevention of contrast induced-acute kidney injury using coenzyme Q10 in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

PURPOSE: We assessed the potential effect of CoQ10 administration for the prevention of contrast induced-acute kidney injury (CI-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). METHODS: One hundred fifty STEMI patients who were candidates for primary PCI, along with intravenous saline hydration, randomly received a placebo or CoQ10. CoQ10 was administrated orally, 400 mg before the procedure and 200 mg twice daily after the procedure for three consecutive days. Serum creatinine concentration and corresponding creatinine clearance (estimated by the CKD Epidemiology Collaboration (CKD-EPI) creatinine equation) were measured at baseline and 24, 48, and 72 h after primary PCI. Furthermore, the serum level of superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA) was measured before and 72 h after primary PCI. RESULTS: The mean serum creatinine concentration before contrast administration was similar in the two groups (0.98 ± 0.08 versus 0.99 ± 0.09 mg/dL). While in both study groups, compared to baseline, the mean serum creatinine concentration increased at 48 and 72 h after contrast exposure, the CoQ10 group showed a lower serum creatinine concentration than the placebo group (P-value = 0.017 and 0.004, respectively). However, comparing the mean values of creatinine clearance between the groups at the study time points did not demonstrate a statistically significant difference. CI-AKI, defined as a > 25% or 0.5 mg/dL increase in baseline serum creatinine concentration, occurred in 8.00% of the cases in the CoQ10 group versus 20.00% in the placebo group (P-value = 0.034). Furthermore, at 72 h, the CoQ10-treated group exhibited higher serum levels of SOD and TAC and a lower MDA level than the placebo-treated group. CONCLUSIONS: Our research's findings proposed CoQ10 supplementation as an adjuvant to saline hydration as a preventive approach against CI-AKI. TRIAL REGISTRATION: The trial was registered at Iranian Registry of Clinical Trials ( https://www.irct.ir/trial/60435 , identifier code: IRCT20120215009014N414). Registration date: 2021-12-29.

Renoprotective effect of febuxostat on contrast-induced acute kidney injury in chronic kidney disease patients stage 3: randomized controlled trial.

INTRODUCTION: Contrast-induced acute kidney injury (CI-AKI) is known to be a complication of using intravascular contrast injection. Unfortunately, it is associated with adverse outcomes such as prolonged length of hospitalization and increased burden of health care costs. So, we aimed to determine the efficacy of febuxostat in the prevention of contrast-induced acute kidney injury among patients with chronic kidney disease Stage 3 performing percutaneous coronary intervention (PCI). METHODS: In a randomized controlled trial we enrolled 120 CKD stage 3 Patients with acute coronary syndrome referred to the cardiology department Ain-Shams University hospital for performing PCI and stenting. Patients were randomly assigned to two arms: Group I (study group): Included 60 patients who received Febuxostat added to the traditional treatment (IV hydration and N-acetylcysteine). The patients received Feburic 80 mg within 6-18 h before and within 6-18 h after the coronary intervention (a time gap of 24 h between two doses). Group II (control group): included 60 patients who received only traditional treatment. RESULTS: The incidence of AKI was higher in the control group with a statistically significant difference. We found that Independent Significant risk factors that led to AKI were febuxostate avoidance, DM, high urea level, high creatinine level, CKD stage 3B, high Mehran score and high AKI risk. CONCLUSION: We demonstrated that febuxostat has a Reno protective effect and it can help to reduce the incidence CI-AKI in CKD patients stage 3 performing PCI.

The intellectual base and global trends in contrast-induced acute kidney injury: a bibliometric analysis.

Contrast-induced acute kidney injury (CI-AKI) has become the third leading cause of hospital-acquired kidney injury. A comprehensive analysis of the current state of research in the field of CI-AKI will help to reveal trends and hot topics in the field. To date, there are no published bibliometric analyses related to CI-AKI studies. Here, we analyze the relevant literature since the emergence of the concept and provide valuable insights. The literature was collected from the Web of Science Core Collection. The data were analyzed visually using CiteSpace and VOSviewer software. We collected a total of 4775 papers, with the United States and Guangdong Acad Med Sci as the major publishing powers in terms of country/region and institution. J AM COLL CARDIOL was the journal with the most published and cocited articles. Cluster analysis showed that clinical trials are the current research hotspot. The areas of risk assessment, prevention strategies, risk factors, and vascular lesions have been popular in recent years. Research on the mechanism of injury in CI-AKI will be the focus of future research, which will be crucial to reduce the clinical incidence of CI-AKI. In summary, this study provides a comprehensive analysis of the development process in the field of CI-AKI and discusses future research directions based on the analysis of objective data from many studies on CI-AKI.

The Potential Biotherapeutic Targets of Contrast-Induced Acute Kidney Injury.

Contrast-induced acute kidney injury (CI-AKI) is manifested by an abrupt decline in kidney function as a consequence of intravascular exposure to contrast media. With the increased applicability of medical imaging and interventional procedures that utilize contrast media for clinical diagnosis, CI-AKI is becoming the leading cause of renal dysfunction. The pathophysiological mechanism associated with CI-AKI involves renal medullary hypoxia, the direct toxicity of contrast agents, oxidative stress, apoptosis, inflammation, and epigenetic regulation. To date, there is no effective therapy for CI-AKI, except for the development of strategies that could reduce the toxicity profiles of contrast media. While most of these strategies have failed, evidence has shown that the proper use of personalized hydration, contrast medium, and high-dose statins may reduce the occurrence of CI-AKI. However, adequate risk predication and attempts to develop preventive strategies can be considered as the key determinants that can help eliminate CI-AKI. Additionally, a deeper understanding of the pathophysiological mechanism of CI-AKI is crucial to uncover molecular targets for the prevention of CI-AKI. This review has taken a step further to solidify the current known molecular mechanisms of CI-AKI and elaborate the biomarkers that are used to detect early-stage CI-AKI. On this foundation, this review will analyze the molecular targets relating to apoptosis, inflammation, oxidative stress, and epigenetics, and, thus, provide a strong rationale for therapeutic intervention in the prevention of CI-AKI.

Feasibility of Ultra-Low Volume Contrast-Saline Mixture Injection With Dual-Flow Technique in a Pre-TAVI Computed Tomography Angiography.

BACKGROUND: To explore the feasibility and image quality of ultra-low volume contrast-saline mixture injection with dual-flow injection technique in a computed tomography angiography (CTA) protocol in patients scheduled for transcatheter aortic valve implantation (TAVI). METHODS: Forty (40) TAVI candidates underwent investigation with CTA using a third-generation dual-source CT scanner between September and November 2020. Different volumes of a monophasic contrast-saline mixture at an 80:20 ratio were administered at an infusion rate of 3 mL/s in 20 patients (group A). The injected volume was based on patient body mass index (BMI): 50 mL if BMI <29 kg/m2 and 63 mL if BMI >29 kg/m2. The other 20 patients (group B)-the control cases-received a total of 65 mL of contrast medium (CM), in multiphasic injections at different flow rates, followed by 10 mL of saline. The images that were obtained were prospectively evaluated for image quality, vessel attenuation (HU), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and estimated radiation dose. RESULTS: Image quality of the aortic root and ilio-femoral vessels was diagnostic in all patients. Vascular attenuation was >200 HU and CNR >3 at any vessel level. CONCLUSIONS: Data from this study suggest that a monophasic ultra-low volume contrast-saline mixture injection with a dual-flow technique can provide clear visualisation of the aortic root and ilio-femoral vessels in pre-TAVI CTA, which is comparable with a standard multiphasic volume injection protocol.

Research progress on animal models of contrast-induced acute kidney injury. / é€ å½±å‰‚è¯±å¯¼çš„æ€¥æ€§è‚¾æŸä¼¤åŠ¨ç‰©æ¨¡åž‹çš„ç ”ç©¶è¿›å±•.

Contrast-induced acute kidney injury (CI-AKI) refers to acute kidney injury that occurs after intravascular contrast media is applied. It is the third most common cause for acute renal failure in hospitalized patients and can cause severe renal impairment and adverse cardiovascular outcomes. In severe cases, it can even lead to the death of the patient. Due to its complicated pathogenesis, the pathogenesis of CI-AKI has not yet been elucidated. Therefore, it is of great significance to further study the pathogenesis for the prevention of CI-AKI. Moreover, a good animal model of CI-AKI is an important tool for in-depth research on the pathogenesis of acute kidney injury induced by contrast agents.

Effect of contrast administration on the renal function of predialysis patients undergoing fistuloplasty.

OBJECTIVE: The aim of this study was to investigate if administration of iodinated contrast during endovascular interventions in arteriovenous fistula (AVF) in patients not requiring dialysis (predialysis patients) (1) negatively affects their renal function and (2) if oral hydration has a protective effect. METHODS: All pre-dialysis patients who underwent endovascular interventions in AVF between August 2010 and April 2019 were included in the study. During the procedures, 35 to 50 mL of Iodixanol were administered. A pre-hydration protocol was introduced in March 2015. Data were grouped before and after this date. The difference between pre- and post-contrast estimated glomerular filtration rate (eGFR) and the difference between the eGFR of hydrated and non-hydrated groups were calculated. RESULTS: Eighty-four patients who underwent 151 procedures were included in the study. In 60.3% of procedures, a mean decrease of 1.35 mL/min/1.73 m2 in eGFR was noted (95% confidence interval [CI], 1.02-1.69 mL/min/1.73 m2), whereas in 35.1% of procedures, there was a mean increase of 1.06 mL/min/1.73 m2 (95% CI, 0.84-1.28 mL/min/1.73 m2). The mean difference between pre- and post-procedure eGFR was -0.44 mL/min/1.73 m2 (95% CI, -0.72 to -0.16 mL/min/1.73 m2; P = .002). Oral hydration was associated with a smaller mean change in eGFR of -0.32 mL/min/1.73 m2 (95% CI, -0.62 to -0.03 mL/min/1.73 m2) compared with the non-hydrated group, with mean change of -0.47 mL/min/1.73 m2 (95% CI, -0.91 to -0.03 mL/min/1.73 m2), but this was not statistically significant (P = .586). CONCLUSIONS: This study demonstrates that administration of up to 50 mL of iodinated contrast for endovascular interventions in AVF in predialysis patients has minimal adverse effect on the eGFR with questionable clinical significance. In addition, oral hydration before and after the procedure has only a mild protective effect against a decrease in eGFR.

A multiple-metabolites model to predict preliminary renal injury induced by iodixanol based on UHPLC/Q-Orbitrap-MS and 1H-NMR.

BACKGROUND & AIMS: There are some problems, such as unclear pathological mechanism, delayed diagnosis, and inaccurate therapeutic target of Contrast-induced acute kidney injury (CI-AKI). It is significantly important to find biomarkers and therapeutic targets that can indicate renal injury in the early stage of CI-AKI. This study aims to establish a multiple-metabolites model to predict preliminary renal injury induced by iodixanol and explore its pathogenesis. METHODS: Both UHPLC/Q-Orbitrap-MS and 1H-NMR methods were applied for urine metabolomics studies on two independent cohorts who suffered from a preliminary renal injury caused by iodixanol, and the multivariate statistical analysis and random forest (RF) algorithm were used to process the related date. RESULTS: In the discovery cohort (n = 169), 6 metabolic markers (leucine, indole, 5-hydroxy-L-tryptophan, N-acetylvaline, hydroxyhexanoycarnine, and kynurenic acid) were obtained by the cross-validation between the RF and liquid chromatography-mass spectrometry (LC-MS). Secondly, the 6 differential metabolites were confirmed by comparison of standard substance and structural identification of 1H-NMR. Subsequently, the multiple-metabolites model composed of the 6 biomarkers was validated in a validation cohort (n = 165). CONCLUSIONS: The concentrations of leucine, indole, N-acetylvaline, 5-hydroxy-L-tryptophan, hydroxyhexanoycarnitine and kynurenic acid in urine were proven to be positively correlated with the degree of renal injury induced by iodixanol. The multiple-metabolites model based on these 6 biomarkers has a good predictive ability to predict early renal injury caused by iodixanol, provides treatment direction for injury intervention and a reference for reducing the incidence of clinical CI-AKI further.

Metformin Can Be Safely Used in Patients Exposed to Contrast Media: A Systematic Review and Meta-Analysis.

BACKGROUND: There have been few studies published on the use of contrast media (CM) in metformin-treated patients. In this study, we conducted a systematic review and meta-analysis to investigate the relationship between metformin and contrast-induced acute kidney injury (CI-AKI). METHODS: A comprehensive search of the Medline, PubMed, Embase, and Web of Science databases for literature on associations between metformin use and CI-AKI incidence was conducted. The pooled odds ratio (OR), or relative risk, as well as the corresponding 95% confidence intervals (CIs), was calculated to assess the relationship between metformin and CI-AKI risk as well as the incidence of lactic acidosis (LA). RESULTS: In total, seven studies met our eligibility criteria on associations between metformin use and CI-AKI incidence, comprising 2,325 individuals, with 279 new cases of CI-AKI exposed to CM. The pooled analysis revealed no statistically significant increase in the risk of CI-AKI development in patients who used metformin continuously (random-effects OR: 1.15, 95% CI: 0.70-1.90, p = 0.57). No cases of LA that occurred during CM exposure were reported. CONCLUSION: Metformin can be safely used in patients with moderate renal impairment (eGFR ≥ 30 mL/min/1.73 m2) during CM exposure.

Oral hydration as a safe prophylactic measure to prevent post-contrast acute kidney injury in oncologic patients with chronic kidney disease (IIIb) referred for contrast-enhanced computed tomography: subanalysis of the oncological group of the NICIR study.

BACKGROUND: T he objective of this study is to evaluate oral hydration compared to intravenous (i.v.) hydration in the prevention of post-contrast acute kidney injury (PC-AKI) in the oncologic subgroup of patients with stage IIIb chronic kidney disease (CKD) included in the NICIR study referred for elective contrast-enhanced computed tomography (CE-CT). MATERIAL AND METHODS: We performed a retrospective subanalysis of the oncological subgroup (174/228 patients, 74%) from a continuous prospective database of patients included in the recently published non-inferiority NICIR study. Patients received prophylaxis against PC-AKI with either oral hydration (500 mL of water 2 h before and 2000 mL during the 24 h after CE-CT) or i.v. hydration (sodium bicarbonate (166 mmol/L) 3 mL/kg/h starting 1 h before and 1 mL/kg/h during the first hour after CE-CT). The primary outcome was to compare the proportion of PC-AKI in the first 48 to 72 h after CE-CT in the two hydration groups. Secondary outcomes were to compare persistent PC-AKI, the need for haemodialysis, and the occurrence of adverse events related to prophylaxis in each group. RESULTS: Of 174 patients included in the subanalysis, 82 received oral hydration and 92 received i.v. hydration. There were no significant differences in clinical characteristics or risk factors between the two study arms. Overall the PC-AKI rate was 4.6% (8/174 patients), being 3.7% in the oral hydration arm (3/82 patients) and 5.4% (5/92 patients) in the i.v. hydration arm. The persistent PC-AKI rate was 1.2% (1/82 patients) in the oral hydration arm and 3.3% (3/92 patients) in the i.v. hydration arm. No patient required dialysis during the first month after CE-CT or had adverse effects related to the hydration regime. CONCLUSION: In oncological patients with stage IIIb CKD referred for elective CE-CT, the rate of PC-AKI in those receiving oral hydration did not significantly differ from that of patients receiving i.v. hydration.

The association between nutritional risk and contrast-induced acute kidney injury in patients undergoing coronary angiography: a cross-sectional study.

BACKGROUND: Nutritional risk is prevalent in various diseases, but its association with contrast-induced acute kidney injury (CI-AKI) remains unclear. This study aimed to explore this association in patients undergoing coronary angiography (CAG). METHODS: In this retrospective cross-sectional study, 4386 patients undergoing CAG were enrolled. Nutritional risks were estimated by nutritional risk screening 2002 (NRS-2002), controlling nutritional status (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), respectively. CI-AKI was determined by the elevation of serum creatinine (Scr). Multivariable logistic regression analyses and receiver operator characteristic (ROC) analyses were conducted. Subgroup analyses were performed according to age (< 70/≥70 years), gender (male/female), percutaneous coronary intervention (with/without), and estimated glomerular filtration rate (< 60/≥60 ml/min/1.73m2). RESULTS: Overall, 787 (17.9%) patients were diagnosed with CI-AKI. The median score of NRS-2002, CONUT, PNI, and GNRI was 1.0, 3.0, 45.8, and 98.6, respectively. Nutritional risk was proven to be associated with CI-AKI when four different nutritional tools were employed, including NRS-2002 ([3-7 vs. 0]: odds ratio [95% confidence interval], OR [95%CI] = 4.026 [2.732 to 5.932], P < 0.001), CONUT ([6-12 vs. 0-1]: OR [95%CI] = 2.230 [1.586 to 3.136], P < 0.001), PNI ([< 38 vs. ≥52]: OR [95%CI] = 2.349 [1.529 to 3.610], P < 0.001), and GNRI ([< 90 vs. ≥104]: OR [95%CI] = 1.822 [1.229 to 2.702], P = 0.003). This is consistent when subgroup analyses were performed. Furthermore, nutritional scores were proved to be accurate in predicting CI-AKI (area under ROC curve: NRS-2002, 0.625; CONUT, 0.609; PNI, 0.629; and GNRI, 0.603). CONCLUSIONS: Nutritional risks (high scores of NRS-2002 and CONUT; low scores of PNI and GNRI) were associated with CI-AKI in patients undergoing CAG.