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.

Zero-contrast IVUS-guided complex PCI in a patient with NSTE-ACS and severe renal impairment.

A 76-year-old male with severe comorbidities and multiple cardiovascular risk factors including stage IV chronic kidney disease presents with non-ST-elevation myocardial infarction. An ultra-low contrast invasive coronary angiography using the DyeVert system and iso-osmolar contrast agent revealed a multivessel disease with heavy calcifications involving the left main stem and its bifurcation requiring a complex percutaneous coronary intervention. Because of the high risk of contrast-induced acute kidney injury, a zero-contrast intervention was performed using intravascular ultrasound guidance and dedicated stenting techniques with optimal imaging, clinical, and renal outcomes. Zero-contrast policies can be safely implemented even in complex clinical scenarios but at least two orthogonal angiographic projections should always be acquired to rule out distal complications.

Ox-LDL aggravates contrast-induced injury of renal tubular epithelial cells.

Hypercholesterolemia can aggravate contrast-induced acute kidney injury, and the exacerbation of renal tubular epithelial cell (RTEC) injury is a major cause. However, the exact mechanisms remain obscure. Mitophagy, a type of autophagy, selectively eliminates damaged mitochondria and reduces mitochondrial oxidative stress, which is strongly implicated in cell homeostasis and acute kidney injury. Oxidized low-density lipoprotein (Ox-LDL) is accumulated in hypercholesterolemia and has a cytotoxic effect. This study aimed to determine whether and how ox-LDL exacerbates contrast-induced injury in RTECs and to further explore whether PINK1/Parkin-dependent mitophagy is involved in this process. Iohexol and ox-LDL were used alone or in combination to treat HK-2 cells. Rapamycin pretreatment was utilized to enhance mitophagy. Cell viability, apoptosis, mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS) were detected by cell counting kit-8, TUNEL staining, JC-1 kit and MitoSOX fluorescence, respectively. The expression of mitophagy-related proteins (including PINK1, Parkin, and so on) and cleaved caspase-3 was confirmed by western blot. Colocalization of MitoTracker-labeled mitochondria and LysoTracker-labeled lysosomes was observed by fluorescence microscopy to evaluate mitophagy. The results of our study showed that ox-LDL aggravated MMP decline, mtROS release and apoptosis in iohexol-treated HK-2 cells, accompanied by a further increased autophagy level. Enhancement of PINK1/Parkin-dependent mitophagy by rapamycin alleviated apoptosis and mitochondrial injury in HK-2 cells in response to iohexol under ox-LDL condition. Therefore, our findings indicate that ox-LDL aggravates contrast-induced injury of RTECs by increasing mitochondrial damage and mitochondrial oxidative stress, which may be associated with the relative insufficiency of PINK1/Parkin-dependent mitophagy.

Quercetin improves contrast-induced acute kidney injury through the HIF-1α/lncRNA NEAT1/HMGB1 pathway.

CONTEXT: The risk of contrast-induced acute kidney injury (CI-AKI) is increasing and the harm is great. Quercetin is the main active component in Abelmoschus manihot (L.) Medik (Malvaceae) and was reported to reduce the expression of HIF-1α. OBJECTIVE: We investigate whether quercetin improves the CI-AKI through the HIF-1α/lncRNA NEAT1/HMGB1 pathway. MATERIALS AND METHODS: HK-2 cells were treated with iohexol (200 mg/mL) for 6 h to establish a CI-AKI model. Quercetin (20 µM) was administered to CI-AKI cells cultured in dishes for 24 h. Cell morphology was observed by a fluorescence microscope. MTT and TUNEL assays were used to detect cell survival rate and apoptosis. Relative mRNA levels were measured by qRT-PCR. Protein levels were detected using western blotting. IL-6 and TNF-α protein levels were tested by Elisa assay. Targeting binding sites of HIF-1α and lncRNA NEAT1 were detected by luciferase assay. RESULTS: The IC50 value of quercetin was 163.25 µM. The expression levels of HIF-1α, lncRNA NEAT1 and HMGB1 were upregulated in the CI-AKI cell model. Quercetin diminished cell injury and apoptosis via inhibiting HIF-1α. Silencing of HIF-1α targeting lncRNA MEAT1 diminished cell injury and apoptosis. Silencing lncRNA NEAT1 has the same effect via suppressing HMGB1 expression. Collectively, quercetin diminished cell injury and apoptosis in CI-AKI cell model via the inhibition of HIF-1α on lncRNA NEAT1/HMGB1 signalling pathway. DISCUSSION AND CONCLUSIONS: Quercetin diminished cell injury and apoptosis in CI-AKI cell mode via the inhibition of HIF-1α on the lncRNA NEAT1/HMGB1 signalling pathway, offering a potential novel therapeutic target for CI-AKI therapy.

Kidney Biomarkers of Injury and Repair as Predictors of Contrast-Associated AKI: A Substudy of the PRESERVE Trial.

RATIONALE & OBJECTIVE: The PRESERVE trial used a 2 × 2 factorial design to compare intravenous saline solution with intravenous sodium bicarbonate solution and oral N-acetylcysteine with placebo for the prevention of 90-day major adverse kidney events and death (MAKE-D) and contrast-associated acute kidney injury (CA-AKI) among patients with chronic kidney disease undergoing angiography. In this ancillary study, we evaluated the predictive capacities of preangiography injury and repair proteins in urine and plasma for MAKE-D, CA-AKI, and their impact on trial design. STUDY DESIGN: Longitudinal analysis. SETTING & PARTICIPANTS: A subset of participants from the PRESERVE trial. EXPOSURES: Injury (KIM-1, NGAL, and IL-18) and repair (MCP-1, UMOD, and YKL-40) proteins in urine and plasma 1 to 2 hours preangiography. OUTCOMES: MAKE-D and CA-AKI. ANALYTICAL APPROACH: We analyzed the associations of preangiography biomarkers with MAKE-D and with CA-AKI. We evaluated whether the biomarker levels could enrich the MAKE-D event rate and improve future clinical trial efficiency through an online biomarker prognostic enrichment tool available at prognosticenrichment.com. RESULTS: We measured plasma biomarkers in 916 participants and urine biomarkers in 797 participants. After adjusting for urinary albumin-creatinine ratio and baseline estimated glomerular filtration rate, preangiography levels of 4 plasma (KIM-1, NGAL, UMOD, and YKL-40) and 3 urine (NGAL, IL-18, and YKL-40) biomarkers were associated with MAKE-D. Only plasma KIM-1 level was significantly associated with CA-AKI after adjustment. Biomarker levels provided modest discriminatory capacity for MAKE-D. Screening patients using the 50th percentile of preangiography plasma KIM-1 or YKL-40 levels would have reduced the required sample size by 30% (∼2,000 participants). LIMITATIONS: Evaluation of prognostic enrichment does not account for changing trial costs, time needed to screen patients, or loss to follow-up. Most participants were male, limiting the generalizability of our findings. CONCLUSIONS: Preangiography levels of injury and repair biomarkers modestly predict the development of MAKE-D and can be used to improve the efficiency of future CA-AKI trials.

Application of diffusion tensor imaging and blood oxygenation level-dependent magnetic resonance imaging to assess bilateral renal function induced by Iohexol in rabbits.

BACKGROUND: Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) and diffusion tensor imaging (DTI) are useful methods for investigating the morphology and function of the kidneys, including revealing unilateral renal damage. Nevertheless, these techniques have not yet been applied for bilateral renal function. The aim of this study was to investigate whether the combination of DTI and BOLD could be used to examine different degrees of contrast-induced acute kidney injury (CI-AKI) in bilateral kidneys compared to standard methods such as serum creatinine (SCr) detection. METHODS: Forty-Two New Zealand white rabbits were divided into two groups: the experimental group and the control group. Physiological saline and iodine contrast agent (iohexol, 1.0 g iodine/kg, 1.0 ml/sec) were injected via the right renal artery. DTI and BOLD-MR data were acquired longitudinally at the baseline and 1, 24, 48, and 72 h after high-pressure syringe injection to measure the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative transverse relaxation rate (R2*). After the MR scan at each time point, three rabbits in each group were sacrificed, and changes in SCr and hypoxia-inducible factor-1α (HIF-1α) were analyzed using histopathology and immunochemistry. RESULTS: Twenty-four hours after iohexol administration, the values of ADC and FA decreased significantly (P < 0.05), while R2* values increased (P < 0.05) in the renal cortex (CO), outer medulla (OM) and inner medulla (IM). Besides, significant negative correlations were observed among ADC, FA, and R2* in CO, OM, and IM (all P < 0.001, r = - 0.654-0.828). CONCLUSIONS: DTI and BOLD can simultaneously and non-invasively assess different degrees of CI-AKI in bilateral kidneys.

Comparative Effectiveness of 12 Treatment Strategies for Preventing Contrast-Induced Acute Kidney Injury: A Systematic Review and Bayesian Network Meta-analysis.

BACKGROUND: To simultaneously evaluate the relative efficacy of multiple pharmacologic strategies for preventing contrast-induced acute kidney injury (AKI). STUDY DESIGN: Systematic review containing a Bayesian network meta-analysis of randomized controlled trials. SETTING & POPULATION: Participants undergoing diagnostic and/or interventional procedures with contrast media. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials comparing the active drug treatments with each other or with hydration alone. INTERVENTION: Any of the following drugs in combination with hydration: N-acetylcysteine (NAC), theophylline (aminophylline), fenoldopam, iloprost, alprostadil, prostaglandin E1, statins, statins plus NAC, bicarbonate sodium, bicarbonate sodium plus NAC, ascorbic acid (vitamin C), tocopherol (vitamin E), α-lipoic acid, atrial natriuretic peptide, B-type natriuretic peptide, and carperitide. OUTCOMES: The occurrence of contrast-induced AKI. RESULTS: The trial network included 150 trials with 31,631 participants and 4,182 contrast-induced AKI events assessing 12 different interventions. Compared to hydration, ORs (95% credible intervals) for contrast-induced AKI were 0.31 (0.14-0.60) for high-dose statin plus NAC, 0.37 (0.19-0.64) for high-dose statin alone, 0.37 (0.17-0.72) for prostaglandins, 0.48 (0.26-0.82) for theophylline, 0.62 (0.40-0.88) for bicarbonate sodium plus NAC, 0.67 (0.54-0.81) for NAC alone, 0.64 (0.41-0.95) for vitamins and analogues, 0.70 (0.29-1.37) for natriuretic peptides, 0.69 (0.31-1.37) for fenoldopam, 0.78 (0.59-1.01) for bicarbonate sodium, and 0.98 (0.41-2.07) for low-dose statin. High-dose statin plus NAC or high-dose statin alone were likely to be ranked the best or the second best for preventing contrast-induced AKI. The overall results were not materially changed in metaregressions or subgroup and sensitivity analyses. LIMITATIONS: Patient-level data were unavailable; unable to include some treatment agents; low event rates; imbalanced distribution of participants among treatment strategies. CONCLUSIONS: High-dose statins plus hydration with or without NAC might be the preferred treatment strategy to prevent contrast-induced AKI in patients undergoing diagnostic and/or interventional procedures requiring contrast media.

Selecting a strategy for prevention of contrast-induced nephropathy in clinical practice: an evaluation of different clinical practice guidelines using the AGREE tool.

BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is a potential complication of radio-contrast investigations. Many organisations have published guidance documents on the prevention of CI-AKI. Our aim is to explore the scope, content, consistency, practicality in clinical practice and reasons for eventual underlying discrepancies of these documents. METHODS: We searched the literature for guidance documents developed to guide prevention of CI-AKI up to 09/2014. Four reviewers appraised guideline quality using the 23-item AGREE-II instrument, which rates reporting of the guidance development process across six domains: scope and purpose, stakeholder involvement, rigour of development, clarity of presentation, applicability and editorial independence. Total scores were calculated as standardised averages by domain. RESULTS: Twenty-four guidance documents were evaluated. The guidance documents were produced by radiologists (N = 7), intensivists (N = 2), nephrologists (N = 6) or multidisciplinary teams (N = 9). One document did not mention the background of the authors. Only guidance documents (N = 15) that were not mere adaptations of existing guidelines were evaluated more in depth, using the AGREE tool. Overall, quality was mixed: only one clinical practice guidance document obtained an average score of >50% for all domains. The evidence was rated in a systematic way in only 11, and only 7 graded the strength of the recommendations. The Kidney Diseases Improving Global Outcomes guideline was the only one recommended without adaptions by all assessors. The guidance documents agreed in recommending pre-hydration as the main preventive measure, but there was difference in recommended total volumes, composition, rate and duration of the infused solutions. There was no consensus on the use of NaHCO3, with eight recommending it, six considering it and one not. Five guidance documents mentioned oral pre-hydration as a possibility, and none recommended N-acetylcysteine as solitary preventive measure. More recent guidance documents recommend avoiding hypertonic contrast media, but did not recommend preference of iso-osmolar over low-osmolar contrast media. Most guidance documents recognised pre-existing chronic kidney disease, diabetes, age and cardiovascular comorbidity as risk factors. CONCLUSIONS: There seems to be a relative consensus on the need for adequate pre-hydration to avoid CI-AKI, but recommendations to define at-risk populations for whom these measures should be applied and how they should be implemented differ substantially. Based on accumulating evidence, more recent guidelines do not recommend iso-osmolar over low-osmolar contrast media, whereas all recommend avoiding hypertonic agents.

Subclinical and clinical contrast-induced acute kidney injury: data from a novel blood marker for determining the risk of developing contrast-induced nephropathy (ENCINO), a prospective study.

OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL) is produced in response to tubular injury. Contrast-induced acute kidney injury (CI-AKI) is associated with adverse outcomes in chronic kidney disease (CKD) patients. We sought to characterize blood NGAL level and the degree of kidney injury in CKD patients who underwent coronary angiography. METHODS: This study was a prospective, blinded assessment of blood samples obtained from patients with estimated glomerular filtration rates (eGFRs) between 15 and 90 mL/min/1.73 m2 undergoing elective coronary angiography with iodinated contrast. Blood NGAL and serum creatinine were measured at baseline, 1, 2, 4, 6, 12, 24 and 48 h after contrast administration. RESULTS: A total of 63 subjects with a mean eGFR of 48.17±16.45 mL/min/1.73 m2 were enrolled. There was a graded increase in baseline NGAL levels across worsening stages of CKD (p=0.0001). Post-procedure NGAL increased from baseline in each stage of CKD. Eight (12.7%) patients were diagnosed with CI-AKI by diagnostic criteria of 2012 KDIGO definition of CI-AKI, and seven (11.1%) patients developed subclinical CI-AKI defined by a twofold or greater rise in NGAL. There was no relationship between baseline eGFR and diabetes on the composite outcome of subclinical and clinical CI-AKI. CONCLUSIONS: Baseline and post-procedure NGAL are progressively elevated according to the baseline stage of CKD. Using a twofold rise in NGAL, 46.7% of composite CI-AKI is detected and complements the 53.3% of cases identified using KDIGO criteria. Traditional risk predictors were not independently associated with this composite outcome.

Age-Related Effect of Uric Acid on Contrast-Induced Acute Kidney Injury of Patients Undergoing Coronary Angiography.

Background: The association between uric acid (UA) and contrast-induced acute kidney injury (CI-AKI) following coronary angiography (CAG) has been established. However, whether the association would vary with age remained undetermined. Methods: We performed the retrospective analysis based on the Cardio-renal Improvement II study, (ClinicalTrials.gov NCT05050877), which enrolled consecutive patients undergoing coronary angiography in 5 teaching hospitals in China from 2007 to 2020. The primary outcome was CI-AKI defined as the rise of serum creatinine (SCr) ≥ 0.5 mg/dL or 25% compared with the baseline value within 48 hours following CAG. The effect of age on the association between uric acid and CI-AKI was assessed by the logistic regression model. Results: A total of 36,550 patients (mean age 63.08±5.6-year-old, 41.7% men) were included in the study. After adjusting for the confounders, the risk of CI-AKI between each quartile of uric acid was insignificant in the young group. In patients of the middle group, lower UA was associated with a lower risk of CI-AKI while higher UA was associated with a higher risk (Q1 OR: 0.853, 95% CI: 0.734-0.993; Q4 OR: 1.797, 95% CI: 1.547-2.09). In patients of the elder group, lower and higher UA were both associated with a higher risk of CI-AKI (Q1 OR: 1.247, 95% CI: 1.003-1.553; Q4 OR: 1.688, 95% CI: 1.344-2.124). The restricted cubic spline indicated a non-linear association between UA and CI-AKI in middle and elder age groups but a linear association in the young age group. Conclusion: The association between uric acid and CI-AKI vary in patients of different age. Patients with elder age should maintain a middle level of uric acid while patients with middle age should consider a lower level of uric acid to reduce the risk of CI-AKI. The level of UA was an insignificant risk factor for CI-AKI in young patients.

NGAL as Biomarker of Clinical and Subclinical Damage of Kidney Function after Coronary Angiography.

Contrast-induced acute kidney injury (CI-AKI) is a serious complication after angiographic examinations in cardiology. Diagnosis may be delayed based on standard serum creatinine, and subclinical forms of kidney damage may not be detected at all. In our study, we investigate the clinical use in these directions of a "damage"-type biomarker-neutrophil gelatinase-associated lipocalin (NGAL). Among patients with a high-risk profile undergoing scheduled coronary angiography and/or angioplasty, plasma NGAL was determined at baseline and at 4th and 24th h after contrast administration. In the CI-AKI group, NGAL increased significantly at the 4th hour (Me 109.3 (IQR 92.1-148.7) ng/mL versus 97.6 (IQR 69.4-127.0) ng/mL, p = 0.006) and at the 24th hour (Me 131.0 (IQR 81.1-240.8) ng/mL, p = 0.008). In patients with subclinical CI-AKI, NGAL also increased significantly at the 4th hour (Me 94.0 (IQR 75.5-148.2) ng/mL, p = 0.002) and reached levels close to those in patients with CI-AKI. Unlike the new biomarker, however, serum creatinine did not change significantly in this group. The diagnostic power of NGAL is extremely good-AUC 0.847 (95% CI: 0.677-1.000; p = 0.001) in CI-AKI and AUC 0.731 (95% CI: 0.539-0.924; p = 0.024) in subclinical CI-AKI. NGAL may be a reliable biomarker for the early diagnosis of clinical and subclinical forms of renal injury after contrast angiographic studies.

The role of urinary Dickkopf-3 in the prediction of acute kidney injury: a systematic review meta-analysis.

BACKGROUND: To systematically evaluate the diagnostic efficacy of urinary Dickkopf-Related Protein 3 (DKK-3) in acute kidney injury and to explore the clinical application value of urinary DKK-3. METHOD: English databases (PubMed, Embase, Cochrane, and WOS) and Chinese databases (VIP, WanFang data, and China National Knowledge Internet) were screened for relevant papers published before March 12, 2023. After literature screening and data extraction, quality assessment was performed according to the QUADAS-2 scoring system. Then, the combined diagnostic and predictive parameters were calculated using a bivariate mixed effect meta-analysis model. Deek's funnel plot asymmetry test assessed publication bias, and Fagan's nomogram plot was used to verify its clinical utility. RESULT: A total of 5 studies involving 2787 patients were included in this meta-analysis, of which 4 focused on contrast-induced acute kidney injury (CI-AKI) and 1 focused on AKI associated with cardiac surgery. The analysis showed that urine Dickkopf-3 has high diagnostic accuracy for AKI, with a sensitivity of 0.55 (95% CI [0.41, 0.68]), specificity of 0.80 (95% CI [0.70, 0.87]), positive likelihood ratio (PLR) of 2.7 [1.8, 4.1], negative likelihood ratio (NLR) of 0.56 [0.42, 0.75], diagnostic odds ratio (DOR) of 5 [3, 9], and AUC of 0.74 [0.70-0.77]. We did not perform subgroup analyses for predictive value due to the small number of included studies. CONCLUSION: Urinary DKK3 may have limited predictive ability for acute kidney injury, especially for AKI associated with cardiac surgery. Therefore, urinary DKK3 may serve as a potential predictor for AKI. However, clinical studies with larger samples are still needed for validation.

Repeated Dose of Contrast Media and the Risk of Contrast-Induced Acute Kidney Injury in a Broad Population of Patients Hospitalized in Cardiology Department.

Contrast-induced acute kidney injury (CI-AKI) can lead to the development of chronic kidney disease (CKD) and impaired in-hospital and long-term outcomes among cardiac patients. The aim of this study was to evaluate the impact of repeated contrast media (CM) administration during a single hospitalization on the rate of CI-AKI. The study group (n = 138) comprised patients with different diagnoses who received CM more than once during hospitalization, while the control group (n = 153) involved CAD patients subject to a single CM dose. Following propensity score matching (PSM), both groups of n = 84 were evenly matched in terms of major baseline variables. CI-AKI was defined by an absolute increase in SCr ≥ 0.3 mg/dL or >50% relative to the baseline value within 48-72 h from the last CM dose. Patients in the study group were older, had a higher prevalence of diabetes and CKD, received a higher total volume of CM, had a lower left ventricular ejection fraction, lower prevalence of multivessel coronary artery disease (MV-CAD), and a trend towards a lower prevalence of arterial hypertension and smoking. SCr did not differ between the study and control groups at 72 h after the CM use. CI-AKI occurred in 18 patients in the study (13.0%) and in 18 patients (11.8%) in the control group (p = 0.741). The rate of CI-AKI was also comparable following the PSM (13.1% vs. 13.1%, p = 1.0). Logistic regression analysis revealed that CKD, diabetes mellitus, MV-CAD, age, and non-steroidal anti-inflammatory drugs use, but not repeated CM use, were independent predictors of CI-AKI.

Shortage of iodinated contrast media: Status and possible chances - A systematic review.

PURPOSE: Covid-19 related lockdowns have resulted in a shortage of iodinated contrast media (ICM) in 2022. Health care providers have reacted with implementing conservation strategies to stay operational without compromising patient care. Although articles describing the implemented Interventions have been published, possible chances of the shortage have not yet been mentioned in the literature. METHODS: We conducted a literature search in PubMed and Google Scholar, and analysed the background, interventions, and possible benefits of low-dose ICM regimens. RESULTS: We included 22 articles dealing with "ICM shortage" for the analysis. The delivery bottlenecks in the USA and Australia led to two different countermeasures, 1. reduction of the number of contrast-enhanced image-guided examinations and 2. reduction of the (single) ICM dose. Interventions from both groups have resulted in significant reduction of ICM usage; however, group 1 has contributed more to overall ICM reduction. As benefit of the ICM reduction, we revealed an increased safety for patients at risk (e.g. hypersensitivity reactions, contrast-induced acute kidney injury, thyroid toxic effects). CONCLUSION: The ICM shortage of 2022 has forced health care providers to implement conservation strategies to stay operational. Although there were already proposals for dose reduction before the corona pandemic and the associated supply bottlenecks, this situation led to the use of a reduced amount of contrast agent on a large scale. This presents a good opportunity to reconsider protocols and the use of contrast-enhanced imaging in general for future practice as it offers chances and advantages regarding costs, environmental impact, and patient safety.

Low-Osmolar vs. Iso-Osmolar Contrast Media on the Risk of Contrast-Induced Acute Kidney Injury: A Propensity Score Matched Study.

Objective: Among the various risk factors associated with contrast-induced acute kidney injury (CI-AKI), the importance of osmolality and viscosity is emerging among the characteristics of contrast media (CM) itself. High osmolality CM (HOCM) is deprecated and low osmotic pressure (LOCM) and iso-osmotic pressure (IOCM) are mainly used in clinical situations where the results of studies on their effect on the development of CI-AKI are contradictory. We evaluated the association between the type of CM and the risk of CI-AKI. Materials and Methods: A retrospective observational cohort study to analyze the effect of the type of CM on the development of CI-AKI. Using propensity score (PS) matching, 2,263 LOCM and IOCM groups were paired for analysis from 5,267 patients and fulfilled the inclusion criteria among 12,742 patients who underwent CAG between 1 January 2007, and 31 December 2016. LOCM included iopromide and iopamidol, IOCM was iodixanol. CI-AKI, which was the primary endpoint, was defined based on the Kidney Disease Improving Global Outcomes criteria within 48 h after exposure to the CM. A multivariable logistic regression analysis was used in the unmatched and matched cohorts, respectively. In addition, a stratified model on clinically important variables, including a high Mehran score (≥ 6), was also used in the matched cohort. Results: LOCM users showed an increased incidence of CI-AKI (11.7% vs. 9.3%; p = 0.006), but it lost statistical significance after PS matching (9.9% vs. 9.5%, p = 0.725). In multivariable analyses, the adjusted odds ratio for CI-AKI in the LOCM group were 1.059 [95% confidence interval (CI) = 0.875-1.282; p = 0.555] in unmatched cohort and 0.987 (95% CI = 0.803-1.214; p = 0.901) in matched cohort. These results were also consistent with the high-risk (high Mehran score) group. Conclusions: Although the role of CM types in the development of CI-AKI has been debated, our observation shows that the selection between LOCM and IOCM during CAG has no influence on the incidence of CI-AKI.

Anemia is associated with increased risk of contrast­induced acute kidney injury: A Systematic Review and Meta-analysis.

Previous studies have identified numerous risk factors of contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary angiography. However, the association between anemia and CI-AKI remains conflicting. Thus, we conducted a meta-analysis to further clarify the relationship between anemia and CI-AKI. PubMed, EMBASE and Web of Science were systematically searched from inception to June 2020 to identify eligible studies. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the correlation between anemia and CI-AKI. The potential publication bias was estimated using funnel plot and Begg's test. A total of 13 studies (five case-control studies and eight cohort studies) comprising 27,135 patients were included. The pooled results showed that anemia was a significant risk factor of CI-AKI (OR, 1.82; 95% CI, 1.27-2.61). Moreover, the results of subgroup analyses and sensitivity analyses were basically consistent with the overall pooled result. Funnel plot and Begg's test indicated that there existed potential publication bias, but the result of trim and filled analysis showed that the pooled results kept stable after adding 'missing' studies. This meta-analysis suggested that anemia may be correlated with an increased incidence of CI-AKI in patients undergoing coronary angiography. However, our conclusions should be interpreted with caution due to some limitations. Therefore, further high-quality trials should be conducted to confirm our findings.

Corrigendum: A Novel Antioxidant Protects Against Contrast Medium-Induced Acute Kidney Injury in Rats.

[This corrects the article DOI: 10.3389/fphar.2020.599577.].

The Application of Functional Magnetic Resonance Imaging in Type 2 Diabetes Rats With Contrast-Induced Acute Kidney Injury and the Associated Innate Immune Response.

AIMS: Contrast-induced acute kidney injury (CI-AKI) is the third most common in-hospital acquired AKI, and its mechanism is not fully clear. Its morbidity increases among populations with chronic kidney disease (CKD), older age, diabetes mellitus (DM), and so on. Immediate and effective noninvasive diagnostic methods are lacking, so CI-AKI often prolongs hospital stays and increases extra medical costs. This study aims to explore the possibility of diagnosing CI-AKI with functional magnetic resonance imaging (fMRI) based on type 2 DM rats. Moreover, we attempt to reveal the immune response in CI-AKI and to clarify why DM is a predisposing factor for CI-AKI. METHODS: A type 2 DM rat model was established by feeding a high-fat and high-sugar diet combined with streptozotocin (STZ) injection. Iodixanol-320 was the contrast medium (CM) administered to rats. Images were obtained with a SIEMENS Skyra 3.0-T magnetic resonance imager. Renal histopathology was evaluated using H&E staining and immunohistochemistry (IHC). The innate immune response was revealed through western blotting and flow cytometry. RESULTS: Blood oxygenation level-dependent (BOLD) imaging and intravoxel incoherent motion (IVIM) imaging can be used to predict and diagnose CI-AKI effectively. The R 2 ∗ value (r > 0.6, P < 0.0001) and D value (| r| > 0.5, P < 0.0001) are strongly correlated with histopathological scores. The NOD-like receptor pyrin 3 (NLRP3) inflammasome participates in CI-AKI and exacerbates CI-AKI in DM rats. Moreover, the percentages of neutrophils and M1 macrophages increase dramatically in rat kidneys after CM injection (neutrophils range from 56.3 to 56.6% and M1 macrophages from 48 to 54.1% in normal rats, whereas neutrophils range from 85.5 to 92.4% and M1 macrophages from 82.1 to 89.8% in DM rats). CONCLUSIONS/INTERPRETATION: BOLD and IVIM-D can be effective noninvasive tools in predicting CI-AKI. The innate immune response is activated during the progression of CI-AKI and DM will exacerbate this progression.

Dickkopf-3 in the prediction of contrast media induced acute kidney injury.

BACKGROUND: Dickkopf-3 (DKK3) has recently been discovered as a urinary biomarker for the prediction of acute kidney injury (AKI) after cardiac surgery. This finding needs to be confirmed for AKI in other clinical settings. The present study investigates whether DKK3 can predict contrast-induced AKI (CI-AKI). METHODS: We performed a prospective study in 490 patients undergoing coronary angiography. Primary endpoint was an increase in serum creatinine concentration ≥ 0.3 mg/dl within 72 h after the procedure. DKK3 was assessed < 24 h before coronary angiography. Predictive accuracy was assessed by receiver operating characteristic (ROC) curves. RESULTS: CI-AKI was observed in 30 (6.1%) patients, of whom 27 corresponded to stage I and 3 to stage II according to the Acute Kidney Injury Network (AKIN) criteria. Subjects who developed CI-AKI had a 3.8-fold higher urinary DKK3/creatinine ratio than those without CI-AKI (7.5 pg/mg [interquartile range [IQR] 1.2-1392.0] vs. 2.0 pg/mg [IQR 0.9-174.0]; p = 0.047). ROC analysis revealed an area under the curve (AUC) of 0.61. Among subjects without clinically overt chronic kidney disease (estimated glomerular filtration rate [eGFR] > 60 ml/min, urinary albumin creatinine ratio < 30 mg/g), the DKK3/creatinine ratio was 5.4-fold higher in those with subsequent CI-AKI (7.5 pg/mg [IQR 0.9-590.1] vs. 1.38 pg/mg [IQR 0.8-51.0]; p = 0.007; AUC 0.62). Coronary angiography was associated with a 43 times increase in the urinary DKK3/creatinine ratio. CONCLUSIONS: Urinary DKK3 is an independent predictor of CI-AKI even in the absence of overt chronic kidney disease (CKD). The study thereby expands the findings on DKK3 in the prediction of postoperative loss of kidney function to other entities of AKI.