Background/Aims: Contrast induced-acute kidney injury (CI-AKI) is one of the most common causes of acute kidney injury (AKI) in hospitalized patients. Mitophagy, the selective elimination of mitochondria via autophagy, is an important mechanism of mitochondrial quality control in physiological and pathological conditions. In this study, we aimed to determine effects of iohexol and iodixanol on mitochondrial reactive oxygen species (ROS), mitophagy and the potential role of mitophagy in CI-AKI cell models. Methods: Cell viability was measured by cell counting kit-8. Cell apoptosis, mitochondrial ROS and mitochondrial membrane potential were detected by western blot, MitoSOX fluorescence and TMRE staining respectively. Mitophagy was detected by the colocalization of LC3-FITC with MitoTracker Red, western blot and electronic microscope. Results: The results showed that mitophagy was induced in human renal tubular cells (HK-2 cells) under different concentrations of iodinated contrast media. Mitochondrial ROS displayed increased expression after the treatment. Rapamycin (Rap) enhanced mitophagy and alleviated contrast media induced HK-2 cells injury. In contrast, autophagy inhibitor 3-methyladenine (3-MA) down-regulated mitophagy and aggravated cells injury. Conclusions: Together, our finding indicates that iohexol and iodixanol contribute to the generation of mitochondrial ROS and mitophagy. The enhancement of mitophagy can effectively protect the kidney from iodinated contrast (iohexol)-induced renal tubular epithelial cells injury.
Recent progress in angiography and interventional therapy has revived interest in comparison of nephrotoxicity of low-or iso-osmolar contrast media, but detailed mechanisms and effective treatments of contrast-induced acute kidney injury (CI-AKI) remain elusive. We established a new model of CI-AKI and compared the nephrotoxicity of iohexol and iodixanol with a focus on renal oxidative stress, mitochondrial damage and mitophagy. Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats. Compared with iodixanol, iohexol induced a greater decrease in renal function, more severe morphological damage and mitochondrial ultrastructural changes, an increased number of apoptotic cells, decreased antioxidative enzymes with activation of NLRP3 inflammasome in renal tissue. Renal contrast media kinetics showed the immediate excretion of iohexol and the transient renal accumulation of iodixanol. Plasma mtDNA Tc numbers were positively correlated with markers of renal mitochondrial disruption but negatively correlated with the level of serum creatinine and the score of tubular injury. Of note, iodixanol appeared to induce a stronger activation of mitophagy than iohexol, evidenced by greater protein levels of LC3II and PINK1/Parkin in the renal tissue of iodixanol-treated rats. Taken together, our results indicate that iohexol induced more severe nephrotoxicity than iodixanol in vivo due to apoptosis, destruction of antioxidative defense machinery, activation of NLRP3 inflammasome, mitochondrial damage and mitophagy. Plasma mtDNA may serve as a biological marker for renal mitochondrial disruption and damage in CI-AKI. Antioxidative defense and mitophagy are involved in the process of CI-AKI and may be promising targets of therapies.
Contrast-induced acute kidney injury (CI-AKI) is a severe complication of intravascular applied radial contrast media, and recent progress in interventional therapy and angiography has revived interest in explaining detailed mechanisms and developing effective treatment. Recent studies have indicated a potential link between CI-AKI and microRNA (miRNA). However, the potential non-coding RNA-associated-competing endogenous RNA (ceRNA) pairs involved in CI-AKI still remain unclear. In this study, we systematically explored the circRNA or lncRNA-associated-ceRNA mechanism in a new rat model of CI-AKI through deep RNA sequencing. The results revealed that the expression of 38 circRNAs, 12 lncRNAs, 13 miRNAs and 127 mRNAs were significantly dysregulated. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses for mRNAs with significantly different expression and then constructed comprehensive circRNA or lncRNA-associated ceRNA networks in kidney of CI-AKI rats. Thereafter, two constructed ceRNA regulatory pathways in this CI-AKI rat model—novel_circ_0004153/rno-miR-144-3p/Gpnmb or Naglu and LNC_000343/rno-miR-1956-5p/KCP—were validated by real-time qPCR. This study is the first one to provide a systematic dissection of non-coding RNA-associated ceRNA profiling in kidney of CI-AKI rats. The selected non-coding RNA-associated ceRNA networks provide new insight for the underlying mechanism and may profoundly affect the diagnosis and therapy of CI-AKI.
Currently, little information is available to stratify the risks and predict acute kidney injury (AKI)-associated death. In this present cross-sectional study, a novel scoring model was established to predict the probability of death within 90 days in patients with AKI diagnosis. For establishment of predictive scoring model, clinical data of 1169 hospitalized patients with AKI were retrospectively collected, and 731 patients of them as the first group were analyzed by the method of multivariate logistic regression analysis to create a scoring model and further predict patient death. Then 438 patients of them as the second group were used for validating this prediction model according to the established scoring method. Our results showed that Patient’s age, AKI types, respiratory failure, central nervous system failure, hypotension, and acute tubular necrosis-individual severity index (ATN-ISI) score are independent risk factors for predicting the death of AKI patients in the created scoring model. Moreover, our scoring model could accurately predict cumulative AKI and mortality rate in the second group. In conclusion, this study identified the risk factors of 90-day mortality for hospitalized AKI patients and established a scoring model for predicting 90-day prognosis, which could help to interfere in advance for improving the quality of life and reduce mortality rate of AKI patients.
Background Contrast-induced acute kidney injury (CI-AKI) is a major adverse effect caused by intravascular administration of iodinated contrast medium. Whether there is a difference in CI-AKI incidence between iso-osmolar (IOCM) and low-osmolar contrast media (LOCM) among diabetic patients is controversial. Methods Randomized controlled trials comparing the nephrotoxic effects between IOCM and LOCM in diabetic patients with or without CKD (eGFR< 60 ml/min/1.73 m 2 ) were included in the analysis. The incidence of CI-AKI was defined as an initial increase in serum creatinine (SCr) concentration of at least 0.5 mg/dl or a rise in creatinine of 25% from baseline. Results A total of 2190 patients were included, among whom 1122 patients received IOCM and 1068 received LOCM. When compared to LOCM, IOCM had no significant benefit in preventing CI-AKI (OR = 1.66, [CI: 0.97–2.84], P = 0.06, I 2 = 54%). However, the difference between IOCM and LOCM was found when CI-AKI was defined as an absolute SCr increase (≥0.5 mg/dl) rather than a relative SCr increase (≥25%). Further analysis showed that LOCM resulted in more adverse events. Conclusions Whether there is a difference of CI-AKI incidence between IOCM and LOCM in diabetic patients was related to the selected diagnostic criteria. The incidence of adverse events was significantly lower with IOCM when compared with LOCM. Therefore, we suggest that IOCM may be used in diabetic and CKD (eGFR< 60 ml/min/1.73 m 2 ) patients. Electronic supplementary material The online version of this article (10.1186/s40644-019-0224-6) contains supplementary material, which is available to authorized users.
Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427–2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P1 = 0.930, P2 = 0.105; AUROC1 = 0.879 (95% CI 0.862–0.896), AUROC2 = 0.845 (95% CI 0.813–0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients.
A fully grouted cable bolt is normally loaded at rock joints by a combination of the axial and shear forces causing both axial extension and shear deformation of the cable. The proposed analyses presented here attempts to predict the joint shear strength and shear displacement. The analyses are based on the statically indeterminate beam theory and some basic findings and conclusions of other researchers. Parametrical investigation is performed on four influence factors including bolt pretension, joint friction angle, concrete strength and bolt installation angle. Although the true plastic moduli of the cable bolt deflecting section at failure are the essential parameters in this analysis, they are practically impossible to determine. Thus, the average cable moduli obtained from the cable tensile strength tests were used. The proposed analytical model was compared with the experimental results, showing a good agreement. This analytical work aims to develop a simple tool for the practicing geotechnical engineer to effectively evaluate the cable shear behaviour and the influence of fully grouted cable bolts on joint shear resistance. Cable bolting reinforcement is currently considered to be one of the best methods for 6 improving rock strata conditions and to control the strata movement and deformation. A fully 7 grouted cable bolt is normally loaded at rock joints by a combination of the axial and shear 8 forces causing both axial extension and shear deformation of the cable. The axial and shear 9 loads experienced by cable bolts are very complex as they are influenced by many factors, 10 such as cable strength, cable moduli, cable dimensions, rock strength, and joint properties. Disciplines Engineering | Science and Technology Studies
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