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3.
Am J Cardiol ; 211: 209-218, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37984642

RESUMO

To investigate the long-term effects of 2 commonly used low-osmolar contrast media, iohexol and iopromide, on renal function and survival in patients who underwent coronary angiography. A total of 14,141 cardiology patients from 2006 to 2013 were recruited, of whom 1,793 patients (679 patients on iohexol and 1,114 on iopromide) were evaluated for long-term renal impairment and 5,410 patients (1,679 patients on iohexol and 3,731 on iopromide) were admitted for survival analyses spanning as long as 15 years. Univariate and multivariate logistic regression were used to explore the risk factors for long-term renal impairment. Cox proportional hazard regression was used to investigate the risk factors affecting survival. Propensity score matching and inverse probability of treatment weighting were applied to balance the baseline clinical characteristics. Patients receiving iohexol demonstrated a greater occurrence of renal impairment compared with those who received iopromide. Such difference remained consistent both before and after propensity score matching or inverse probability of treatment weighting, with a statistical significance of p <0.05. Among clinical variables, receiving contrast-enhanced contrast tomography/magnetic resonance imaging during follow-up, antihypertensive medication usage, presence of proteinuria, and anemia were identified as risk factors for long-term renal impairment (p = 0.041, 0.049, 0.006, and 0.029, respectively). During survival analyses, the difference was insignificant after propensity score matching and inverse probability of treatment weighting. In conclusion, administration of iohexol was more likely to induce long-term renal impairment than iopromide, particularly among patients diagnosed with anemia and proteinuria and those taking antihypertensive medication and with additional contrast exposure. The all-cause mortality, however, showed no significant difference between iohexol and iopromide administration.


Assuntos
Anemia , Insuficiência Renal , Humanos , Iohexol/efeitos adversos , Angiografia Coronária/efeitos adversos , Angiografia Coronária/métodos , Meios de Contraste/efeitos adversos , Anti-Hipertensivos , Insuficiência Renal/induzido quimicamente , Insuficiência Renal/epidemiologia , Proteinúria/induzido quimicamente , Ácidos Tri-Iodobenzoicos/efeitos adversos
4.
Mayo Clin Proc ; 98(12): 1820-1830, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38043998

RESUMO

OBJECTIVE: To assess the effects of patient variables, examination variables, and seasonality on allergic-like and physiologic reactions to iodinated contrast material (ICM). PATIENTS AND METHODS: All ICM-enhanced computed tomography (CT) examinations performed from June 1, 2009, to May 9, 2017, at our institution were included. Reactions were identified and categorized as allergic-like or physiologic and mild, moderate, or severe. The effect of patient and examination variables on reactions was evaluated by logistic regression models. RESULTS: A total of 359,977 CT examinations performed on 176,886 unique patients were included. A total of 1150 allergic-like reactions (0.32%; 19 severe [0.005%]) and 679 physiologic reactions (0.19%; 3 severe [0.0008%]) occurred. On multivariable analysis, iopromide had higher rates of reactions compared with iohexol (allergic-like reactions: odds ratio [OR], 3.07 [95% CI, 2.37 to 3.98], P<.0001; physiologic reactions: OR, 2.60 [1.92 to 3.52], P<.0001). Non-White patients had higher rates of reactions compared with White patients (allergic-like reactions: OR, 1.77 [1.36-2.30], P<.0001; physiologic reactions: OR, 1.76 [1.27-2.42], P=.0006). Patient age, sex, prior ICM reaction, ICM dose, CT location, and CT type were also significantly associated with reactions. No significant seasonality trend was observed (P=.07 and .80). CONCLUSION: Non-White patients and patients administered iopromide had higher rates of acute reactions compared with White patients and patients administered iohexol. Younger patients (<50 years vs 51 to 60 years), female sex, history of ICM allergy or other allergies, ICM dose, and contrast-enhanced CT location and type also correlated with higher acute reaction rates.


Assuntos
Meios de Contraste , Hipersensibilidade a Drogas , Humanos , Feminino , Meios de Contraste/efeitos adversos , Iohexol/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/etiologia
5.
Redox Biol ; 67: 102929, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37856999

RESUMO

Contrast-induced acute kidney injury(CI-AKI) is the third cause of AKI. Although tubular injury has been regarded as an important pathophysiology of CI-AKI, the underlying mechanism remains elusive. Here, we found arginase2(ARG2) accumulated in the tubules of CI-AKI mice, and was upregulated in iohexol treated kidney tubular cells and in blood samples of CI-AKI mice and patients, accompanied by increased nitrosative stress and apoptosis. However, all of the above were reversed in ARG2 knockout mice, as evidenced by the ameliorated kidney dysfunction and the tubular injury, and decreased nitrosative stress and apoptosis. Mechanistically, HO-1 upregulation could alleviate iohexol or ARG2 overexpression mediated nitrosative stress. Silencing and overexpressing ARG2 was able to upregulate and downregulate HO-1 expression, respectively, while HO-1 siRNA had no effect on ARG2 expression, indicating that ARG2 might inhibit HO-1 expression at the transcriptional level, which facilitated nitrosative stress during CI-AKI. Additionally, CREB1, a transcription factor, bound to the promoter region of ARG2 and stimulated its transcription. Similar findings were yielded in cisplatin- or vancomycin-induced AKI models. Taken together, ARG2 is a crucial target of CI-AKI, and activating CREB1/ARG2/HO-1 axis can mediate tubular injury by promoting nitrosative stress, highlighting potential therapeutic strategy for treating CI-AKI.


Assuntos
Injúria Renal Aguda , Iohexol , Humanos , Camundongos , Animais , Iohexol/efeitos adversos , Iohexol/metabolismo , Estresse Nitrosativo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/genética , Injúria Renal Aguda/tratamento farmacológico , Rim/metabolismo , Fatores de Transcrição/metabolismo , Cisplatino/farmacologia , Apoptose , Camundongos Endogâmicos C57BL
6.
Eur J Med Res ; 28(1): 458, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37880738

RESUMO

OBJECTIVE: To identify the risk factors for moderate and severe contrast media extravasation and provide effective guidance to reduce the degree of extravasation injuries. METHODS: We observed 224 adult patients who underwent contrast media extravasation at Xiangya Hospital of Central South University, Hunan Provincial Maternal and Child Healthcare Hospital, and Xiangya Changde Hospital, Hunan Province between January 1, 2018 and December 31, 2022. Risk factors for moderate extravasation injuries were evaluated using univariate and multivariate logistic regression. RESULTS: Among 224 patients, 0 (0%) had severe, 18 (8.0%) had moderate, and 206 (92.0%) had mild contrast media extravasation injury. Multivariate logistic regression analysis revealed malignant tumors (odds ratio [OR] = 6.992, 95% confidence interval [CI]: 1.674-29.208), Iohexol (OR = 9.343, 95% CI 1.280-68.214), large-volume (> 50 mL) extravasation (OR = 5.773, 95% CI 1.350‒24.695), and injection site (back of the hand) (OR = 13.491, 95% CI 3.056-59.560) as independent risk factors for moderate injury. CONCLUSION: Risk factors for moderate contrast media extravasation injury are malignant tumors, iohexol, large-volume (> 50 mL) extravasation, and back-of-the-hand injection. Analysis of these risk factors can help reduce the degree of injury after extravasation. CLINICAL RELEVANCE STATEMENT: High-risk patients with extravasation support should choose the appropriate contrast media type, avoiding back-of-the-hand injections. We recommend that patients with cancer be implanted with a high-pressure resistant central venous catheter and receive effective measures to timely detect and reduce extravasation.


Assuntos
Extravasamento de Materiais Terapêuticos e Diagnósticos , Neoplasias , Adulto , Humanos , Meios de Contraste/efeitos adversos , Extravasamento de Materiais Terapêuticos e Diagnósticos/etiologia , Iohexol/efeitos adversos , Estudos Prospectivos , Tomografia Computadorizada por Raios X
7.
Pan Afr Med J ; 45: 144, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808435

RESUMO

Introduction: vascular opacification using iodinated contrast media (ICM) is often the primary diagnostic and therapeutic approach. However, the risk of post-injection nephrotoxicity of ICM is significantly higher in patients with underlying nephropathy. This study aimed to determine the incidence of Contrast Media Induced Nephropathy (CMIN) and identify predictive factors for its occurrence in patients from a cardiology department. Methods: our prospective study involved 158 patients who underwent coronary angiography or angioplasty at the cardiology department between December 2017 and May 2018. Two types of ICM were used in our study: Iopromide and Iohexol. All patients received either physiological serum (9‰) or bicarbonate serum (14‰) intravenously for hydration. We defined impaired renal function as an increase in creatinine ranging from 10 to 26 µmol/L, while CMIN was defined as an increase in serum creatinine exceeding 26.5 µmol/L. We investigated the factors associated with CMIN using logistic regression analysis. Results: the mean age of our patients was 60 ± 11 years (range: 29-82), with a predominance of men 63.9% (n=101). The most common cardiovascular risk factors were tobacco (36.1%, n = 57), diabetes (48.1%, n =76), hypertension (55%, n = 87). Pre-procedural creatinine averaged 81.1 ± 47.3 µmol / L with extremes ranging from 39 to 600 µmol / L. The median Mehran risk score was 3.2 (range: 0- 15). The interventional cardiology act consisted of coronary angiography in 86.2% (n=136) of cases, coronary angioplasty in 2.5% (n=4) of cases. We used iohexol and iopromide in 57.6% (n=91) and 42.4% (n=67) of cases, respectively. The overall incidence of CMIN was 9.5% (n=9). The multivariable regression analysis identified 4 risk factors independently linked to the occurrence of CMIN which were Pre-existing renal failure (OR: 6.05, 95%CI [1.23-29.62], p = 0.026), anemia (OR: 0.043, CI [1.03-8.96], p = 0.043), the toxic dose of PC (OR: 4.7, CI [1.28-17.7], p=0.02), and at a Mehran score = 11 (OR: 3.7, CI [0.88-15.6], p=0.036). Conclusion: the most effective approach for CMIN is prevention, which focuses on addressing modifiable risk factors to minimize the risk especially in patients with pre-existing renal failure.


Assuntos
Angioplastia Coronária com Balão , Nefropatias , Insuficiência Renal , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Feminino , Meios de Contraste/efeitos adversos , Iohexol/efeitos adversos , Creatinina , Estudos de Casos e Controles , Estudos Prospectivos , Tunísia/epidemiologia , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Angiografia Coronária/efeitos adversos , Insuficiência Renal/etiologia , Fatores de Risco
8.
Pain Physician ; 26(4): 369-373, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37535776

RESUMO

BACKGROUND: There is a global shortage of iohexol contrast media, commonly used in epidural injections, as a result of lockdown and decreased production due to COVID-19. Iohexol bottles are designated for single use, which, depending on the vials available, often leads to wasting up to 95% of this limited resource. However, avoiding multiple withdrawals may be unnecessary if withdrawing multiple times using sterile technique does not increase the risk for contamination. OBJECTIVES: The purpose of our study is to determine whether multiple withdrawals from iohexol injection bottles using a sterile technique poses a greater risk of introducing contaminants than a single withdrawal. Furthermore, we wish to determine the extent to which bacteria can survive and grow in the contrast media. STUDY DESIGN: Experimental. SETTING: Outpatient fluoroscopic suite and laboratory. METHODS: Twenty-one 100 mL 300 mg(iodine)/mL iohexol injection bottles, after one clinical use, were tested after the first and last withdrawals (withdrawal one and withdrawal 9 or 10) for bacterial and fungal specimens using culture media and 3M™ Petrifilms™. To determine the ability of methicillin-susceptible Staphylococcus aureus (MSSA) to survive or grow in the media, MSSA was added to different concentrations (0, 25, 50, 75, and 100%) of iohexol contrast media. RESULTS: There was no growth observed in cultures or on Petrifilms among the first and last draws of any of the samples. When bacteria were grown in different dilutions of the media, there was a significant, approximately one log decrease in counts from 0% contrast media to 100% contrast media (8.4 x 108 vs 5.6 x 107, P < 0.01). LIMITATIONS: Our study is limited in the number of samples tested and would benefit from additional investigation before consideration of clinical application. CONCLUSIONS: Our results suggest that single-use 300 iohexol bottles may be reusable and that the contrast media is mildly antimicrobial, but not enough to retard contamination. In setting of shortages, contrast media bottles can safely be reused. This is valuable for conserving resources and limiting unnecessary health care-associated costs.


Assuntos
COVID-19 , Iohexol , Humanos , Iohexol/efeitos adversos , Meios de Contraste/efeitos adversos , Controle de Doenças Transmissíveis
9.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446141

RESUMO

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-ß1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.


Assuntos
Injúria Renal Aguda , Iohexol , Humanos , Iohexol/efeitos adversos , Meios de Contraste/efeitos adversos , Apoptose , Injúria Renal Aguda/induzido quimicamente , Ciclo Celular , Fibrose
10.
J Biochem Mol Toxicol ; 37(8): e23379, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37186061

RESUMO

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.


Assuntos
Injúria Renal Aguda , Hipercolesterolemia , Humanos , Iohexol/efeitos adversos , Iohexol/metabolismo , Lipoproteínas LDL/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Células Epiteliais/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteínas Quinases/metabolismo , Sirolimo/efeitos adversos , Sirolimo/metabolismo
11.
J Comput Assist Tomogr ; 47(4): 608-612, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36944108

RESUMO

OBJECTIVE: To investigate the incidence of severe iodinated contrast media (ICM)-related hypersensitivity reaction (HSR) and to find the optimal alternative ICM to reduce the risk of severe HSR recurrence. METHODS: We retrospectively reviewed 23,383,183 cases of ICM administration between January 2015 and December 2019 from the nationwide health insurance database. We classified ICMs based on generic profiles and the presence of N-(2,3-dihydroxypropyl) carbamoyl side chains. The incidence of severe and recurrent severe HSRs was calculated, and χ2 tests were performed to compare the prevalence of severe HSR according to ICM groups. In addition, logistic regression analyses were used to assess differences between ICM groups. RESULTS: The incidence of severe HSRs was 1.92% (450,067 of 23,282,183). Among 1,875,245 individuals who received ICM twice on different days, severe HSR occurred in 40,850 individuals, and severe HSR recurred in 3319 individuals (8.12%). The risk of recurrence significantly decreased when the ICM changed (9.24% vs 7.08%, P < 0.001), especially when the ICM changed to one with a different side chain (6.74%, P < 0.001). In addition, compared with the reuse of the culprit agent, using combinations of iobitridol/iohexol (odds ratio [OR], 0.696; P = 0.04), iohexol/iopamidol (OR, 0.757; P = 0.007), iopamidol/iohexol (OR, 0.447; P < 0.001), and ioversol/iohexol (OR, 0.683; P = 0.04) reduced the risk of recurrence of severe HSR. CONCLUSIONS: Changing the culprit ICM to that with a different side chain can reduce severe HSR recurrence. The optimal choice of an alternative ICM depends on the causative agent.


Assuntos
Hipersensibilidade a Drogas , Compostos de Iodo , Humanos , Meios de Contraste/efeitos adversos , Iohexol/efeitos adversos , Iopamidol/efeitos adversos , Hipersensibilidade a Drogas/epidemiologia , Hipersensibilidade a Drogas/prevenção & controle , Hipersensibilidade a Drogas/etiologia , Estudos Retrospectivos
12.
J Biochem Mol Toxicol ; 37(1): e23238, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36207783

RESUMO

Contrast-induced nephropathy (CIN) is an acute kidney injury (AKI) observed after the administration of contrast media. Calcium channel blockers (CCBs) have been reported to exert a renal protective effect. This study aims to investigate the role of cilnidipine, a novel CCBs, on CIN by regulating the calcium/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)/mitochondrial permeability transition pore (mPTP) pathway. Here, iohexol, a representative contrast media, was used to establish CIN model. KN-93 (CaMKⅡ inhibitor) and atractyloside (mPTP opener) were administered in rats, and CaMKⅡ overexpression was used in Human proximal tubular epithelial cells. Markers of renal injury (serum creatinine, blood urea nitrogen, and urinary NAGL), hematoxylin-eosin stain, oxidative stress (ROS, superoxide dismutase [SOD], and malondialdehyde [MDA] levels), cell death (MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling [TUNEL]), mitochondrial function (mPTP, mitochondrial membrane potential [MMP], and ATP) were assessed. Western blots were used to measure the expression levels of Bax/Bcl-2, caspase-3, CaMKⅡ/mPTP signaling pathways. Results showed that cilnidipine markedly improved kidney function, and alleviated tubular cell apoptosis, oxidative stress and mitochondrial damage induced by iohexol in vitro and in vivo. The underlying mechanism may be that cilnidipine relieved CaMKⅡ activation and mPTP opening induced by iohexol. All of these protective effects of cilnidipine were attenuated by CaMKⅡ overexpression and atractyloside (mPTP opener) pretreatment. Moreover, KN-93 (CaMKⅡ inhibitor) treatment showed a similar renal protective effect with cilnidipine, while the protective effect of cilnidipine on kidney in CIN rats was not further suppressed by KN-93 cotreatment. These in vitro and in vivo results point toward the fact that cilnidipine might be a novel therapeutic drug against contrast-induced nephrotoxicity in a CaMKⅡ-dependent manner.


Assuntos
Injúria Renal Aguda , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Humanos , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/uso terapêutico , Iohexol/efeitos adversos , Meios de Contraste/efeitos adversos , Atractilosídeo/efeitos adversos , Apoptose , Estresse Oxidativo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/tratamento farmacológico
13.
Dis Markers ; 2022: 4158692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225198

RESUMO

Background: This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods: The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results: The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion: Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.


Assuntos
Injúria Renal Aguda , Rosiglitazona , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Caspase 3/metabolismo , Creatinina/metabolismo , Furosemida/efeitos adversos , Interleucina-10/genética , Interleucina-10/metabolismo , Iohexol/efeitos adversos , Iohexol/metabolismo , Rim/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nitrogênio/metabolismo , Nitrogênio/farmacologia , Nitrogênio/uso terapêutico , PPAR gama/genética , PPAR gama/metabolismo , PPAR gama/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Rosiglitazona/uso terapêutico , Transdução de Sinais , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ureia
14.
Life Sci ; 309: 121006, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36174711

RESUMO

AIMS: Oxidative stress and inflammatory response play a vital role in the pathogenesis of contrast-induced acute kidney injury (CI-AKI). This study investigated the effects of edaravone in rats with CI-AKI. MAIN METHODS: Male Sprague Dawley rats were randomly assigned into four groups (n = 11-14/group): control, edaravone (30 mg/kg/day intraperitoneally (IP)), CI-AKI, and edaravone with CI-AKI. The induction of CI-AKI was performed by dehydration and the administration of contrast media (iohexol) and inhibitors of prostaglandin (indomethacin) and nitric oxide synthesis (L-NAME: N-nitro L-arginine methyl ester). Edaravone was administered for two weeks before the induction of CI-AKI. Serum creatinine and urea, renal oxidative stress and inflammatory biomarkers, and histopathological alterations were evaluated after 48 h of contrast exposure. KEY FINDINGS: Rats with CI-AKI showed a significant increase in serum creatinine and urea. The levels of antioxidant biomarkers including glutathione peroxidase, superoxide dismutase and reduced glutathione were significantly decreased in CI-AKI group versus control. Pre-treatment of rats with edaravone normalized kidney function and protected the kidney from oxidative damage as demonstrated by normalization of previous biomarkers. Furthermore, edaravone partially ameliorated renal histopathological alterations relative to the CI-AKI group, notably in the nephrons. No changes were observed in inflammatory biomarkers including tumour necrosis factor-alpha and interleukin-6 among all groups. SIGNIFICANCE: The current findings suggest that edaravone could be a potential strategy to ameliorate developing CI-AKI possibly by improving renal antioxidant capacity. Further studies are warranted to expand the current understanding of the use of edaravone in the various models of AKI.


Assuntos
Injúria Renal Aguda , Iohexol , Ratos , Masculino , Animais , Edaravone/farmacologia , Edaravone/metabolismo , Iohexol/efeitos adversos , Iohexol/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Creatinina , Antioxidantes/metabolismo , Meios de Contraste/efeitos adversos , Glutationa Peroxidase/metabolismo , Ratos Sprague-Dawley , Óxido Nítrico/metabolismo , Interleucina-6/metabolismo , NG-Nitroarginina Metil Éster/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Rim/metabolismo , Glutationa/metabolismo , Biomarcadores/metabolismo , Ureia/metabolismo , Prostaglandinas/metabolismo , Indometacina/farmacologia
15.
Ren Fail ; 44(1): 1345-1355, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35938700

RESUMO

The contrast-induced acute kidney injury (CI-AKI) has been becoming the third common cause of hospital-acquired acute kidney injury. An ideal animal model is essential for understanding the pathophysiology of CI-AKI. Previous CI-AKI studies were mostly performed on rats with high-osmolar contrast medium (HOCM), which is unsuitable for transgenic researches. This study provides a novel, efficient and reproducible CI-AKI model which was developed in mouse by administrating a low-osmolar contrast medium (LOCM). First of all, we applied the frequently used pretreatments (uninephrectomy and water deprivation), which combined with HOCM on rats could induce CI-AKI, on mice with LOCM. Secondly, we attempted to find a novel pretreatment suitable for mouse and LOCM by combining two classic pretreatments(uninephrectomy, water deprivation and furosemide administration). Finally, we evaluate the kidney damage of the novel model. We found that this mouse model possessed a significant reduction in renal function, severe renal tissue damage, and increased renal tubular cells apoptosis, indicating that LOCM is a feasible inducer for CI-AKI mice model. Taken together, we found that uninephrectomy (UPHT) combined with 24 h water deprivation and furosemide administration 20 min before LOCM (iohexol, 10 ml/kg) application is a feasible pretreatment to establish a novel CI-AKI mouse model.


Assuntos
Injúria Renal Aguda , Meios de Contraste , Injúria Renal Aguda/induzido quimicamente , Animais , Meios de Contraste/toxicidade , Modelos Animais de Doenças , Furosemida/efeitos adversos , Iohexol/efeitos adversos , Rim , Camundongos , Ratos
16.
Drug Saf ; 45(9): 995-1002, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35908149

RESUMO

INTRODUCTION: The recurrence rates of immediate adverse drug reactions (ADRs) to the alternative radiocontrast media (RCM) are not well known. Previous studies suggest selection of alternative RCM considering carbamoyl side chains; however, its usefulness for preventing the recurrence of ADRs has not been clearly verified. OBJECTIVE: The aim of this study was to verify the recurrence rate of immediate ADRs according to the alternative RCM. METHOD: This retrospective study analyzed 6420 contrast-enhanced computed tomography (CT) cases of 2009 patients registered in the ADR system from 861,664 CT cases in a single tertiary hospital between 2015 and 2020. Iohexol, iopromide, iobitridol, and iopamidol were used for CT. According to the carbamoyl side chains present, iohexol belongs to group 1, iopromide belongs to groups 1 and 2, iobitridol belongs to group 2, and iopamidol belongs to group 3. RESULTS: Replacing iobitridol with iopamidol (odds ratio [OR] 2.595, 95% confidence interval [CI] 1.48-4.550) or iopromide (OR 3.354, 95% CI 1.420-7.926) as the subsequent RCM was associated with increased recurrence, while replacing iopamidol with iobitridol (OR 0.506, 95% CI 0.282-0.908) and iopromide with iohexol (OR 0.355, 95% CI 0.177-0.711) was associated with decreased recurrence. Other changes did not influence the recurrence of ADRs. CONCLUSIONS: The recurrence of immediate ADRs increased in certain RCM combinations of preceding and subsequent CT scans, and the RCMs did not show cross-reactivity. Therefore, the clinical benefit of the alternative RCM considering cross-reactivity is limited. This result suggests that the side chains of RCM do not have an important role in the recurrence of immediate ADRs.


Assuntos
Meios de Contraste , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Meios de Contraste/efeitos adversos , Humanos , Iohexol/efeitos adversos , Iopamidol/efeitos adversos , Estudos Retrospectivos , Centros de Atenção Terciária , Tomografia Computadorizada por Raios X/efeitos adversos
17.
Medicine (Baltimore) ; 101(27): e29422, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35801762

RESUMO

Although the modified barium swallowing study (MBSS) is considered the gold standard for assessing aspiration risk, aspiration of lipid-soluble barium can cause chemical pneumonitis or impair radiologic interpretation of the lungs. Water-soluble contrast agents (WSCAs) may avoid these complications while maintaining sensitivity on aspiration. This prospective, observational, case-control cohort trial evaluated all patients >3 years old referred for swallowing study from September 2015 to November 2017. Repeat evaluations of individuals were excluded. High-risk patients were evaluated by WSCA (iohexol)-based swallowing study (WSS) and others by MBSS. The study included 829 evaluations of 762 patients. After excluding 74 evaluations, 365 WSSs and 390 MBSSs were performed. The most frequent underlying condition was brain lesion, followed by aspiration pneumonia. Aspiration occurred more frequently in WSS (147 patients: 40.3%) than in MBSS (36 patients: 9.2%) (P = .00). However, neither aspiration volume (6.72 cc [3.09-10.35] vs 5.53 cc [2.21-8.85]) nor radiographic alterations differed between the 2 groups (P > .05). Moreover, the swallowed (16.62 cc [8.45-24.79]) and aspirated amounts of iohexol were not correlated with radiologic changes or deterioration (P > .05). Switching to oral feeding following WSS was more frequent (164 patients: 44.9%), whereas aspiration pneumonia was not (P = .00). WSS did not prolong the interval to patient discharge (P = .06) or induce an allergic reaction or chemotoxicity over 1 week. The absence of aspiration-induced complications and adverse drug effects suggests that, compared with MBSS, WSS may increase aspiration sensitivity and early switching to oral feeding.


Assuntos
Transtornos de Deglutição , Pneumonia Aspirativa , Bário , Estudos de Casos e Controles , Pré-Escolar , Meios de Contraste/efeitos adversos , Deglutição , Transtornos de Deglutição/induzido quimicamente , Transtornos de Deglutição/complicações , Transtornos de Deglutição/diagnóstico por imagem , Humanos , Iohexol/efeitos adversos , Pneumonia Aspirativa/induzido quimicamente , Pneumonia Aspirativa/diagnóstico por imagem , Estudos Prospectivos , Água
19.
Thyroid ; 32(6): 739-743, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35180827

RESUMO

Background: Failure to escape from the Wolff-Chaikoff effect (WCE) causes hypothyroidism. Methods: This is the first report of myxedema coma after iohexol administration. The failure of the escape phenomenon in this patient was longer than existing reports. Results: The patient received 42,000 mg of iodine in iohexol cumulatively and developed myxedema coma after 16 days. She was subsequently found to have pre-existing primary hypothyroidism that was treated with levothyroxine 50 µg daily, but had defaulted treatment. She was discharged with levothyroxine 100 µg daily and this was weaned to 50 µg daily over 12 months. Conclusions: Iodine-based contrast media (ICM) can aggravate primary hypothyroidism. In severe cases, it may precipitate myxedema coma. Patients with thyroid disorders should be informed to monitor for aggravation of their symptoms after ICM administration. Long-term follow-up of thyroid function may be needed in patients who fail to escape from the WCE.


Assuntos
Hipotireoidismo , Iodo , Mixedema , Coma/induzido quimicamente , Feminino , Humanos , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Iodetos , Iohexol/efeitos adversos , Mixedema/induzido quimicamente , Mixedema/tratamento farmacológico , Tiroxina/uso terapêutico
20.
Chem Res Toxicol ; 35(2): 244-253, 2022 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-35081708

RESUMO

Iohexol, the raw material of nonionic X-ray computed tomography (X-CT) contrast medium, is usually injected into the vein before CT angiography diagnosis. It is used for angiography, urography, and lymphography. With the advantages of low contrast density and good tolerance, it is currently one of the most popular contrast media. However, the renal toxicity of iohexol seriously affects its safety use. Therefore, it is of great importance to identify new potential diagnostic biomarkers and therapeutic targets in the process of contrast medium-induced acute kidney injury (CI-AKI) in order to safely use iohexol in clinical practice. In this study, in order to understand the metabolic mechanism of CI-AKI, ultra-high-performance liquid chromatography/quadrupole-Orbitrap-mass spectrometry and 1H NMR-based metabolomic techniques were utilized to study the metabolic spectra of kidney, plasma, and urine from CI-AKI rats, and a total of 30 metabolites that were closely related to kidney injury were screened out, which were mainly related to 9 metabolic pathways. The results further indicated that iohexol might intensify kidney dysfunction in vivo by disrupting the metabolic pathways in the body, especially through blocking energy metabolism, amino acid metabolism, and promoting inflammatory reactions.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Iohexol/efeitos adversos , Injúria Renal Aguda/diagnóstico por imagem , Injúria Renal Aguda/metabolismo , Animais , Cromatografia Líquida , Meios de Contraste/administração & dosagem , Meios de Contraste/metabolismo , Injeções Subcutâneas , Iohexol/administração & dosagem , Iohexol/metabolismo , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Ratos , Ratos Sprague-Dawley , Ultrassonografia
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