Current Pharmaceutical Design - Volume 25, Issue 44, 2019

Contrast-induced acute kidney injury (CIAKI) is a severe complication associated with the use of iodinated contrast media (CM); a sudden but potentially reversible fall in glomerular filtration rate (GFR) typically occurring 48-72 hours after CM administration. Principal risk factors related with the presentation of CIAKI are preexisting chronic kidney disease and diabetes mellitus. Studies on CIAKI present considerable complexity because of differences in CM type and dose, controversies in definition and baseline comorbidities. Despite that, it should be noted that CIAKI poses a serious health problem because it is a very common cause of hospitalacquired AKI, linked to increased morbidity and mortality and utilizing growing healthcare resources. The pathogenesis of CIAKI is heterogeneous and, thus, is incompletely understood. Three basic mechanisms appear to simultaneously occur for CIAKI development: Renal vasoconstriction and medullary hypoxia, tubular cell toxicity and reactive oxygen species formation. The relative contribution of each one of these mechanisms is unknown but they ultimately lead to epithelial and endothelial cell apoptosis and GFR reduction. Further research is needed in order to better clarify CIAKI pathophysiology and accordingly introduce effective preventive and therapeutic strategies.

Iodinated Contrast Media (CM) has a plethora of applications in routine non-invasive or percutaneous invasive imaging examinations and therapeutic interventions. Unfortunately, the use of CM is not without complications, with contrast-induced acute kidney injury (CI-AKI) being among the most severe. CI-AKI is a syndrome defined as a rapid development of renal impairment after a few days of CM endovascular injection, without the presence of any other underlying related pathologies. Although mostly transient and reversible, for a subgroup of patients with comorbidities related to renal failure, CI-AKI is directly leading to longer hospitalization, elevated rates of morbidity and mortality, as well as the increased cost of funding. Thus, a need for classification in accordance with clinical and peri-procedural criteria is emerged. This would be very useful for CI-AKI patients in order to predict the ones who would have the greatest advantage from the application of preventive strategies. This article provides a practical review of the recent evidence concerning CI-AKI incidence, diagnosis, and sheds light on prevention methods for reducing contrast use and avoiding AKI during endovascular procedures. In conclusion, despite the lack of a specific treatment protocol, cautious screening, assessment, identification of the high-risk patients, and thus the application of simple interventions -concerning modifiable risk factors- can significantly reduce CI-AKI risk.

Background: Carbon dioxide (CO2) exists in nature around us. In the middle of the 20th century, the intraluminal injection of CO2 demonstrated similar results to those of Digital Subtraction Angiography (DSA) with an iodinated contrast agent (ICA). Since then, the technology behind CO2 DSA has developed significantly. Objective: The aim of this study is to inform physicians about the unique properties of CO2 and its physiology after intraluminal injection. Methods: An extensive search for English literature on the properties of CO2 and the physiology of intraluminal administration was conducted using Pubmed. Results: There is sufficient literature on the properties of CO2 and the physiology of CO2 DSA. A review of this literature explains what happens to the human organism after the injection of CO2. Conclusion: There is enough evidence that CO2 DSA is both effective, diagnostic and safe, but the properties of CO2 should be taken under consideration as complications occur, although rarely.

Background: Traditional contrast media containing iodine remain the gold standard for vessel visualization during endovascular procedures. On the other hand, their use has several side effects and implications and may cause contrast medium-induced nephropathy. Carbon dioxide (CO2) angiography is an old alternative technique used only for critical patients in order to prevent kidney damages or allergic reactions. Zero contrast procedure: The availability of automated CO2 injectors has led to an increase in the use of CO2 angiography, providing an option for zero contrast interventions, preserving patient renal function and saving costs for the hospital facility. Taking advantage of the properties of CO2 gas, it is possible to improve the performance of some complex procedures such as atherectomy and the detection of type II endoleaks after EVARs. However, a learning curve is needed to get good imaging, and learn about the qualities and limitations of the technique. Conclusions: The use of automatic delivery systems for CO2 angiography appears to be a good choice for the use of CO2 as the first imaging option. The standardization of injection protocols and the extensive use of this technique could lead to significant benefits both for the patient's prospects and health facilities.

Background: Acute Kidney injury is recognised to occur after administration of iodinated contrast during endovascular interventions for peripheral arterial disease. There are no standardised protocols for contrast delivery during infrainguinal angiography. Objective: The objective of this paper is to review published practice regarding the technique of conventional infrainguinal angiography and intervention, and describe a standard set of subtraction views, injection rates and contrast volumes for infrainguinal angioplasty. Methods: Database searches and review of papers containing (Angioplasty or Angiography) and (“lower limb” or peripheral or infrainguinal) and (method or technique or guidelines or protocol) was performed and defined procedures assessed. Results: A small number of papers provided specific technical details relating to contrast volumes and angiography views. There was considerable variation from authors who have described the contrast volumes used for lower limb angiography. We describe our simple and consistent method. The precise pathophysiology of contrast related nephropathy is under scrutiny. There is interest in new technology to minimise contrast induced kidney injury. Conclusion: Few publications specify iodinated contrast doses, injection volumes or imaging views for infrainguinal arteriography. Standard infrainguinal angioplasty can be performed with conventional equipment using relatively small volumes of contrast by following a systematic technique.

Aim: The effect of endovascular aneurysm repair in patients treated for abdominal aortic aneurysm has not been clearly defined. The objective of the present article was to provide a contemporary literature review and perform an analysis to determine the effect of EVAR on renal function in the early post-operative period and during follow-up. Methods: A systematic review of the literature was undertaken to identify all studies reporting the effect of EVAR on renal function. Outcome data were pooled and combined overall effect sizes were calculated using fixed or random-effects models. Results: Thirty-two studies reporting on 24846 patients were included. Acute renal failure after EVAR occurred with an estimated frequency of 9% (95%CI: 5-16%; I2=97%). Median follow-up period was 19.5 months (range 1-60 months). The estimated frequency of chronic renal failure during follow-up was 7% (95%CI: 3-17%; I2=98%). Hemodialysis was required in 2% (1-3%; I2=97%) of the cases. Conclusion: High-level evidence demonstrating the effect of EVAR on the incidence of acute and chronic renal failure is lacking. Based on the current available data, nearly 10% of patients undergoing EVAR for AAA have an increased risk for renal dysfunction after the procedure. Whether this deterioration may lead to a worse outcome has not been adequately proved.

Background: Complex endovascular repair of abdominal aortic aneurysm carries higher perioperative morbidity than standard infrarenal endovascular repair. Objective: This study reviews the incidence and associated factors of acute kidney injury in complex aortic endovascular repair of juxtarenal, pararenal, and thoracoabdominal aortic aneurysms. Methods: A literature review was performed for all studies on the endovascular repair of juxtarenal, pararenal, and thoracoabdominal aneurysms that evaluated rates of acute kidney injury as an outcome. Outcomes were further analyzed by the level of anatomic complexity and method of repair. Results: 52 studies met inclusion criteria, with a total of 5454 individuals undergoing repair from 2004 to 2017. The overall rate of acute kidney injury ranged widely from 0 to 41%, with a rate of hemodialysis from 0 to 19% (temporary) and 0 to 14% (permanent). Increasing anatomic complexity was associated with higher rates of acute kidney injury. Mode of endovascular repair, learning curve effect, and preoperative chronic renal insufficiency did not demonstrate any associations with the outcome. Conclusion: Published rates of acute kidney injury in complex aortic aneurysm repair vary widely with few definitively associated factors other than increasing anatomic complexity and operative time. Further study is needed for the identification of predictors related to postoperative acute kidney injury.

The widespread adoption of endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA) is due to the obvious advantages of the procedure compared to the traditional open repair. However, these advantages have to be weighed against the increased risk of renal dysfunction with EVAR. The evaluation of the perioperative renal function after EVAR has been hampered by the lack of sensitive and specific biochemical markers of acute kidney injury (AKI). The purpose of this study was to summarize all novel renal biomarkers and to evaluate their clinical utility for the assessment of the kidney function after EVAR. A systematic review of the current literature, as the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines, was performed to identify relevant studies with novel renal biomarkers and EVAR. Pubmed and Scopus databases were systemically searched. Studies reporting on thoracic endovascular aortic repair (TEVAR), case reports, case series, letters to the editor, and systematic reviews were excluded. Neutrophil-Gelatinase-Associated Lipocalin, Cystatin C, Liver-type fatty-acid-binding protein were the most common among the eligible studies while Interleukin-18, Retinol binding protein, N-acetyle-b-D-glucosaminidase and microalbumin have a sparse appearance in the literature. These biomarkers have been assessed in plasma as well as urine samples with each sample material having its own advantages and drawbacks. Which of these biomarkers has the most potential for assessing postoperative renal failure after EVAR, remains to be proved. The few studies presented in the literature show the potential clinical utility of these biomarkers, but larger studies with longer follow-up are required to determine the precise relationship between these biomarkers and postoperative acute kidney injury.

Due to their versatile biological activity, Azoles are widely studied in pharmacochemistry. It is possible to use them in many applications and in studies aimed at discovering antiparasitic, antineoplastic, antiviral, antimicrobial compounds; and in the production of materials for treatment of varied pathologies. Based on their biological activity, our review presents several studies that involve this class of organic compounds. A bibliographic survey of this type can effectively contribute to pharmaceutical sciences, stimulating the discovery of new compounds, and structural improvements to biological profiles of interest. In this review, articles are discussed involving the synthesis of new compounds and chemoinformatic contributions. Current applications of azoles in both the pharmaceutical and agri-business sectors are well known, yet as this research highlights, azole compounds can also bring important contributions to the fight against many diseases. Among the heterocyclics, azoles are increasingly studied by research groups around the world for application against tuberculosis, HIV, fungal and bacterial infections; and against parasites such as leishmaniasis and trypanosomiasis. Our hope is that this work will help arouse the interest of research groups planning to develop new bioactives to fight against these and other diseases.

Background: Antibacterial multidrug resistance has emerged as one of the foremost global problems affecting human health. The emergence of resistant infections with the increasing number of multidrug-resistant pathogens has posed a serious problem, which required innovative collaborations across multiple disciplines to address this issue. Methods: In this review, we will explain the mechanisms of bacterial multidrug resistance and discuss different strategies for combating it, including combination therapy, the use of novel natural antibiotics, and the use of nanotechnology in the development of efflux pump inhibitors. Results: While combination therapy will remain the mainstay of bacterial multi-drug resistance treatment, nanotechnology will play critical roles in the development of novel treatments in the coming years. Conclusion: Nanotechnology provides an encouraging platform for the development of clinically relevant and practical strategies to overcome drug resistance in the future.

Aims: To compare the efficacy of pemafibrate (PF) and fenofibrate (FF) in treating dyslipidemia. Methods: A comprehensive search was performed on the public database to identify relevant randomized controlled trials (RCTs), which compared the effects of PF and FF treatment in lipid parameters among patients with dyslipidemia. Mean difference (MD) and 95% confidence intervals (CI) were pooled for continuous outcomes, whereas odds ratio (OR) and 95% CI were calculated for dichotomous outcomes. Results: Three RCTs were included with a total of 744 patients (PF=547 and FF=197). Compared with the FF group (100mg/day), PF group (0.05 to 0.4mg/day) had a better effect on reducing triglycerides (TGs) (MD, -8.66; 95%CI, -10.91 to -6.41), very low-density lipoprotein cholesterol (VLDL-C, MD, -12.19; 95%CI, -15.37 to - 9.01), remnant lipoprotein cholesterol (MD, -13.16; 95%CI, -17.62 to -8.69), apolipoprotein-B48 (ApoB48, MD, -12.74; 95%CI, -17.71 to -7.76) and ApoCIII (MD, -6.25; 95%CI, -11.85 to -0.64). Although a slightly LDL-Cincreasing effect was found in PF-treated group (MD, 3.10; 95%CI, -0.12 to 6.09), the levels of HDL-C (MD, 3.59; 95%CI, 1.65 to 5.53) and ApoAI (MD, 1.60; 95%CI, 0.38 to 2.82) were significantly increased in the PF group. However, no significant difference was found in the level of total cholesterol (MD, 0.01; 95%CI, -1.37 to - 1.39), non-HDL-C (MD, -0.06; 95%CI, -1.75 to 1.63), ApoB (MD, 0.39; 95%CI, -1.37 to 2.15) and ApoAII (MD, 3.31; 95%CI, -1.66 to 8.29) between the two groups. In addition, the incidence of total adverse events (OR, 0.68; 95%CI, 0.53 to 0.86) and adverse drug reactions (OR, 0.36; 95%CI, 0.24 to 0.54) was lower in the PF group than that in the FF group. Conclusions: Pemafibrate tends to have better efficacy in treating dyslipidemia than fenofibrate.