Pathogenesis Of Contrast-induced Nephropathy Research Articles

Serum total bilirubin level is associated with contrast induced nephropathy after primary percutaneous coronary intervention.

Contrast Induced Nephropathy (CIN) is a major complication of angiographic procedures. Primary percutaneous coronary intervention (pPCI) is the preferred treatment for ST-segment elevation myocardial infarction (STEMI) but is associated with a risk of CIN. Oxidative stress and free radical damage play a role in the pathogenesis of CIN. Bilirubin has anti-inflammatory and antioxidant activity and has been shown to have a protective effect on endothelial cells. The present study aimed to assess the association between serum bilirubin level and development of CIN after pPCI. Sequential STEMI patients (n = 595) who underwent pPCI between January 2021 and December 2022 were enrolled. Among the participants, 116 (19.5%) developed CIN. Serum total bilirubin level was significantly lower in the CIN group (P = .001). In multivariate logistic regression analysis, serum bilirubin level was found as an independent predictor of CIN. Age, gender, contrast volume, and white blood cell count were other independent predictors of CIN. A higher serum bilirubin level is associated with a lower risk of CIN in the present study. In STEMI patients undergoing pPCI, serum bilirubin level may be helpful to predict the risk of CIN and may help ensure early initiation of preventive treatment and careful follow-up.

Contrast-induced nephropathy (CIN) - epidemiology, risk factors and prevention

Introduction: Contrast-induced nephropathy is one of the most serious adverse effects of radiocontrast agents usage. It is currently listed in the literature as the third most common cause of iatrogenic acute kidney injury. Aim of the study: The aim of this study is to provide an overview of the extent, severity and prevention of CIN. It is to shed a broader light on this disease entity and be a helpful resource in the future for other clinicians struggling with CIN. Methods and materials: A literature review was conducted using the PubMed database, using the keywords: "contrast-induced nephropathy"; "acute kidney injury"; "contrast media". Results: Pathogenesis of CIN is not entirely clear. There are many risk factors being e.g. diabetes, chronic kidney disease, advanced age (patients over 75 years old). Prevention methods include restricting contrast volume to a minimum, balancing the patient's volaemia before contrast administration or perioperative saline hydration to normalise volaemia. Conclusion: CIN is a significant health problem, which can be a life threat. Despite the fact that the exact pathogenesis of the condition still remains unknown, the CIN prophylaxis becomes more and more effective due to better recognition of risk factors and the usage of adequate prevention measures appropriate to the patients' condition. More studies, with larger test groups, are needed to better define both the pathomechanism of contrast-induced acute kidney injury and new, more effective ways of prevention and treatment of this condition.

POS-311 Long-term effects of contrast-enhanced intervention on progression of chronic kidney disease: A retrospective cohort study

In recent years, with increasing importance of accurate diagnosis and treatment, imaging interventions using a contrast medium have become inevitable. However, iodinated contrast media often cause hypersensitivity, and at times even to severe shock. Despite years of research, the pathogenesis of contrast-induced nephropathy (CIN) is not fully elucidated. Elderly people and those with chronic kidney disease (CKD) are especially at risk. CIN develops in 4–11% of patients with moderate renal dysfunction.

Vitamin C in the Prevention of Contrast-induced Nephropathy among High-risk Patients Undergoing Coronary Angiogram: A Meta-analysis

Background: Contrast-Induced nephropathy (CIN) is one of the leading causes of acute kidney injury. The most common procedures associated with CIN are coronary angiography and contrast enhanced computed tomography (CT) [1]. The most common definition in use is an increase in serum creatinine (SCr) of >25% of the baseline values occurring following the intravascular administration of contrast media without an alternative explanation [2]. Generation of reactive oxygen species is thought to play a role in the pathogenesis of CIN, hence researches have been conducted into the potential role of antioxidants in the prevention of contrast-induced nephropathy [3]. Vitamin C, a potent antioxidant in humans has the ability to oxidize free radicals, and has been studied in different trials to measure its ability to prevent CIN among patients undergoing coronary angiogram.
 Objective: To determine if vitamin C prevents CIN among High-risk patients (Creatinine Clearance <60 ml/min/m2, Diabetics, and on administration of high-volume contrast media).
 Methodology: All studies, limited to randomized clinical trials were sought for this analysis through PubMed, the Cochrane Library, ClinicalTrials.gov. Database was searched using the terms “vitamin C”, “Prevention”, “acute kidney injury” and “contrast-induced nephropathy”. Adult patients (40-90 years old) with Creatinine Clearance of <60 ml/min/m2 or baseline creatinine >1.2 mg/dl, Diabetes Mellitus Type II, and were administered with high-volume contrast media (>100ml) undergoing coronary angiogram were included in the study. Exclusion Criteria were patients with normal baseline renal function, without risk factors for CIN, with EGFR < 30 ml/min/m2, with regular intake of Vitamin C and were on dialysis. Statistical data were obtained using Review Manager (RevMan) Version 5.3 freeware program. P Value was obtained using the Cochran–Mantel–Haenszel test (CMH). Included patients were given Vitamin C at doses of 1 gram to 3 grams, taken orally or administered intravenously pre-and post coronary angiogram.
 Results: Seven hundred and one (N=701) patients were included in this meta-analysis. CIN occurred in 3.5% of patients (N=25) in the ascorbic acid group and in 6% of patients (N= 42) in the placebo group (p value of 0.03).
 Conclusion: Vitamin C given at doses 1 gram to 3 grams in combination with hydration prior to coronary angiogram may have a significant effect in the prevention of CIN in high-risk patients.

Dysregulation of HULC promotes contrast-induced nephropathy (CIN) via regulating signaling pathway of miRNA-512 and prostaglandin E1 (PGE1)

It has been shown that contrast-induced nephropathy (CIN) can be attenuated by the administration of PGE1. As an enzyme responsible for the production of PGE1, PTGS1 was confirmed in this study as a miR-512 target. Meanwhile, HULC has been identified as a competing endogenous RNA of miR-512. Therefore, in this study, we tested the diagnostic value of HULC and miR-512 in subjects with or without CIN. In addition, we evaluated the regulatory relationship among HULC, miR-512, PTGS1 and PGE1 in vitro. We enrolled 320 patients with coronary heart disease and divided them into a CIN group and a non-CIN group. Subsequently, we detected the differential expression of miR-512, HULC and PGE1 in the two groups. We also used a dual luciferase reporter assay to evaluate the regulatory relationship among HULC, miR-512, PTGS1 and PGE1 in THP-1 cells. In patients with CIN, the expression levels of HULC and PGE1 were lower, but the expression level of miR-512 was higher. MiR-512 could directly bind to and negatively regulate the expression of PTGS1 and HULC. The expression of HULC was positively correlated with the expression of PTGS1 and PGE1, while negatively correlated with the expression of miR-512. The findings of this study demonstrated that deregulation of lncRNA-HULC/miR-512/PTGS1/PGE1 might be involved in the pathogenesis of CIN.

ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography.

Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application.Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration.Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 μmol/L (area under the curve: 0.854, 95% confidential interval: 0.767–0.941, P < 0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 μmol/L (area under the curve: 0.750, 95% confidence interval: 0.602–0.897, P = 0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study cohort. The impact of ADMA on MARE was independent of such known CIN risk factors as anemia, pre-existing renal failure, pre-existing heart failure, and diabetes.ADMA concentration in plasma is a promising novel biomarker of major contrast-induced nephropathy-associated events 90 days after contrast media exposure.

Effect of radiographic contrast media onrenal perfusion - First results.

Intra-arterial administration of radiographic contrast media (CM) is discussed to impair renal perfusion. The pathogenesis of contrast-induced Nephropathy (CIN) is still not clarified. This trial was performed to prove the effects of two CM with different molecular structure on renal perfusion. A prospective, randomized study on 16 pigs was designed to compare the outcome after application of a low-osmolar iodinated CM (770 mOsm/kg H2O - Group1) and an iso-osmolar iodinated CM (290 mOsm/kg H2o - Group2).Color Coded Doppler Sonography (LOGIQ E9, GE, Milwaukee, USA) was applied for measuring the Renal Resistive Index (RRI) before and after the first, fifth, and tenth bolus of CM. Statistics was performed using analysis of variance for repeated measurements with the Factor "CM". All flow spectra were documented free of artifacts and Peak Systolic Velocity (PSV), Enddiastolic Velocity (EDV) and RRI respectively could be calculated. Mean PSV in Group 1 led to a decrease while in Group 2 PSV showed a significant increase after CM (p = 0,042). The course of the mean EDV in both groups deferred accordingly (p = 0,033). Mean RRI over time significantly deferred in both groups (p = 0,001). It showed a biphasic course in Group 2 and a decrease over time in Group 2. While iso-osmolar CM induced an increase of PSV and EDV together with a decrease of RRI, low-osmolar CM could not show this effect or rather led to the opposite.

Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.

With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

Sildenafil prevents renal dysfunction in contrast media-induced nephropathy in Wistar rats.

Contrast-induced nephropathy (CIN) is an iatrogenic medical event in stable cardiology patients that may lead to acute renal failure. There is no current successful therapy to manage CIN. Increasing evidence in experimental models and humans has suggested that this disease is associated with renal tubular and vascular injury triggered by oxidative stress. Considering the importance of reactive oxygen species (ROS) generation in the pathogenesis of CIN, the goal of the present study was to evaluate the effects of sildenafil on CIN development. Male Wistar rats were divided into control, CIN, and CIN pretreated with sildenafil (50 mg/kg/day). CIN was induced by water deprivation, NG-nitro-L-arginine methyl ester + indomethacin injections (10 mg/kg, intraperitoneally) and intravenous iohexol administration (3 g/kg). Renal function was evaluated through glomerular filtration rate (GFR), renal blood flow (RBF), plasma creatinine, uremia, and proteinuria. Oxidative stress was assessed by flow cytometry for intracellular ROS. Treatment with sildenafil attenuated the marked reduction of GFR and RBF in the CIN group. Moreover, sildenafil treatment in CIN rats reduced plasma creatinine, uremia, and proteinuria. Flow cytometry demonstrated that sildenafil attenuated the ROS production in the CIN group. These data suggest that sildenafil may be a new therapeutic agent to prevent CIN through its ability to preserve renal function and attenuate oxidative stress.

The possible role of interleukin-33 as a new player in the pathogenesis of contrast-induced nephropathy in diabetic rats

Introduction: Patients with diabetic kidney disease (DKD) are more prone to contrast-induced nephropathy (CN). Apoptosis and autophagy were found to be essential in the pathogenesis of DKD. Interleukin-33 (IL-33) is a cytokine, but its role in DKD and CN is unknown. As IL-33 is modulated by apoptosis, we aimed to determine the relationship between IL-33 apoptosis and autophagy in DKD with CN. Materials and methods: Thirty male Sprague–Dawley rats were enrolled and randomly allocated into three groups. The first group was comprised of healthy rats (HRs), whereas the other two groups were made up of diabetic rats (DRs) and diabetic rats with CN (DRs + CN). All groups except the HRs received 50 mg/kg/day of streptozotocin (STZ). The DRs + CN group was induced by administering 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. Results: We observed increased IL-33 in the kidney tissue following induction of CN in the DRs. The DRs showed moderate immunopositivity, and the DRs + CN showed severe immunopositivity for caspase-3, cleaved caspase-3, caspase-8, caspase-9, LC3B, and Beclin-1 in tubular cells and glomeruli. The DRs also showed moderate immunopositivity in tubular cells, and the DRs + CN group showed severe immunopositivity for IL-33 in tubular cells. Increased caspase-3 was found in both glomeruli and tubuli; however, we could not demonstrate IL-33 in glomeruli. This could be secondary to inactivation of IL-33 via increased caspase-3 activity. Conclusion: The release of IL-33 from necrotic cells might induce autophagy, which can further balance the effects of increased apoptosis secondary to CN in DKD.

Targeting HO-1 by Epigallocatechin-3-Gallate Reduces Contrast-Induced Renal Injury via Anti-Oxidative Stress and Anti-Inflammation Pathways.

Both oxidative stress and inflammation are involved in the pathogenesis of contrast-induced nephropathy (CIN). Epigallocatechin-3-gallate (EGCG), a purified catechin from green tea, has antioxidant and anti-inflammatory effects. However, it is unknown whether or not EGCG is effective in treating CIN. Our present study found that intravenous administration of EGCG, either before or just after the establishment of CIN, had a protective effect, determined by normalization of serum creatinine and blood urea nitrogen levels, improvement in renal histopathological scoring and alleviation of apoptosis, accompanied by decreased oxidative stress and inflammation. Because EGCG is a potent inducer of the antioxidant heme oxygenase-1 (HO-1), we studied HO-1 signaling in CIN. HO-1 levels were increased in CIN; treatment with EGCG further increased HO-1 levels, accompanied by an increase in Nrf2, a regulator of antioxidant proteins. Interestingly, blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) prevented the protective effect of EGCG on CIN. ZnPP also blocked the ability of EGCG to increase the activity of an antioxidant (superoxide dismutase), and decrease markers of oxidative stress (myeloperoxidase and malondialdehyde) and inflammation (myeloperoxidase and IL-1β), indicating that HO-1 is the upstream molecule that regulates the EGCG-mediated protection. To determine further the role of HO-1 on the EGCG-mediated inhibition of inflammation, we studied the effect of EGCG on the NLRP3 inflammasome, an upstream signaling of IL-1β. EGCG down-regulated NLRP3 expression, which was blocked by ZnPP, indicating that HO-1 links EGCG with NLRP3. Therefore, EGCG, via up-regulation of HO-1, protects against CIN by amelioration of oxidative stress and inflammation.

Sulforaphane Attenuates Contrast-Induced Nephropathy in Rats via Nrf2/HO-1 Pathway.

Background. Oxidative stress plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of this study was to investigate the antioxidant effects of sulforaphane (SFN) in a rat model of CIN and a cell model of oxidative stress in HK2 cells. Methods. Rats were randomized into four groups (n = 6 per group): control group, Ioversol group (Ioversol-induced CIN), Ioversol + SFN group (CIN rats pretreated with SFN), and SFN group (rats treated with SFN). Renal function tests, malondialdehyde (MDA), and reactive oxygen species (ROS) were measured. Western blot, real-time polymerase chain reaction analysis, and immunohistochemical analysis were performed for nuclear factor erythroid-derived 2-like 2 (Nrf2) and heme oxygenase-1 (HO-1) detection. Results. Serum blood urea nitrogen (BUN), creatinine, and renal tissue MDA were increased after contrast exposure. Serum BUN, creatinine, and renal tissue MDA were decreased in the Ioversol + SFN group as compared with those in the Ioversol group. SFN increased the expression of Nrf2 and HO-1 in CIN rats and in Ioversol-induced injury HK2 cells. SFN increased cell viability and attenuated ROS level in vitro. Conclusions. SFN attenuates experimental CIN in vitro and in vivo. This effect is suggested to activate the Nrf2 antioxidant defenses pathway.

Contrast-induced nephropathy: pathogenesis and new therapeutic options for prevention.

Contrast-induced nephropathy is a common cause of inpatient and outpatient acute renal failure. The pathogenesis is complex adding difficulty to its management. Several preventive measures that involved the use of intravenous fluids and oral agents have been implemented in human studies with heterogeneous results because of the disparity in defining changes in glomerular filtration rate after renal injury. New preventive techniques based on the pathogenesis of contrast-induced nephropathy are being applied to human subjects with preliminary good outcomes. Future randomized trials will give us the opportunity to elucidate its benefits.

Contrast-induced nephropathy: a review of literature

Today, radiological procedures using intravascular iodinated contrast media are being widely used for the diagnoses and treatment of various diseases, which highlight one of the main etiologies of contrast-induced nephropathy and hospital-acquired renal failure. Contrast-induced nephropathy development is associated with longer hospital stay, increase in both short- and long-term morbidity and mortality, in addition to greater health care costs.The pathogenesis of contrast-induced nephropathy has not yet been fully explained in detail; however it is clear that the root concept is medullary hypoxia-induced renal tubular damage.Chronic kidney disease and diabetes mellitus are the two most important intrinsic predisposing factors to contrast-induced nephropathy. As no treatment can specifically target contrast-induced nephropathy, the main goal for clinicians is prevention of the disease. While the best approach for achieving this goal is still controversial, optimization of the patients’ circulating volume remains the only proven strategy to date. As contrast-induced nephropathy is a potentially preventable clinical condition, its better understanding will lead to better prevention of this disease. Hereby, we aimed to discuss contrast-induced nephropathy from 7 different aspects in clinical practice: 1) clinical aspect, 2) prevalence, 3) pathophysiology, 4) contrast agents and renal cell apoptosis, 5) different contrast media, 6) prevention, and 7) treatment.

Circulating tumour necrosis factor receptors 1 and 2 predict contrast-induced nephropathy and progressive renal dysfunction: a prospective cohort study.

Contrast-induced nephropathy (CIN) is an important cause of hospital-acquired acute kidney injury. An accurate understanding of the pathogenesis of CIN is crucial. The aim of this study was to evaluate the clinical role of circulating tumour necrosis factor receptors (cTNFRs) in CIN. From May 2013 to February 2014, 262 patients who underwent coronary angiography and/or percutaneous coronary intervention at Seoul National University Boramae Medical Center were enrolled. CIN was defined as either an increase in serum creatinine ≥ 22.1 μmol/L or ≥ 25% within 48 h after the procedure. Diabetes and chronic kidney disease accounted for 27.5% and 17.6% of the patients, respectively, and the mean age was 65 years. All patients received fluid therapy, and 36.3% underwent percutaneous coronary intervention. A total of 4.2% of the patients developed CIN; younger age, underlying diseases (e.g., stroke and chronic kidney disease), the use of N-acetylcysteine, and elevated concentrations of ln(cTNFRs) were associated with development of CIN. Increased values of ln(cTNFR1) (OR 6.32, 95% CI 2.46-16.28, P < 0.001) and ln(cTNFR2) (OR 3.24, 95% CI 1.26-8.31, P = 0.015) were significantly associated with CIN after adjusting for other risk factors, including baseline renal function. Moreover, an increase of cTNFRs levels was independently correlated with the deterioration of renal function. Markedly elevated concentrations of circulating TNFRs were correlated with the occurrence of CIN and significantly associated with prolonged renal dysfunction regardless of the development of CIN.

Oxidative stress and paraoxonase 1 activity predict contrast-induced nephropathy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Reactive oxygen species have been implicated in the pathogenesis of contrast-induced nephropathy (CIN). We investigated the relationship between CIN with paraoxonase 1 (PON-1) activity and oxidative stress markers (total antioxidant status [TAS], total oxidant status [TOS], and oxidative stress index [OSI]) in patients with anterior ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention; 289 consecutive patients with STEMI were prospectively included. The patients were divided into 2 groups: CIN (n = 69) and non-CIN (n = 220). Activity of PON-1 and TAS levels were significantly lower and OSI and TOS levels were significantly higher in patients with CIN compared to the non-CIN group (P < .05, for all). On multivariate logistic regression analysis, PON-1 activity and OSI as well as the amount of contrast medium and diabetes were independent predictors for CIN in patients with anterior STEMI. Activity of PON-1 and oxidative stress may play a role in the pathogenesis of CIN.

GSPE is superior to NAC in the prevention of contrast-induced nephropathy: Might this superiority be related to caspase 1 and calpain 1?

AimsOur study was intended to evaluate the role of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), caspases 1 and 3 and calpain 1 in the pathogenesis of contrast-induced nephropathy (CIN) and to compare the protective effects of N acetyl cysteine (NAC) and grape seed proanthocyanidin extract (GSPE) against the development of CIN. Main methods32 rats were divided into four groups; control, contrast media (CM), CM+NAC and CM+GSPE. CIN was induced by administration of 7ml/kg diatrizoate. The experiment was discontinued on the ninth day. Blood was collected for blood urea nitrogen (BUN) and creatinine measurement. Rat kidney tissues were removed for histopathological evaluation and the investigation of caspases 1 and 3, iNOS, eNOS, TUNEL and calpain 1. Key findingsA significant increase in BUN, creatinine, renal histopathological injury, TUNEL, caspases 1, 3, calpain 1, iNOS and eNOS was observed in the CM group compared to the control group. There was amelioration in all these parameters in the CM+GSPE group, while there was no significant amelioration in BUN, creatinine and renal histopathological injury in the CM+NAC group. In addition, calpain 1 staining and creatinine were significantly lower in the CM+GSPE group compared to the CM+NAC group. SignificanceOur study showed, for the first time in the literature, that GSPE has a greater renoprotective effect compared with NAC and that this effective protection may be related to decrease in calpain 1 levels.

Contrast-induced nephropathy; A literature review.

Contrast-induced nephropathy (CIN) is a common cause of acute kidney dysfunction. Directory of Open Access Journals, Google Scholar, PubMed, EBSCO and Web of Science have been searched. It is necessary to identify at risk patients at early stages to implement preventive strategies to decrease the incidence of this nephropathy. However, mechanisms of CIN have not fully explained yet. It seems that mechanisms which mediated by nitric oxide and prostaglandin-induced vasodilatation have been played a crucial role in the CIN. Hemodynamic changes of renal blood flow, which causes hypoxia in the renal medulla and direct toxic effects of contrast media on renal cells, are thought to contribute to the pathogenesis of CIN. Contrast media is normally divided into iso-osmolar, low-osmolar, and high-osmolar. N-acetylcysteine is considered as one of the best choices to prevent CIN in high-risk groups. The first aim to prevent CIN is identifying high-risk subjects and controlling associate risk factors. As significant differences existed between contrasts agents due to their physicochemical properties, low-osmolar or iso-osmolar contrast media should be used to prevent CIN in at-risk patients. The volume of contrast media should be as low as possible.

Magnolin protects against contrast-induced nephropathy in rats via antioxidation and antiapoptosis.

Background. Magnolin is the major active ingredient of the herb Magnolia fargesii which has anti-inflammatory and antioxidative effects. Oxidative stress and apoptosis are involved in the pathogenesis of contrast-induced nephropathy (CIN). We hypothesize that Magnolin could protect against CIN through antioxidative and antiapoptotic properties. Methods. To test whether Magnolin could attenuate CIN, oxidative stress and apoptosis, in vivo and in vitro, we utilized a rat model of ioversol-induced CIN and a cell model of oxidative stress in which HK2 cells were treated with H2O2. Rats were assigned to 4 groups (n = 6 per group): control group, ioversol group (ioversol-induced CIN), vehicle group (CIN rats pretreated with vehicle), and Magnolin group (CIN rats pretreated with 1 mg/kg Magnolin). Results. The results showed that magnolin ameliorated the renal tubular necrosis, apoptosis, and the deterioration of renal function (P < 0.05). Furthermore, Magnolin reduced the renal oxidative stress, suppressed caspase-3 activity, and increased Bcl-2 expression in vivo and in vitro. Conclusion. Magnolin might protect CIN in rats through antioxidation and antiapoptosis.

The Lack of Benefit of a Combination of an Angiotensin Receptor Blocker and Calcium Channel Blocker on Contrast-Induced Nephropathy in Patients with Chronic Kidney Disease

Aim: Contrast-induced nephropathy (CIN) is a relatively common and serious complication, which occurs after the administration of contrast materials to patients. Although the pathophysiology of CIN is not exactly understood, ischemia of the medulla, oxidative stress, and direct toxicity of the contrast material are some of the factors that are implicated for the pathogenesis of CIN. To date, the only therapy that reduces the risk of CIN is volume expansion. There are conflicting results about the roles of angiotensin receptor blockers (ARB) and calcium channel blockers (CCB) in studies on CIN. For this reason the aim of this study was to compare the efficiency of the prophylactic use of amlodipine/valsartan plus hydration versus hydration only for the prevention of CIN in patients undergoing coronary angiography (CAG). Patients and methods: We prospectively enrolled 90 patients whose baseline serum creatinine levels were under 2.1 mg/dL and who were scheduled for CAG. Patients were divided into two groups. Group I (n = 45), consisted of patients who received amlodipine/valsartan plus hydration, group II (n = 45) consisted of patients who received only hydration. The patients in group I were given amlodipine/valsartan 5/160 mg once a day for a total of 3 days, starting one day before CAG and continuing on the day of and the day after the procedure. A 1 mL/kg/h sodium chloride infusion was administered for a total of 24 h, starting 12 h before the procedure and 12 h after, in all patients. The baseline serum creatinine (Scre) level was obtained before the procedure and repeated 48 h after. CIN was defined as an increase of ≥0.5 mg/dL or an increase of >25% in baseline Scre on the second day after CAG. Results: The baseline clinical characteristics of the treatment groups were similar. Baseline Scre was 1.13 ± 0.33 in group I and 1.07 ± 0.23 mg/dL in group II (p = 0.31). There was a significant difference between the Scre levels 48 h after CAG between the two groups (1.18 ± 0.33–1.05 ± 0.23) (p = 0.03). The reason for this was the increase of Scre in group I. CIN occurred in 17.8% (8/45) of patients in group I and in 6.7% (3/45) of patients in group II (p = 0.197). In the diabetic subgroup, CIN occurred in 10.5% (2/19) of patients taking amlodipine/valsartan and in none of the patients in group II (p = 0.486). The Mehran scores of the patients who developed CIN were significantly higher than those patients who did not develop CIN. Conclusion: Amlodipine/valsartan therapy plus hydration did not reduce the risk of CIN in chronic kidney disease (CKD) Stage 2 patients who underwent elective CAG using a low-osmolar nonionic contrast medium. This is because there was a decrease in the glomerular filtration rate (GFR) using the Levey Modification of Diet in Renal Disease (MDRD) formula in the amlodipine/valsartan group and CIN occurred at a higher frequency in this group; ARBs and CCBs may be withheld before CAG in high-risk patients.