Contrast Media-induced Nephrotoxicity Research Articles

Evaluation of two classical contrast-induced nephropathy definitions for predicting long-term mortality in patients undergoing elective percutaneous coronary intervention

Abstract Background Contrast-induced nephropathy (CIN) is a frequent complication after percutaneous coronary intervention (PCI), and is associated with poor outcome. However, the optimal definition of CIN has been debated because of its different incidence and influence on prognosis. At present, there are limited data regarding th impact of different CIN definitions on long-term mortality in patients undergoing elective PCI. Purpose To explore the influence of two classical CIN definitions on long-term mortality and identify which definition was more suitable for predicting long-term mortality in patients undergoing elective PCI.. Methods We prospectively observed 5600 consenting patients undergoing PCI from January 2012 to December 2018. Two classical CIN definitions include those defined by ESUR[Contrast-media-induced nephrotoxicity (CMN)] and AKIN[contrast induced acute kidney injury (CI-AKI)]. CMN was defined as an increase in serum creatinine (SCr) ≥25% or 0.5 mg/dLabove thebaseline level within 3 days,while CI-AKI wasdefined as an increase in SCr ≥50% or 0.3 mg/dL within 48hs after contrast medium exposure.The association of CIN with long-term mortality was investigated by Cox regression analysis.Interaction analyses were performed for long-term mortality across subgroups. Results The incidence of CIN according to ESUR (CMN) and AKIN (CI-AKI) definition were18.3% (n=1023) and 6.1% (n=342), respectively. During a median follow-up of 2 years, after adjusting other potential risk factors, multivariable cox regression analysis revealed CIN was a risk factor for long-term mortality [hazard ratio (HR): 2.021, 95% confidence interval (CI): 1.389–2.938, P<0.0001] according to AKIN definition, but not for ESUR definition (HR: 1.344, 95% CI: 0.982–1.838, P>0.05). Further interaction analysis showed that there was a significant interaction between age >75ys and CMN for long-term mortality (P=0.042) while no such association was observed between age >75ys and CI-AKI (P=0.806). Conclusions CIN defined by AKIN may be more suitable for predicting long-term mortality in patients undergoing elective PCI. However, in elderly patients, CIN defined by ESUR could also be used for predicting long-term mortality. Association Between CIN and mortality Funding Acknowledgement Type of funding source: None

Protective Effect of Ginger Extract against Contrast media-Induced Nephrotoxicity in Rats.

Background: Nephrotoxicity was reported in the initial clinical trials of contrast media. Aim of study: Our study was designed to evaluate the protective effect of ginger extract against nephrotoxicity induced by contrast agent. Material & Methods: Animals were divided into 5 groups as follow: Group1 (Control): They were not received any treatment during experiment period. Group2 (Ginger): Animals were deprived from water for 72 hours , then orally administrated with 400 mg/Kg/day of ginger extract for 72 hours. Group3 (protective): Animals were pre administrated orally with ginger extract with 400 mg/Kg for one week, then rats were deprived of water for 72 hours, then urografin was induced by a single (I.V.) at dose of 10mL per kg after that animals were orally administrated with 400 mg/Kg/day of ginger extract for 3 consecutive days. Group 4 (positive)(contrast media): Animals were induced by a single intravenous (I.V.) of urografin at dose of 10mL per kg after deprivation of water for 72 hours. Group 5(therapeutic): Animals rats were deprived of water for 72 hours, then Contrast-induced nephrotoxicity was induced (as group 4) , after that animals were post administrated with ginger extract 400 mg/Kg (for 3 days). Results: Administration contrast media caused significant elevation in serum urea, creatinine concentration, kidney tissue levels of MDA and NO. Also it caused significant increase in Cystain C , NGAL and TNFα levels. Also it significantly decreased SOD activity and GSH level. Treatment with Ginger extract restored the elevation of concentration of urea and creatinine, also oxidative stress markers in groups 3 and 5 and decreased Cystain C , NGAL and TNFα levels. Histopathological analysis confirmed that. Conclusion: ginger extract have a protective role in contrast media induced nephrotoxicity.

The preventive effect of Berberis vulgaris extract on contrastinduced acute kidney injury

Background: Oxygen free radicals are known as one of the causes of kidney injury. Therefore, Berberis vulgaris which has high level of antioxidant activity may be able to prevent this injury by elimination of free radicals. Objectives: This study was aimed to investigate the protective effect of B. vulgaris extract on contrast media-induced nephrotoxicity. Materials and Methods: To conduct this experimental study, 30 male rats were randomized to three groups; Control, contrast media, and contrast media + B. vulgaris extract. After the treatment, histopathological damages to the kidney tissues were comparatively studied. Results: Tissue damage was greater in the contrast media-treated group than the other two groups (P < 0.001). In group treated with B. vulgaris extract, the rate of tissue damage deceased significantly (P < 0.001). Conclusions: This study showed the positive effects of B. vulgaris on contrast media-induced nephrotoxicity. This inexpensive and non-toxic medicinal plant might be used as an effective agent for people at risk of contrast-induced acute kidney injury (CI-AKI).

Did low tube voltage CT combined with low contrast media burden protocols accomplish the goal of "double low" for patients? An overview of applications in vessels and abdominal parenchymal organs over the past 5years.

Imaging communities have already reached a consensus that the radiation dose of computed tomography (CT) should be reduced as much as reasonably achievable to lower population risks. Increasing attention is being paid to iodinated contrast media (CM) induced nephrotoxicity (CIN); a decrease in the intake of iodinated CM is required by increasingly more radiologists. Theoretically, the radiation dose varies with the tube current time and square of the tube voltage, with higher iodine contrast at low photon energies (Huda etal. [2000] Radiology, 21 7, 430-435).The use of low tube voltage is a promising strategy to reduce both the radiation dose and CM burden. The term 'double low' has been coined to describe scanning protocols that reduce radiation dose and iodine intake synchronously. These protocols are becoming increasingly popular in the clinical setting. The aim of this review was to describe all original studies using the 'double low' strategy in the last 5years. We searched an online electronic database (PubMed) from January 2011 to December 2015 for original studies published on the relationship of low tube voltage with low radiation dose and low iodine contrast media burden in patients undergoing CT scans. Studies that failed to reduce radiation dose or iodine CM burden were excluded in this study. Thirty-seven studies aimed at reducing radiation dose using low tube voltage combined with iodine CM reduced protocols were included in this study. Most studies evaluated conditions associated with arteries. Four were cerebral and neck computed tomography angiography (CTA) studies, 15 were pulmonary CTA (pCTA) and coronary CTA (cCTA) studies, one concerned myocardial perfusion, five studies focused on the thoracic and abdominal aorta, and one investigated renal arteries. Three studies consisted of CT venography (CTV) of the pelvis and lower extremities. Six publications examined the liver, and two focused on the kidney. Overall, this review demonstrates that the low tube voltage CT protocol is a powerful tool to reduce the radiation dose in CTA, especially with pCTA and cCTA.

Preventing contrast media-induced nephrotoxicity

Preventing contrast media-induced nephrotoxicity

Effects of hypercholesterolemia on contrast media-induced nephrotoxicity in rats

To explore the effects of short- and long-term dietary hypercholesterolemia on contrast media-induced nephrotoxicity in rats. The male Wistar rats were fed either a normal rodent diet or a high cholesterol diet. At the end of 2 and 8 weeks, 8 rats from each group received a tail vein injection of either Iohexol injection (groups NC and HC) or vehicle (groups N and H). Blood lipid, renal function, renal hemodynamics, renal and urinary prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), renal nitric oxide and malondialdehyde (MDA) were determined at Day 1 following the administration of contrast media. The dosing of contrast media induced obviously increased serum creatinine compared with normal rats ((185 ± 28) vs (53 ± 3) µmol/L, P < 0.01) and severe renal tubular necrosis in rats with a high cholesterol diet for 8 weeks but did not in normal-diet rats or rats with a high cholesterol diet for 2 weeks. The renal and urinary levels of PGE2 and TXB2 increased significantly in rats of groups H and HC at the end of 8 weeks. The renal production of nitric oxide decreased while the concentration of MDA increased markedly in groups HC and H at the end of 8 weeks. Long-term hypercholesterolemia appears to be a risk factor of contrast media-induced acute renal failure. And it may be associated with the disorder of intrarenal prostaglandins and the abnormality of renal nitric oxide system as induced by lipid peroxidation.

Effects of Short- and Long-Term Hypercholesterolemia on Contrast-Induced Acute Kidney Injury

Background: Whether hypercholesterolemia is a risk factor for contrast-induced acute kidney injury (CI-AKI) remains unclear. In the present study, the effects of short- and long-term dietary hypercholesterolemia on contrast media-induced nephrotoxicity were evaluated. Methods: Rats were fed either a normal rodent diet (N) or high-cholesterol diet (H). At the end of 2 and 8 weeks, 8 rats from each diet group were given a tail vein injection of either iohexol (group NC and group HC) or vehicle (group N and group H). Blood lipids, renal function and renal hemodynamics were evaluated 1 day after contrast media administration. Renal and urinary prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) were detected by radioimmunoassay. Renal nitric oxide and malondialdehyde (MDA) were measured by the Griess reaction and thiobarbituric acid method, respectively. Results: Contrast media administration increased serum creatinine levels and induced severe renal tubular necrosis in rats fed the high-cholesterol diet for 8 weeks but not in rats fed the normal diet or high-cholesterol diet for 2 weeks. The renal and urinary PGE₂ and TXB₂ levels increased significantly in rats in group H and group HC at the end of 8 weeks. Renal nitric oxide production decreased, and MDA levels increased markedly in group HC and group H at the end of 8 weeks. Conclusions: We conclude that long-term hypercholesterolemia appeared to be a risk factor for CI-AKI, which might be associated with disorders in intrarenal prostaglandins and abnormalities in renal nitric oxide system induced by lipid peroxidation.

Arterial imaging in patients with lower extremity ischemia and diabetes mellitus

Precise, comprehensive imaging of the arterial circulation is the cornerstone of successful revascularization of the ischemic extremity in patients with diabetes mellitus. Arterial imaging is challenging in these patients because the disease is often multisegmental with a predilection for the distal tibial and peroneal arteries. Occlusive lesions and the arterial wall itself are often calcified and patients presenting with ischemic complications frequently have underlying renal insufficiency. Intra-arterial digital subtraction angiography (DSA), contrast enhanced magnetic resonance angiography (MRA), and more recently, computerized tomographic angiography (CTA) have been used as imaging modalities in lower extremity ischemia. Each has specific advantages and shortcomings in this patient population, which will be summarized and contrasted in this review. DSA is an invasive technique most often performed from a femoral arterial puncture and requires the injection of arterial contrast, which can occasionally cause allergic reactions. In patients with pre-existing renal insufficiency, contrast infusion can result in worsening renal failure; although usually self-limited, it may occasionally require hemodialysis, especially in patients with diabetes. However, DSA provides the highest degree of spatial resolution and image quality. It is also the only modality in which the diagnosis and treatment of arterial disease can be performed simultaneously. MRA is noninvasive, and when enhanced with gadolinium contrast injection provides arterial images of comparable quality to DSA and in some circumstances may uncover distal arterial targets not visualized on DSA. However, spatial resolution is inferior to DSA and erroneous interpretations due to acquisition artifacts are common. Specialized equipment and imaging techniques are necessary to minimize their occurrence in the distal lower extremity. In addition, due to the risk of inducing nephrogenic systemic fibrosis, gadolinium-enhanced MRA cannot be used in patients with renal insufficiency. CTA is noninvasive and rapidly performed, with better spatial resolution than MRA, but requires the largest volume of contrast infusion, exposes patients to high-doses of radiation, and is subject to interpretive error due to reconstruction artifacts especially in heavily calcified arteries, limiting its usefulness in many patients with diabetes. For patients in whom the planned intervention is a surgical bypass, DSA and MRA will provide high quality images of the lower extremity arterial anatomy. For patients in whom a catheter-based intervention is the likely treatment, a diagnostic DSA immediately followed by a catheter-based treatment in the same procedure is the preferred approach. In patients with pre-existing renal dysfunction, in which gadolinium-enhanced MRA is contraindicated, DSA or CTA can be performed. However, patients should have an infusion of intravenous normal saline solution or sodium bicarbonate before the procedure to reduce the incidence of contrast-induced nephropathy.

Metformin-associated lactic acidosis following contrast media-induced nephrotoxicity

Metformin-associated lactic acidosis following contrast media-induced nephrotoxicity V. Jain;D. Sharma;H. Prabhakar;H. Dash; European Journal of Anaesthesiology

Effects of Acetylcysteine and Probucol on Contrast Medium-induced Depression of Intrinsic Renal Glutathione Peroxidase Activity in Diabetic Rats

Antioxidants such as N-acetylcysteine and probucol have been used to protect patients from contrast media-induced nephrotoxicity. The mechanisms underlying these protective effects are not well understood. We hypothesized that acetylcysteine and probucol alter the activity of endogenous antioxidant enzyme activity. Four weeks after induction of diabetes with streptozotocin, diabetic and nondiabetic rats were divided into three groups. Group 1 rats did not receive any antioxidant agents. Group 2 rats were treated with acetylcysteine and group 3 rats with probucol for 1 week before injection of the contrast medium diatrizoate (DTZ). We found that diabetic rats had higher renal glutathione peroxidase (GPx) activity than normal rats. DTZ suppressed renal GPx activity significantly in both group 1 diabetic and normal rats. Interestingly, renal GPx activity in both diabetic and normal rats pretreated with acetylcysteine or probucol was not inhibited by DTZ. Renal superoxide dismutase (SOD) increased significantly in normal rats after DTZ injection, but not in diabetic rats. Finally, acetylcysteine or probucol did not significantly influence renal SOD. These findings suggest that the renal protective effects of acetylcysteine and probucol against contrast-induced oxidative stress and nephrotoxicity may be mediated by altering endogenous GPx activity.

Produits de contraste en cardiologie interventionnelle coronaire

Contrast media are widely used for percutaneous coronary interventions. Currently, about a dozen types of contrast media are available in France. On account of their overall safety, only low osmolar and isosmolar contrast media are used in practice. However, the appropriate use of contrast media remains difficult as accurate recommendations are lacking. Several doubts are still present regarding potential adverse effects of contrast media. Our review summarizes contrast media-related risks (hypersensitivity, arrhythmic risk, effects on coagulation and platelets, contrast media-induced nephrotoxicity) underlying mechanisms, prophylaxis strategies, and differences among contrast media. Many questions remain in this area and we need further prospective randomised trials.

Renal complications associated with contrast media

The use of iodinated contrast media (CM) is associated with a risk of renal insufficiency. However, the definition of renal insufficiency varies. Contrast media impair the renal medullary flow and exert a direct toxic effect on renal tubular cells. The ensuing renal insufficiency results from haemodynamic disturbances and tubular cell injury. Under normal conditions, the renal medulla—in which the loop of Henle and the vasa recta follow a deep, ‘hairpin’-like course and achieve urinary concentration/ dilution—is a region of low blood flow and low pO2. Extracellular volume depletion contributes to further reduce blood flow to the deeper portion of the outer medulla. Contrast media markedly diminish renal medulla perfusion and oxygenation. The thick ascending limb (TAL) of the loop of Henle is particularly affected by hypoxic stress. Contrast media-induced nephrotoxicity (CIN) stems from a combination of erythrocyte sludge in the vasa recta, renal vasoconstriction and toxicity to tubular epithelial cells, especially in the TAL. Ageing, dehydration and chronic renal insufficiency, especially diabetic nephropathy, are three conditions under which CM most commonly induce renal insufficiency, with an increased risk in the case of concomitant treatment with nephrotoxic medications. The prevention of CIN follows from these intricate pathophysiological mechanisms. It is based on reducing CM osmolality, opposing medullary vasoconstriction and hypoxic stress with pharmacological agents and, above all, increasing the renal medullary flow by intravenous infusion of saline.

Effects of contrast media on renal function in patients with cirrhosis: a prospective study.

Patients with cirrhosis are frequently submitted to radiological procedures that require the administration of contrast media. Contrast media is a well-known cause of renal failure, particularly in the presence of some predisposing conditions. However, it is not known whether cirrhosis constitutes a risk factor for contrast media-induced renal failure. The aim of this study was to assess the possible nephrotoxicity of contrast media in patients with cirrhosis. In a first protocol, renal function was evaluated with sensitive methods (glomerular filtration rate using iothalamate I 125 clearance and renal plasma flow using iodohippurate I 131 clearance) before and 48 hours after the administration of contrast media in 31 patients with cirrhosis (20 with ascites, 5 with renal failure). Solute-free water clearance, urine sodium, prostaglandins, and markers of tubular damage were also measured. The administration of contrast media was not associated with significant changes in renal function tests, neither in the whole group of patients nor in patients with ascites or renal failure. Urinary prostaglandin E2 and N-acetyl-beta-D-glucosaminidase increased significantly, but sodium and solute-free water excretion remained unchanged. In a second protocol, a different series of 60 patients with cirrhosis and renal failure were examined prospectively. No patient had renal failure due to contrast media. Only in 1 patient with septic shock was contrast media a possible contributing factor. In conclusion, the administration of contrast media is not associated with adverse effects on renal function in patients with cirrhosis. Cirrhosis does not appear to be a risk factor for the development of contrast media-induced nephrotoxicity.

Biochemical evidence of contrast media-induced nephrotoxicity

Biochemical evidence of contrast media-induced nephrotoxicity

Contrast media-induced nephrotoxicity--questions and answers.

The intravascular administration of contrast media (CM) can produce acute haemodynamic changes in the kidney characterized by an increase in renal vascular resistance and a decrease in the glomerular filtration rate (GFR). These changes may lead to clinically significant reduction in renal function in patients with pre-existing risk factors such as diabetic nephropathy, congestive heart failure and dehydration. The pathophysiology of the renal haemodynamic effects of CM involves activation of the tubuloglomerular feedback (TGF) mechanism and the modulation of the intrarenal production of vasoactive mediators such as prostaglandins, nitric oxide, endothelin and adenosine. The TGF response is osmolality-dependent and accounts for about 50% of the acute functional effects of high osmolar CM on the kidney. Reduction in the synthesis of the endogenous vasodilators nitric oxide and prostaglandins increases the nephrotoxicity of CM. Endothelin and adenosine play a crucial role in mediating the acute functional effects of CM. Antagonists of these mediators attenuate the reduction in renal function induced by contrast agents. Vacuolization of the cells of the proximal tubules and necrosis of those of the medullary ascending limbs of loops of Henle are the main structural effects of CM in the kidney. The reduction in renal function induced by CM could be minimized by the use of low osmolar CM and adequate hydration. The prophylactic administration of calcium channel blockers and adenosine antagonists such as theophylline may also offer some protective effect.

Role of intracellular calcium stores in contrast medium-induced renal vasoconstriction.

Renovascular smooth muscle contractility, an important factor in contrast media-induced nephrotoxicity, depends on intracellular Ca2+ concentration, which is composed of extracellular Ca2+ influx and intracellular Ca2+ release. These factors were investigated in contrast media-induced renal vasoconstriction in an in vitro model. KCl-induced isometric contractions of rabbit renal artery were compared with contractions elicited by contrast media (diatrizoate, iohexol, iopamidol). Measurements were made after incubation with the Ca2+ channel blockers nifedipine, verapamil, and diltiazem to assess the role of extracellular Ca2+ influx and after ryanodine and thapsigargin to investigate the role of intracellular Ca2+ release. The Ca2+ channel blockers partially inhibited contractions induced by contrast media, while KCl-induced contractions were completely abolished. Ryanodine and thapsigargin also markedly inhibited contrast media-induced contractions. Ionic and nonionic contrast media induced quantitatively different renal vasocontractions. Ca2+ channel blockers inhibited this vasocontraction only slightly compared with intracellular Ca2+ release blockers.

Bosentan, an orally active endothelin antagonist: effect on the renal response to contrast media.

To examine the effect of bosentan, an orally active endothelin-receptor antagonist, on the renal response to contrast media in the isolated perfused rat kidney (IPRK) and to establish whether bosentan can inhibit contrast media-induced nephrotoxicity in a multiple-insult model in the conscious rat. Renal function was measured in the IPRK (n = 24) and in the rats that had undergone unilateral nephrectomy, were maintained on a salt-free diet, and were receiving indomethacin (10 mg/kg/d; n = 60). In the IPRK, diatrizoate and iotrolan reduced the glomerular filtration rate and renal perfusate flow, an effect markedly inhibited by bosentan (n = 6 per group). In the multiple-insult rat model, the fall in creatinine clearance produced by diatrizoate was also markedly inhibited by bosentan (n = 15 per group). Endothelin antagonists such as bosentan may be used to reduce the prevalence of contrast-induced nephrotoxicity.

Risk for contrast media-induced nephrotoxicity was low for both high and low-contrast media

Risk for contrast media-induced nephrotoxicity was low for both high and low-contrast media

Contrast media-induced nephrotoxicity: an overview

Contrast media-induced nephrotoxicity: an overview

Contrast media-induced nephrotoxicity. Survey and present state.

Reports of renal failure induced by contrast media are increasing. Adverse effects of contrast media on kidney function include diuresis, changes in renal blood flow, osmotic nephroses, albuminuria, enzymuria and, most important, glomerular filtration rate. Animal studies indicate that the new nonionic contrast medium, iohexol, has fewer adverse effects on kidney function than the ionic media currently used. Three clinical studies offer some evidence of the effect of iohexol on renal function, but it is not yet possible to conclude that lower nephrotoxicity found in animals will also be found in man. Further clinical studies are warranted, and careful monitoring of contrast media clearance is recommended in all high-risk patients.