Current concepts of contrast-induced nephropathy: A brief review : Journal of the Chinese Medical Association

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Review Article

Current concepts of contrast-induced nephropathy: A brief review

Chang, Chao-Fua,b; Lin, Chih-Chingb,c,*

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Journal of the Chinese Medical Association: December 2013 - Volume 76 - Issue 12 - p 673-681
doi: 10.1016/j.jcma.2013.08.011


    1. Introduction

    Contrast-induced nephropathy (CIN), also called contrast-induced acute kidney injury, is the third most common cause of hospital-acquired acute kidney injury (AKI) after impaired renal perfusion and use of nephrotoxic medications.1,2 CIN can result from intravenous or intra-arterial injections of iodine-based contrast media (CM) during enhanced X-ray and computerized tomography (CT) imaging examinations, or coronary artery interventions. It accounts for 11–12% of all cases of in-hospital AKI and is also associated with an overall in-hospital mortality rate of 6%.2,3 Among all procedures utilizing CM for diagnostic or therapeutic purposes, coronary angiography and percutaneous coronary intervention (PCI) are associated with the highest rates of CIN.2,4 An early study reported an incidence rate of CIN of about 14.5% in patients after coronary interventions, with an in-hospital mortality rate of 7.1% in those not undergoing dialysis, and 35.7% in those requiring dialysis.5 The incidence of CIN can be much higher if the patients have underlying conditions such as chronic kidney disease (CKD), diabetes, or old age.6,7 Patients with CIN are also associated with increased health resource utilization, prolonged hospital stay, increased long-term mortality, and accelerated progression of CKD.8–10

    It is possible that the incidence of CIN will increase in the future because of the continuing increase not only in the prevalence of both CKD and diabetes, but also in the number of elderly patients. Although the rates of coronary and conventional angiography have been relatively stable in recent years, the number of contrast-enhanced CT scans has risen.11 Furthermore, patients with advanced CKD are at risk of nephrogenic systemic fibrosis using gadolinium-based CM in magnetic resonance imaging examinations.12 Therefore, treatment of patients with CKD may be changed to an iodine-based CM, thereby increasing the number of patients at risk of CIN.13

    The number of published studies on CIN has dramatically increased in the past few years. Because CIN is a potentially preventable clinical condition, the more CIN is understood, the greater the likelihood of reducing the risk. The aim of this report is to provide a brief review and summary of the studies relating to CIN, especially in terms of definition, risk factors, characteristics of the CM, pathogenesis, prevention strategies, and medications.

    2. Definition and diagnosis

    CIN is defined as the acute deterioration of renal function after parenteral CM exposure in the absence of other causes. Levels of serum creatinine (Scr) usually begin to rise within 24–48 hours of CM exposure, peaking at 2–3 days and returning to baseline values within 2 weeks.14 In the related literature, CIN is usually defined as a rise in Scr of ≥0.5 mg/dL (44 mmol/L) or a 25% increase from baseline assessed within 48 hours after a radiological procedure.4,15,16 The Society of Urogenital Radiology uses the same definition, although differing in terms of Scr changes that occur within 3 days after intravascular administration of contrast without an alternative etiology.7 This definition has also been shown to consistently predict major cardiovascular events and mortality after PCI.4,10 The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines of 2012 suggest that a more specific definition of Scr concentration (increased >2×) and urine output (<0.5 mL/kg/h for >12 hours) be used for the diagnosis of CIN, as is the case for the other forms of AKI.17 However, this definition has not yet been accepted worldwide.

    A recent prospective study on the early diagnosis of CIN showed that a 5% elevation of Scr at 12 hours after CM exposure was highly predictive of CIN [sensitivity 75%, specificity 72%, odds ratio (OR) = 7.37, CI = 3.34–16.23, p < 0.001].18 Some studies have shown that serum cystatin C level and neutrophil-gelatinase-associated lipocalin (NGAL) are more specific and sensitive for the prediction of acute and early deterioration of renal function than Scr.19,20 Because cystatin C is not affected by renal tubular secretion or pharmacological treatments, serum levels of cystatin C more accurately reflect the glomerular filtration rate (GFR) than Scr, and may detect AKI 1–2 days earlier than Scr.20 However, Scr is still a better marker for detecting temporal changes of renal function in patients with CKD.21 As for NGAL, it has been shown to be useful for the earlier diagnosis of CIN, being significantly higher at 2 hours (serum NGAL) or 4 hours (urinary NGAL) after a PCI procedure.22 However, whereas the early detection and intervention using NGAL may improve renal outcomes of CIN,23 disadvantages including a lack of urine samples in patients with severe oliguria or changes in urinary concentration during volume depletion have been observed; another limitation is that NGAL cannot distinguish AKI from CKD.24

    3. Risk factors

    All patients receiving CM should be evaluated for the risk of CIN, and high-risk patients should consider pharmacological prophylaxis with therapies that are supported by clinical evidence.25 The reported risk factors are summarized in Table 1. Although many risk factors have been described for CIN, preexisting renal disease is the most important. In patients with CKD, the incidence of CIN can be relatively high and range from 14.8% to 55%, depending on the underlying conditions.16,26 By contrast, in patients with a GFR >60 mL/min, the risk of CIN is only 2%.26 Renal function should be assessed reliably by using the Cockcroft–Gault formula for creatinine clearance (CrCl) or the Modification of Diet on Renal Disease formula to estimate GFR (eGFR), instead of focusing solely on Scr.27 Prediabetes and hyperuricemia have recently been identified as risk factors for CIN, and the metabolic syndrome has been shown to increase the risk of CIN (OR = 4.26, CI = 1.19–15.25, p < 0.026).28,29 Increased systemic oxidative stress, enhanced renin–angiotensin–aldosterone system activity, and higher levels of endothelin-1 also contribute to an elevated risk of CIN. Prediabetes (serum glucose ≥124 mg/dL) has been reported to increase the incidence of CIN by 2.1-fold compared to patients with normal fasting glucose (11.4% vs. 5.5%, p = 0.032).30 And although it has been suggested that tubular obstruction by uric acid plays a role in the pathogenesis of CIN, hyperuricemia has not been shown to be an independent risk factor for CIN. Although patients with hyperuricemia in a recent study had a higher risk of CIN (OR = 4.71, p = 0.019), a high incidence of multivessel coronary involvement in hyperuricemia was linked to this association (OR = 3.59; CI = 1.12–11.48, p = 0.032). Furthermore, results from studies on the influence of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) on the incidence of CIN are conflicting.29,31,32 Because ACEI and ARB are commonly used in patients undergoing PCI, large randomized controlled trials are required to investigate their roles in the risk for CIN.

    Table 1:
    Risk factors for contrast induced nephropathy.

    In addition to GFR, many risk factors for CIN can be detected by history-taking and physical examinations. For outpatient radiological studies where Scr data are unavailable, Choyke's questionnaire or a dipstick test for urine protein can be used to identify high-risk patients.18,33 For patients undergoing PCI, Mehran's model, which includes preprocedural and periprocedural risk factors, is a simple method capable of predicting the risk of CIN.34 Mehran's model of risk factor scoring includes congestive heart failure, hypotension, use of intra-aortic balloon pumps, age >75 years, anemia, diabetes, contrast volume, and GFR, and an increased score is strongly associated with CIN [ranging from 8.4% (low-risk score) to 55.9% (high-risk score)]. Moreover, Brown's model, which includes preprocedural risk factors, has been validated for the prediction of serious renal dysfunction or the need for dialysis after PCI.35 Preprocedure Scr (37%), congestive heart failure (24%), and diabetes (15%) were found to account for 76% of the predictive ability of Brown's model, with the remaining 24% being attributable to urgent and emergent priority (10%), preprocedural intra-aortic balloon pump use (8%), age ≥80 years (5%), and female sex (1%). Although many risk factors have been identified, different studies have produced conflicting results.29 Clinical practitioners should pay attention to potentially modifiable risk factors. Whenever possible, the risk of CIN can be reduced by stopping the use of nephrotoxic drugs, improving heart function or hemodynamic status prior to examinations, using nonionic low-osmolar or iso-osmolar CM, avoiding repeat CM injections, and using a smaller volume of CM.

    4. Type and volume of CM in CIN

    4.1. Types of CM

    CM are traditionally classified according to their osmolality: high-osmolar CM (HOCM), >1500 mOsm/kg (i.e., 5–8 times plasma); low-osmolar CM (LOCM), 550–850 mOsm/kg (i.e., 2–3 times plasma); and iso-osmolar CM (IOCM), 290 mOsm/kg (i.e., isotonic to plasma).36 However, products containing different concentrations of iodine can change their osmolality and viscosity properties, which are important for the development of CIN. The characteristics of commonly used CM are listed in Table 2. Compared with HOCMs, LOCMs have a lower risk of CIN in both patients with existing renal failure (OR = 0.5, CI = 0.36–0.68) and in those without prior renal failure (OR = 0.75, CI = 0.52–1.1).37 The risk of CIN with two LOCMs, iohexol and ioxaglate, has been found to be higher than other LOCMs (e.g., iopamidol, iopramide, ioversol) and the IOCM iodixanol in many studies.27,38 Some randomized controlled trials have reported that iodixanol is not associated with a lower incidence of CIN compared with LOCMs.27,39 Other studies, by contrast, have shown that iodixanol is associated with lower rates of CIN compared with LOCMs, especially with intra-arterial administration or in patients with CKD or CKD + diabetes.40,41 Although the lower osmolality of IOCMs may decrease the incident adverse effects, the higher viscosity of IOCMs may block this protective benefit in comparison with LOCMs. To date, no consensus has been reached on the relative importance of osmolality and viscosity.42 The current guidelines of the American College of Cardiology/American Heart Association recommend the use of either IOCMs or LOCMs other than iohexol and ioxaglate in patients with CKD undergoing angiography.43

    Table 2:
    Characteristics of some contrast media.

    4.2. Volume of CM

    It is well documented that a higher volume of CM is associated with a higher risk of CIN.9 Even relatively low doses of CM (<100 mL) can result in permanent renal failure and the need for dialysis in patients with CKD,44 and each 100-mL increment in contrast volume has been shown to result in a 30% increase in the odds of CIN.45 An early study reported that the limit of the dose of radiographic contrast in patients with CKD (Scr ≥ 1.8 mg/mL) can be calculated using the following formula: 5 mL × body weight in kilograms (maximum 300 mL) ÷ Scr (mg/mL).46 Recent studies have modified the method of renal function assessment and found that the independent predictors of CIN are V/eGFR ≥ 2.39 or V/CrCl ≥ 3.7 in different populations.46,47 These findings, however, should be interpreted with care, as adverse effects may vary with the concentration and amount of the contrast agent and the technique used. In addition, elevated osmolality, volume, concentration, viscosity, and rate of administration of the solution may increase the incidence and severity of the adverse effects.48 We suggest that the CM be prewarmed to 37°C to decrease viscosity and injected with the lowest possible dose to obtain acceptable images.

    5. Pathophysiology

    The pathogenesis of CIN is still not completely understood,49 although it is clear that the root concept is medullary hypoxia-induced renal tubular damage. Whereas an interaction of various mechanisms has been shown to cause CIN,14,42 a reduction in renal perfusion and toxic effects on the tubular cells caused by direct and indirect effects of the CM on the kidneys are generally recognized as important mechanisms (Table 3).14,42,50,51

    Table 3:
    Possible mechanisms of contrast-induced nephropathy.

    5.1. Reduction in renal perfusion

    5.1.1. Rheologic alterations result in medullary hypoxia

    The viscosity of blood at 37°C is normally 3–4 × cPs. The blood flow through the vasa vecta, a major blood supply of the vulnerable deep outer renal medulla, is inversely correlated with viscosity but not osmolality. The viscosity of nonionic monomeric LOCMs at an iodine concentration of 300 mg/L is slightly higher than that of blood.14 By contrast, the viscosity of nonionic dimeric IOCMs at 37°C is much higher than that of blood. The CM can increase renal tubular viscosity when it is filtered across the glomerulus, thereby resulting in tubular obstruction and elevation of the interstitial pressure. In addition, high plasma viscosity also raises the blood resistance of the vasa vecta, thus decreasing medullary blood perfusion. Although these mechanisms result in renal medullary hypoxia and renal tubular damage (CIN), the viscosity of the fluid is not the only important factor. A higher osmolality of the CM can also diminish erythrocyte deformability, increase stiffness, and make its pass through the vasa recta more difficult.52

    5.1.2. Imbalance between oxygen demand and supply results in medullary hypoxia

    An imbalance between oxygen demand and supply also plays a role in radiocontrast-induced outer medullary hypoxic damage.53 The physiological pO2 in the renal medulla can be as low as 20 mmHg to maintain the countercurrent mechanism for controlling urine excretion.54 An early animal study observed that CM caused an initial increase in blood flow followed by 3 hours of renal vasoconstriction.55 In humans, total renal blood flow has been reported to be reduced by 50% up to 4 hours after an injection of CM in cardiac interventions.56,57 Whereas HOCMs can markedly reduce the medullary pO2 to about one-third, IOCMs can impair the medullary pO2 to a greater extent than LOCMs.58 Despite the decrease in pO2, GFR and renal medullary blood flow have been shown to be initially increased after CM exposure.53,59,60 This suggests that an increase in oxygen demand plays a role in radiocontrast-induced outer medullary hypoxic damage after CM exposure. In addition, osmotic diuresis after CM administration can also result in large amounts of NaCl having to be taken up in distal segments, thus increasing the oxygen demand in these areas.

    Complicated mechanisms work together to regulate renal blood flow and tubular function.14,50,51 Local vasoconstrictors include endothelin-A receptor, adenosine-A1 receptor, angiotensin II, vasopressin, prostaglandin E2 (PGE2) EP1, and PGE2 EP3. They are balanced by local vasodilators, such as nitric oxide, adenosine-A2 receptor, dopamine, urodilatin, endothelin-B receptor, PGE2 EP2, and PGE2 EP4. CM can induce vascular endothelial cells to release various factors that may increase vasoconstriction and decrease vasodilatation in the renal medulla and consequently cause hypoxia. Medullary hypoxia can also be aggravated by systemic effects such as a reduction in transient cardiac output, suboptimal pulmonary perfusion–ventilation, and increased hemoglobin oxygen affinity, all of which may contribute to intrarenal hypoxia.14,53,61–63

    5.2. Renal tubular damage

    5.2.1. Apoptosis

    It is not known to what extent CIN is due to direct cytotoxicity. The current understanding and knowledge of this area come mostly from studies on cells and animals. The CM, and especially ionic CM, are toxic to mesangial cells, tubular cells, and endothelial cells.64,65 The CM can decrease proximal tubular mitochondrial activity, increase production of adenosine and hypoxanthine, and impair proliferation of the cells.66,67 Regarding cellular appearance, CM can result in the concentration-dependent toxic effect of increased vacuolization.68 LOCMs and IOCMs can induce dose- and time-dependent renal cell apoptosis through a mitochondrial pathway, with an increase in caspase-3 and caspase-9 but not caspase-8 and caspase-10.69

    5.2.2. Reactive oxygen species

    Reactive oxygen species (ROS) are mainly generated by the adenosine of endothelial cells and by hypoxia of the renal medullary during CM administration.51 During oxidative stress, ROS are generated endogenously in the mitochondria. The most common ROS include oxygen radical superoxide (O2), hydrogen peroxide (H2O2), and the hydroxyl radical (OH), with O2 and OH being more reactive and permeable across cell membranes. These ROS are extracellular signaling molecules and may play roles in the effects of vasoconstriction such as angiotensin II, thromboxane A2, endothelin-1, adenosine, and norepinephrine.42 For example, O2 can rapidly scavenge nitric oxide (NO) and blunt NO activity in renal vasodilatation. N-Acetylcysteine (NAC) acts through the inhibition of the mitochondrial pathway for apoptosis.70 NAC also scavenges ROS, induces synthesis of glutathione, and possibly inhibits the angiotensin-converting enzyme.71 Although NAC that is given in addition to a hydration protocol has been recommended for the prevention of CIN in patients with mild-to-moderate renal insufficiency, this suggestion has not been universally accepted.71,72

    6. Prevention

    6.1. Evaluation of the risk of CIN and alternative imaging methods

    Because the risk of CIN can be evaluated and prevention is possible, patients at high risk should receive, where possible, alternative imaging methods without CM, as well as suitable procedural and prevention strategies (Table 4). The use of gadolinium (Gd)-based CM is not recommended to avoid nephrotoxicity in patients with renal impairment.73 The European Medicines Agency declared a contraindication for the use of gadodiamide in patients with a GFR of <30 mL/min per 1.73 m2, and issued a warning for its use in patients with a GFR between 30 mL/min and 60 mL/min per 1.73 m2. The United States Food and Drug Administration added a warning about the risk of nephrogenic systemic fibrosis following exposure to Gd-containing contrast agents in patients with a GFR of <30 mL/min per 1.73 m2 and AKI due to hepatorenal syndrome or during the perioperative liver transplantation period. When Gd-containing contrast is required to obtain optimal images, the use of low dosages of more stable macrocyclic agents is safer and preferred.74 In patients under maintenance hemodialysis, it is recommended that performing hemodialysis after CM exposure and for the following 2 days be considered.74

    Table 4:
    Strategies to prevent contrast-induced nephropathy in high-risk patients.

    6.2. Drug review

    Prior to CM exposure, use of nephrotoxic drugs including nonsteroidal anti-inflammatory drugs, COX-2 inhibitors, aminoglycoside, and cyclosporine A should be stopped for at least 2 days. Diabetic patients with preexisting renal impairment should stop metformin for 48 hours because lactic acidosis may occur once CIN develops. However, patients with normal renal function taking metformin are not at risk of CIN and should be assessed according to their overall clinical condition.75

    6.3. Nonpharmacological prevention strategies

    The CM should be prewarmed to 37°C and injected at the lowest possible dose for acceptable images. We also suggest using IOCMs or LOCMs except for ioxaglate or iohexol in all patients. In high-risk patients with CKD or CKD + diabetes requiring intra-arterial administration, iodixanol may be a better choice than LOCMs.40,41 Furthermore, clinicians should avoid repeat injections within 72 hours of the first CM administration.

    A recent pilot trial demonstrated that remote ischemic preconditioning (IPC), induced by intermittent upper-arm ischemia prior to an invasive coronary procedure, dramatically reduced the incidence of CIN in patients with CKD and those at high risk of CIN (OR = 0.21, CI = 0.07–0.57, p = 0.002).76 The IPC was accomplished by performing 4 cycles of alternating 5 minutes of inflation and 5 minutes of deflation of a standard upper-arm blood pressure cuff to the individual's systolic blood pressure plus 50 mmHg to induce transient and repetitive arm ischemia and reperfusion. The true protective mechanism of IPC is unknown, although it has been postulated that an organ releases humoral factors into the systemic circulation, which subsequently protects the remote organ. Although IPC can be applied easily and safely, a large trial is required to establish its effect.

    6.4. Pharmacological prevention strategies

    6.4.1. Volume expansion

    All patients receiving CM should have an optimal volume status at the time of exposure,25 given that volume supplementation plays an important role in the prevention of CIN. Volume expansion can decrease the activity of the renin–angiotensin–aldosterone system, reduce vasoconstrictive hormones such as endothelin, increase sodium diuresis, decrease tubule-glomerular feedback, prevent tubular obstruction and ROS production, dilute the CM in the tubular cells, and then decrease the nephrotoxic effects on the tubular cells.68 In patients without heart failure, parenteral isotonic normal saline (0.9% NaCl) without any diuretics should be started 12 hours prior to CM administration with an infusion rate of 1 mL/kg body weight per hour and continued for 24 hours. In addition, although patients should be encouraged to drink plenty of fluids (tea, mineral water, etc.), oral fluid supplementation alone is inadequate to prevent CIN. The use of sodium bicarbonate (NaHCO3) infusion may not only allow for shorter periods of volume supplementation, but can also further reduce the generation of injurious oxygen free radicals. Typically, patients should receive 154 mEq/L of NaHCO3, as a bolus of 3 mL/kg/h for 1 hour prior to CM administration, followed by an infusion of 1 mL/kg per hour for 6 hours after the procedure.77 Recent large meta-analysis studies demonstrated that NaHCO3 had a greater benefit than sodium chloride (NaCl; OR = 0.33–0.57, CI = 0.16–0.85), but no significant difference in the occurrence of death (OR = 0.6, CI = 0.26–1.41, p = 0.24) and requirement for renal replacement therapy (OR = 0.56, CI = 0.22–1.41, p = 0.22).78,79 We suggest hydration with NaHCO3 prior to CM exposure instead of NaCl for prophylaxis of CIN in patients at risk and who are not contraindicated for NaHCO3 infusion. A recent study increased the bolus concentration of NaHCO3 to 833 mEq/L with the same infusion rate, and the results indicated that this was more effective for urine alkalization and prevention of CIN.80 However, such evidence is inadequate at present to conclusively determine the optimal regimen of volume supplementation, and further studies are necessary to elucidate this issue.77–81

    6.5. N-Acetylcysteine

    NAC scavenges ROS, reduces the depletion of glutathione, and increases the effects of vasodilatation, including NO. The standard dose is 600 mg orally twice daily on the day prior to and on the day of the procedure.82 However, the many trials evaluating NAC for the prevention of CIN have yielded conflicting results.17,83–85 And even though some studies used a modified dosage, timing, or intravenous administration, the results were also inconsistent. The largest meta-analysis found that either oral or IV NAC could significantly lower the risk of CIN (OR = 0.62, CI = 0.44–0.88) when compared with NaCl hydration.83 Some studies also found that NAC could prevent CIN in a dose-dependent manner.84,85 Considering that oral NAC has a very low toxicity and low cost, it has been suggested that oral NAC at a standard dose together with parenteral hydration be used for patients at risk of CIN.17,86 In patients at very high risk of contrast-induced AKI, a combination prophylactic administration of NaHCO3 plus NAC or a real-time matched fluid replacement device are treatments still under investigation.87

    6.5.1. Other medications

    Further pharmacological prevention may be appropriate for patients who cannot tolerate parenteral hydration and are at risk of CIN. Some drugs focus on blocking vasoconstriction, increasing vasodilatation, and decreasing the ROS induced by the CM, including endothelin antagonists, adenosine antagonists (theophylline), atrial natriuretic peptide, selective dopamine A1 receptor agonist (fenoldopam), and calcium channel blockers. However, given the dearth of evidence and uncertainty of the benefits over harm, these treatments cannot be recommended at present. Moreover, most of these drugs failed to prevent CIN in high-risk patients, and some antioxidants, including ascorbic acid and statins, have also failed to show a consistent benefit in the prevention of CIN.88

    6.6. Dialysis (hemodialysis, hemofiltration, or peritoneal dialysis)

    In patients with renal failure, the renal excretion of CM is delayed. A single session of hemodialysis can effectively remove 60–90% of the CM from the blood.89 Because most CMs are middle-sized molecules, the high-flux membranes used in hemofiltration or hemodiafiltration modalities can remove the CM more quickly. However, dialysis may also cause deterioration of renal function through activation of inflammatory reactions, with the release of vasoactive substances that may induce acute hypotension.88,90 A recent meta-analysis found that dialysis did not reduce the incidence of CIN compared with routine preventive care, and that there was a trend toward a greater risk of CIN with hemodialysis.91 Subgroup analyses have found that hemodialysis was harmful for the prevention of CIN in patients with stage 3 CKD (OR = 1.53, p = 0.01), but overwhelmingly favorable over the standard treatment in reducing the risk of CIN in patients with stage 4 or stage 5 CKD (OR = 0.19, p < 0.001).86,91 However, further evidence is necessary because of the small sample sizes used in these studies. Considering the risk of dialysis procedures and the greater cost, it is recommended that hemodialysis or hemofiltration only be considered in patients with CKD stage 4 or stage 5 at high risk of CIN when functioning access is already available.88

    To date, only a few studies have evaluated the effects of CM on residual renal function in patients under maintenance peritoneal dialysis.92 It seems that intravenous CM used in the standard CT scan has no significant long-term effects on residual renal function in patients under maintenance peritoneal dialysis. Nonetheless, the aforementioned prevention strategies of CIN are still suggested unless contraindication exists. Although it takes a longer time than hemodialysis, CM can be removed effectively by peritoneal dialysis, including intermittent peritoneal dialysis, automatic peritoneal dialysis, and continuous ambulatory peritoneal dialysis.89 For this reason, peritoneal dialysis should be started immediately after CM exposure in these patients.

    6.7. Other techniques to remove CM

    One novel technique for the prevention of CIN is removing the majority of the CM from coronary sinuses prior to when it enters the systemic circulation during coronary angiography.90,93 A blood suction catheter is inserted into the coronary sinus via the right femoral vein, and venous blood from the coronary sinus is transferred into a 500-mL contrast-adsorbing column using an extracorporeal system. However, even though the mean calculated iodine removal rate has been reported at 49.4% and this new procedure has been shown to be safe and effective in reducing risk of CIN, a high technique failure rate (57%) currently limits its clinical application.88,90,93

    6.8. Electronic warning systems

    A recent paper has described a computerized alertness program in hospitalized patients that may decrease the risk of CIN (3% vs. 10%, p = 0.02).94 When contrast-enhanced CT was ordered in patients with a GFR of <60 mL/min/1.73 m, the physician was alerted by a warning message to consider prophylactic measures for CIN. Such systems should be used whenever possible.

    In conclusion, CIN is a common complication of hospital-acquired AKI and is associated with higher in-hospital mortality, prolonged hospital stay, increased long-term mortality, and accelerated progression of CKD. All patients should be evaluated for the risk factors of CIN, and the potentially modifiable risk factors should be carefully evaluated and minimized. For patients considered to be at high risk, clinicians should consider alternative imaging methods without CM where possible, and consider more suitable procedures or prevention strategies. The CM should be prewarmed to 37°C and injected at the lowest possible dose for acceptable images. IOCMs or LOCMs, except for ioxaglate or iohexol, should be used in all patients. In high-risk patients with CKD or CKD + diabetes requiring intra-arterial administration, iodixanol may be a better choice than LOCMs. Repeat injections within 72 hours of the first CM administration should be avoided. All of the drugs should be carefully reviewed, and use of nephrotoxic drugs should be stopped at least 2 days prior to the procedure. All patients receiving CM should have an optimal volume status at the time of exposure. In patients without heart failure, parenteral isotonic (0.9%) normal saline without any diuretics should be started 12 hours prior to administration of the CM. The use of bicarbonate infusion may allow for a shorter period of volume supplementation. Oral NAC together with parenteral hydration is suggested for patients at risk of CIN. Hemodialysis or hemofiltration should only be considered in patients with stage 4 or stage 5 CKD at high risk of CIN when the functioning access is already available. Electronic warning systems for physicians and technicians should be used when possible. The effects of other medications or techniques for reducing the risk of CIN remain unclear at this time, and further studies are necessary.


    This study was sponsored by a grant from the Department of Health, Taipei City Government, Taiwan, R.O.C. (96001-61-001-055).


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    contrast-induced acute kidney injury; contrast-induced nephropathy; contrast media; coronary angiography; N-acetylcysteine

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