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Pharmacological strategies to prevent contrast-induced acute kidney injury.

1. Introduction

Contrast-induced acute kidney injury (CI-AKI) is the most common iatrogenic cause of acute kidney injury (AKI) after intravenous contrast media administration, with an incidence occurring from 1 to 25% [1-4]. CI-AKI has been defined as the acute deterioration of renal function after contrast media administration in the absence of other causes [5]. Unfortunately, the definition of CI-AKI has not been reliable in the literature, which makes the data comparison from various complex studies. In general, CI-AKI was defined as an increase in serum creatinine (SCr) concentration of 0.5mg/dL or 25% above baseline within 48 h after contrast administration [6-10]. Impairment of renal function in CIAKI occurs within 3 days after intravenous contrast media administration, while the peak of SCr is observed at 3 to 5 days and returns to the baseline value within 1 to 3 weeks [11,12]. The incidence of CI-AKI is low (1 to 2%) in patients with normal renal function [1] but increases as high as 25% in high risk patients especially with chronic kidney disease (CKD) or diabetes mellitus with CKD [2,13]. In addition, old age, higher volume of contrast agent used, congestive heart failure, hypotension, anemia, use of nephrotoxic drug, and volume depletion have been associated with increased risk of CI-AKI [14-16]. Consequently, CI-AKI, particularly in high risk patients, contributes to extended hospitalizations and increases long-term morbidity and mortality [17-19].

Development of CI-AKI involves at least three complementary pathophysiological processes. First, contrast agents induce renal vasoconstriction, accompanied by shunting of blood flow from the medulla to the cortex, a consequence of reducing renal blood flow to the medulla which is followed by renal medulla ischemia [20]. Second, hypoxia can promote further ischemic renal injury by the increase of oxygen free radicals through oxidative stress [21]. Organ injury occurs when tissue hypoperfusion generates reactive oxygen species (ROS) that exceed the patient's antioxidant reserves [22]. Finally, contrast agent is direct tubular toxicity, leading to mitochondrial dysfunction, generation of ROS, and program cell death [6, 22, 23].

In fact, there is no effective therapy once AKI has turned on. Thus, preventive approach should be the best option for all patients with risk to avoid CI-AKI. Several strategies to prevent CI-AKI have been tested in animal models and clinical trials. The rationale for the prevention of CI-AKI by periprocedural intravascular volume expansion is through blocking its two complementary pathophysiological processes [24]. First, expansion of the intravascular space is thought to blunt the vasoconstrictive effect of contrast on the renal medulla. Second, intravascular fluids are believed to attenuate the direct toxic effect of contrast agents on tubular epithelial cells. Hence, intravascular volume expansion with isotonic saline and using of iso-osmolar contrast agents have provided more consistent positive results and were recommended in the prevention of CI-AKI [25,26]. However, the proportion of patients with risk still develops CI-AKI.

Several pharmacologic agents have been evaluated for the prevention of CI-AKI. The mechanisms of pharmacological prophylaxis for CI-AKI include vasodilator; antioxidant agents have been implicated in the pathogenesis of CI-AKI. This review discusses the current pharmacological strategies to prevent CI-AKI in patients with the risk of developing CI-AKI.

2. Pharmacological Strategies to Prevent CI-AKI

2.1. Intravascular Volume Expansion for CI-AKI Prevention. The intravascular volume expansion was believed to prevent the adverse effect of contrast media administration by 2 distinct mechanisms: (1) reducing the vasoconstrictive effect of contrast media on renal medulla by suppression of vasopressin secretion, inhibition of renin-angiotensin-aldosterone system, and increase of prostaglandin synthesis, and (2) attenuating the direct toxic effect of contrast media on renal tubular epithelial cells by decreasing proximal tubular salt and water reabsorption which results in diluting the intratubular fluid and reducing the intratubular viscosity [24]. In animal model, the sodium-replete dogs had less magnitude and duration of vasoconstrictive response after contrast media administration than sodium-deplete dogs [27]. A reduction of glomerular filtration rate, renal plasma flow, and alteration of the antioxidant enzyme activity after contrast media administration occurred only in water-depleted rats but not in water-replete rats [28, 29].

The first clinical trial for intravascular volume expansion to prevent CI-AKI was presented in 1994. Solomon et al. [30] randomized 78 patients with CKD who underwent coronary angiography to receive intravenous 0.45% saline alone, for 12 h before and 12 h after the procedure, or in a combination with mannitol or furosemide. The incidence of CI-AKI occurred 11% in 0.45% saline group, 28% in 0.45% saline plus mannitol group, and 40% in 0.45% saline plus furosemide group (P = 0.02 for the comparison with the 0.45% saline group). However, the efficacy of intravenous volume expansion to prevent CI-AKI was inconclusive because there was no control or nonsaline infusion group in this study. In addition, the most suitable route of fluid administration and the type of fluid was doubtful.

2.2. Oral Fluid versus Intravenous Fluid for CI-AKI Prophylaxis. There are several trials studied on the effects of route of fluid administration on CI-AKI prophylaxis. Taylor et al. [31] randomized 36 patients with CKD who underwent cardiac catheterization to receive intravenous 0.45% saline at a rate of 75 mL/h for 12 h before and 12 h after the procedure or oral hydration at a rate of 1,000 mL over 10 h before the procedure plus intravenous 0.45% saline at a rate of 300 mL/h beginning just before and 6 h after the procedure. The incidences of CI-AKI were not different between intravenous alone and intravenous plus oral fluid group, 6 and 11%, respectively. Trivedi et al. [32] randomized the patients who underwent nonemergency cardiac catheterization to receive intravenous 0.9% saline at a rate of 1 mL/kg/h for 12 h before and 12 h after the procedure or unrestricted oral fluid. The incidences of CIAKI were significantly higher in intravenous fluid group than in unrestricted oral fluid group, 3.7 and 34.6%, respectively (P = 0.005). Dussol et al. [33] randomized 312 patients with CKD who underwent various radiological procedures which required contrast media into 4 groups to receive (1) oral NaCl 1 g per 10 Kg for 2 days before the procedure, (2) intravenous 0.9% saline at a rate of 15 mL/kg/h for 6h before the procedure, (3) intravenous 0.9% saline at a rate of 15 mL/kg/h for 6 h before the procedure plus theophylline 5 mg/kg 1 h before the procedure, or (4) intravenous 0.9% saline at a rate of 15 mL/kg/h for 6 h before the procedure plus furosemide 3 mg/kg after the procedure. The incidences of CI-AKI were not significantly different between the 4 groups: 6.6, 5.2, 7.5, and 15.2% in groups 1 to 4, respectively. Cho et al. [34] randomized 91 patients with CKD who underwent cardiac catheterization into 4 groups to receive (1) intravenous 0.9% saline 3mL/kg over 1h just before and at a rate of 1 mL/kg/h for 6 h after the procedure, (2) intravenous isotonic NaHC[O.sub.3] 3mL/kg over 1h just before and at a rate of 1 mL/kg/h for 6 h after the procedure, (3) oral water 500 mL in 2 h which begin 4 h before and 600 mL after the procedure, (4) oral water 500 mL in 2h which begin 4h before the procedure with oral NaHC[O.sub.3] 46.4 mEq 20 min before the procedure, and (5) 600 mL of oral water after the procedure with oral NaHC[O.sub.3] 30.4 mEq at 2 and 4 h after the initial dose. The incidences of CI-AKI were not significantly different between the 4 groups: 22,10, 5, and 5% in groups 1 to 4, respectively. According to these conflicting results, the appropriate route of fluid administration remains inconclusive.

2.3. Isotonic Fluid versus Hypotonic Fluid for CI-AKI Prophylaxis. Mueller et al. [25] conducted a study to compare the efficacy of intravenous 0.45% NaCl and 0.9% NaCl for CI-AKI prophylaxis. 1,620 patients who underwent coronary angiography were randomized to receive 0.9% saline or 0.45% saline plus 5% glucose at a rate of 1 mL/kg/h beginning at 8 AM on the day of procedure until 8 AM on the next morning. The incidences of CI-AKI were significantly lower in isotonic saline group than in half-isotonic saline group: 0.7 and 2.0%, respectively (P = 0.04). On subgroup analysis, the patients with diabetes received radiocontrast [greater than or equal to] 250 mL and particularly female patients had benefit from the isotonic fluid therapy.

2.4. Sodium Chloride versus Sodium Bicarbonate for CI-AKI Prophylaxis. The administration of intravenous fluid that contains sodium bicarbonate can cause an alkalinization of the intratubular fluid and result in reduction of injurious hydroxyl radicals, which, theoretically, might be more beneficial than sodium chloride fluid therapy in CI-AKI prophylaxis. Merten et al. [35] randomized 119 patients with SCr [greater than or equal to] 1.1mg/dL who underwent radiographic procedure requiring contrast media to receive isotonic saline or sodium bicarbonate at a similar rate of 3 mL/kg/h for 1 h before and 1mL/hg/h for 6h after the procedure. The incidences of CIAKI were significantly higher in sodium chloride group than in sodium bicarbonate group: 13.6 and 1.7%, respectively (P = 0.02). Briguori et al. randomized 366 patients with CKD who underwent coronary and/or peripheral angiography into 3 groups to receive intravenous (1) 0.9% saline with NAC, (2) sodium bicarbonate with NAC, and (3) 0.9% saline with ascorbic acid and NAC. The incidences of CI-AKI were significantly lower in sodium bicarbonate with NAC group: 9.9, 1.9, and 10.3% in groups 1 to 3, respectively (P = 0.019). Recio-Mayoral et al. [36] randomized 111 patients with acute coronary syndrome who underwent emergency percutaneous coronary intervention to receive sodium bicarbonate with NAC or 0.9% saline with NAC. The incidences of CIAKI were significantly lower in sodium bicarbonate with NAC than in 0.9% saline with NAC group: 1.8 and 21.8%, respectively (P < 0.001).

2.5. Meta-Analysis Comparing the Efficacy of Sodium Chloride with Sodium Bicarbonate for CI-AKI Prophylaxis. Data from several meta-analyses of the efficacy of sodium chloride versus sodium bicarbonate for CI-AKI prophylaxis are summarized in Table 1. Six out of six meta-analyses [37-42] demonstrated that volume expansion therapy with sodium bicarbonate is superior to sodium chloride in preventing CI-AKI. However, the efficacy of sodium bicarbonate and sodium chloride was not significantly different in meta-analyses from 14 unpublished studies by Zoungas et al. [41] (RR = 0.78, 95% confidence interval 0.52-1.17; P = 0.05). The inconsistent data between published and unpublished studies should be cautiously considered in the use of this treatment for CI-AKI prophylaxis until more reliable evidence from large-scale clinical studies is available.

In summary, although the most efficacious route for volume expansion in CI-AKI prophylaxis remains debatable, the intravenous route is more reliable for fluid delivery to the patients. Thus, we suggested using the intravenous route if it is available for CI-AKI prophylaxis. The CIAKI prevention with isotonic saline is more effective than hypotonic saline. And according to the available data, the volume expansion with saline is at least as effective as sodium bicarbonate for CI-AKI prophylaxis. Thus, we suggested using intravenous/isotonic saline or sodium bicarbonate for volume expansion in CI-AKI prophylaxis depending on the patient's condition.

2.6. N-Acetylcysteine (NAC) for CI-AKI Prevention. The possible role of reactive oxygen radicals in the pathogenesis of CI-AKI led to the evaluation of NAC as an antioxidant. The antioxidant effect of NAC relates to both direct free radical scavenging activity and capability to enhance glutathione synthesis [43]. In experimental study, the administration of contrast media results in augmentation of lipid peroxidation marker, reduction of glomerular filtration rate (GFR), and deterioration of tubular structures. In contrast, pretreatment of animals with antioxidants diminishes the hazardous effect of contrast media, including NAC that attenuates the adverse renal effect from contrast media [28, 44-46].

The clinical trials comparing NAC and placebo for prophylaxis of CI-AKI after angiography are shown in Table 2. The first clinical trial for NAC in the prevention of CIAKI was reported by Tepel et al. [47] in 2000. In this prospective study, 83 patients with CKD who underwent computed tomography (CT) with intravenous contrast media were randomized to receive 600 mg of oral NAC or placebo twice daily for 2 days. All patients received intravenous 0.45% NaCl at a rate of 1mL/kgBW/h for 12 h before and 12 h after administration of the contrast media. The CI-AKI occurred in 2% of the NAC group compared to 21% in the placebo group (P = 0.01). In2002, Shyu et al. [48] prospectively randomized 121 patients with CKD who underwent a coronary procedure with standard intravascular volume expansion protocol to receive oral NAC or placebo. The CI-AKI occurred in 3.3% in the NAC group, and 24.6% in placebo group (P < 0.001). Similarly, the prospective study published by Kay et al. [49] in 2003 demonstrated a significantly lower incidence of CIAKI in the patients with CKD undergoing elective coronary intervention who receive oral NAC (4%), compared to the placebo group (12%) (P = 0.03).

In contrast, several studies failed to demonstrate the benefit of NAC in the prevention of CI-AKI. Webb et al. [50] prospectively randomized 487 CKD patients who underwent cardiac catheterization to receive a single dose of intravenous NAC 500 mg or placebo within 1 h before the administration of contrast media. All patients received 200 mL of intravenous 0.9% NaCl before the procedure, followed by 1.5 mL/kgBW/h for 6 h or until discharge. The incidences of CI-AKI in both groups were similar: 23.3% and 20.7% in NAC and placebo groups, respectively (P = 0.57). In 2011, the largest trial of NAC for the prevention of CI-AKI was published by ACT investigators [3]. The 2,308 patients with one or more risk factors for CI-AKI undergoing coronary or peripheral arterial angiography were randomized to receive 4 doses of 600 mg oral NAC or placebo twice daily. All patients received 0.9% NaCl at a rate of 1mL/kgBW/h from 6 to 12 h before and 6 to 12 h after procedure. The incidences of CI-AKI were similar, 12.7% in both groups (P = 1.00).

2.7. Systematic Review and Meta-Analysis of the Efficacy of NAC for CI-AKI Prophylaxis. Data from several meta-analyses of the efficacy of NAC for CI-AKI prophylaxis are summarized in Table 3. To date, at least nine out of the 16 meta-analyses have showed beneficial of NAC treatment effect in reducing the incidence of CI-AKI compared to placebo [51-59]. However, disparate results are shown in the remaining studies [3, 60-65]. Various factors may contribute to these inconsistent efficacies of NAC in CI-AKI prophylaxis, including definition of CI-AKI, baseline risk factors, timing and route of NAC administration, dosage of NAC, amount and type of intravenous hydration protocols, volume, type, and route of administration of contrast media, type of performed procedures, and methodological characteristics of trials. In 2008, Kelly et al. [58] conducted a meta-analysis that included 41 studies with a sample size of 3,393 patients. Their results suggested that oral or IV NAC significantly lowered the risk of CI-AKI when compared with intravascular volume expansion with saline alone (relative risk (RR): 0.62, 95% CI: 0.44-0.88). In 2011, ACT investigators [3] encompassed 46 randomized controlled trials comparing NAC with placebo in patients undergoing cardiac or peripheral angiography. The investigators showed that NAC does not reduce the risk of CIAKI or other clinically relevant outcomes in at risk patients (RR: 1.00, 95% CI: 0.81-1.25; P = 0.97).

In summary, the data regarding the efficacy of NAC in CI-AKI prophylaxis remain controversial. However, due to very low toxicity, low cost, and potential benefit of NAC, this medication remains commonly used for the prophylaxis of CI-AKI. We recommend the use of oral NAC at a dose of 600 mg twice daily on the day before and day of the procedure to patients at risk of CI-AKI.

2.8. Statins for CI-AKI Prevention. Statins also have the pleiotropic effect, as an anti-inflammatory effect and antioxidant, besides the main inhibitory effect on hydroxymethyl-glutaryl coenzyme A reductase. In vitro, statins exerted the production of heme oxygenase-1 protein, interfered with NADPH oxidase activity, diminished adhesion molecule expression, and reduced the free radical formation [66-68]. Pretreatment of rats with statin appeared to attenuate the SCr level elevation and lessened the unfavorable histological findings in ischemic reperfusion injury model [68, 69]. Moreover, statin could attenuate CI-AKI in rat model through modulation of oxidative stress and proinflammatory cytokines [70].

The clinical trials comparing efficacy of statins and placebo for prophylaxis of CI-AKI after contrast media administration are shown in Table 4. In 2004, Attallah et al. [71] retrospectively reviewed 1,002 medical records of the patients who started statin in hospital before the cardiac catheterization compared to those who were not administered statin. The baseline characteristics, SCr, GFR, amount of intravenous fluid, and contrast were similar in both groups. The postcatheterization SCr was significantly better in the statin group (P < 0.001). The percentages of patients with CI-AKI were 17.2 and 22.3% in the statin and no statin groups, respectively (P = 0.028). Khanal et al. [72] published their retrospective study of 29,409 patients undergoing percutaneous coronary intervention who received pre-procedure statin and those who did not. The incidences of CI-AKI were 4.37 versus 5.93 (P < 0.0001), and those of nephropathy requiring dialysis were 0.32 versus 0.49 (P = 0.03) in the patients who received statin and those who did not. In 2009, Xinwei et al. [73] performed the prospective randomized study to test whether the dosage of statins affects the efficacy of CI-AKI prophylaxis. The 284 patients with acute coronary syndrome undergoing coronary angiography were randomized 1 : 1 ratio into simvastatin 20 mg or 80 mg group. All patients were hydrated with intravenous 0.9% NaCl at a rate of 1mL/kgBW/h for 6 to 12 h before and 12 h after coronary angiography. The incidence of CI-AKI was significantly less in simvastatin 80 mg group compared to 20 mg group: 5.3 versus 15.7%, respectively. This study showed the importance of statins dosage in the efficacy to prevent CI-AKI.

The prospective, randomized, placebo-controlled trial for determining the efficacy of statins in CI-AKI prevention was performed by Jo et al. [74] in 2008. A total of 3,080 patients who underwent coronary catheterization were randomized to receive simvastatin 40 mg or placebo every 12 h for 2 days before the administration of contrast media. All patients were hydrated with intravenous 0.45% NaCl at a rate of 1mL/kgBW/h for 12 h before and after the procedure. The incidences of CI-AKI in both groups were similar: 2.5 and 3.4% in simvastatin and placebo groups, respectively. Several studies were performed using other statin, atorvastatin, to evaluate effect on CI-AKI prophylaxis. These studies have produced conflicting results [75-78]. Recently, there were 2 randomized controlled trials to determine the efficacy of rosuvastatin in CI-AKI prevention. First, Han et al. [79] randomized 2,998 patients with type 2 DM and CKD who were undergoing coronary or peripheral angiography to receive rosuvastatin 10 mg for 2 days before and 3 days after intervention or standard of care. The incidences of CI-AKI were significantly different: 2.3 and 3.9% in rosuvastatin and control groups, respectively (P = 0.01). Leoncini et al. [80] compared the incidence of CI-AKI in 504 patients with nonST elevated acute coronary syndrome undergoing coronary angiogram who receive rosuvastatin or no statin treatment on the admission. The incidence of CI-AKI was significantly lower in rosuvastatin group than in control group: 6.7 and 15.1%, respectively (P = 0.003).

2.9. Systematic Review and Meta-Analysis of the Efficacy of Statin for CI-AKI Prophylaxis. Zhang et al. [81] performed a meta-analysis of published randomized clinical trials to determine the efficacy of short-term administration of high-dose statin compared to placebo among patients undergoing catheterization in preventing CI-AKI. From 8 clinical trials including 1,423 patients, the study showed that high-dose statin treatment could decrease the incidence of CI-AKI (RR: 0.51, P = 0.001). However, the subgroup analysis showed that the incidence of CI-AKI was not different in the patients with preexisting renal impairment (RR: 0.9, P = 0.73). In contrast, the meta-analysis by Zhou et al. [82] including 5 trials with a total of 1,009 patients revealed that short-term, high-dose statin treatment lowered the incidence of AKI in patients with CKD stage 4 and stage 5 in 3 clinical trials, but not in patients with CKD stage 1 to stage 3 in 2 clinical trials. Zhang et al. [83] performed a systematic review and meta-analysis to determine the efficacy of long-term statin pretreatment to prevent the CI-AKI. Among 6 cohort studies, the chronic statin therapy pretreatment had a protective effect against CI-AKI. In contrast, from 6 randomized controlled trials with a total of 1,194 patients, the short-term, high-dose statin pretreatment had a nonsignificant protective effect against CI-AKI (RR 0.7, 95% CI: 0.48-1.02).

In summary, the current data regarding the efficacy of statins in CI-AKI prophylaxis are inconclusive. There is not enough evidence to support the use of statins in radiology patients. In the future, large well-designed studies are needed to address the efficacy of statins and their long-term clinical outcomes.

2.10. Ascorbic Acid (Vitamin C) for CI-AKI Prevention. Due to the antioxidant properties of ascorbic acid, the efficacy of ascorbic acid in the prevention of oxidative stress-associated diseases has been extensively studied. In animal model, vitamin C was able to attenuate the pathological process in the postischemic oxidative injuries and gentamicin and cisplatin induced nephrotoxicities [84-86]. In addition, ascorbic acid protected the kidney in CI-AKI rat model against oxidant stress by an antioxidant property [87].

The details of the clinical trials were summarized in Table 5. Spargias et al. [88] prospectively randomized 231 patients who were undergoing coronary angiography to receive oral ascorbic acid 3 g 2 h before and 2 g in the night and in the morning after the procedure or placebo. All patients were hydrated with 0.9% NaCl at a rate of 50-125 mL/h from randomization to at least 6h after the procedure. The incidences of CI-AKI were 9 and 20% in the ascorbic acid and placebo groups, respectively (P = 0.02).

However, the prospective, randomized clinical trials by Boscheri et al. [89], Jo et al. [90], and Zhou and Chen [91] showed the negative results of ascorbic acid in preventing the CI-AKI. Recently, Brueck et al. [92] prospectively randomized 520 patients who were undergoing CAG into 3 groups to receive (1) ascorbic acid 500 mg 24 h and 1 h before procedure, (2) NAC 600 mg 24 h and 1h before procedure, and (3) placebo. All patients received intravenous 0.9% NaCl at a rate of 1 mL/kgBW/h from 12 h before to 12 h after the procedure. The incidences of CI-AKI were not significantly different. Due to the conflicting results of ascorbic acid in preventing CI-AKI in at risk patients, the use of ascorbic acid for CI-AKI prophylaxis is deniable.

2.11. Tocopherol (Vitamin E) for CI-AKI Prevention. Tocopherol has been widely studied on its antioxidant property [84, 86], while using this agent for CI-AKI prophylaxis might be theoretically possible. A recent experimental study by Kongkham et al. on alpha tocopherol showed the renoprotective effect on the CI-AKI rat model by attenuating renal damage through antioxidant capacity.

The clinical trials on efficacy of using tocopherol for CI-AKI prophylaxis are summarized in Table 6. The first clinical trial in 2009 of Tasanarong et al. [93] randomized 103 patients who were undergoing coronary angiography to receive oral alpha tocopherol 525 IU once daily for 2 days before and on the day of procedure or placebo. All patients received intravenous 0.9% NaCl 1 mL/kgBW/h for 12 h before and 12 h after the angiography. Compared to placebo group, the incidence of CI-AKI was significantly lower in tocopherol group: 5.88 versus 23.08% (P = 0.02). In 2013, Tasanarong et al. [94] published a larger trial which enrolled 305 patients to ensure the positivity of the results. The patients who were undergoing elective coronary angiography were prospectively randomized into 3 groups to receive (1) alpha tocopherol 350 mg per day, (2) gamma tocopherol 300 mg per day, or (3) placebo. The prescribed regimen was initiated 5 days before and continued for 2 days after the angiography. All patients received intravenous 0.9% NaCl at a rate of 1 mL/kgBW/h for 12 h before and 12 h after the angiography The incidences of CI-AKIwere lower inboth groups of patients who receive tocopherol treatment: 4.9, 5.9, and 14.9%, respectively (P = 0.02).

In contrast, a smaller study by Kitzler et al. [95] showed a negative result. Thirty patients who were undergoing computed tomography with nonionic contrast media were randomized to receive oral 1200 mg of NAC, 540 mg of tocopherol emulsion, or placebo. All patients were hydrated with 0.45% NaCl at a rate of 1 mL/kgBW/h for 12 h before and 12 h after the procedure. No patient developed CI-AKI in this study.

Although the positive results of studies make vitamin E become an interesting option for CI-AKI prophylaxis, the sparse studies and inconsistent results cause a reluctance in using it. In the future, large well-designed studies are needed to prove the efficacy of these tocopherols in preventing CI-AKI.

2.12. Dopamine for CI-AKI Prevention. The vasoconstrictor effect of contrast media might play an important role in pathogenesis of CI-AKI. The benefit of dopamine might reduce the risk of CI-AKI by causing renal vasodilation and increasing renal blood flow. In animal model, administration of contrast media resulted in suppression of prostacyclin production, diminishing the renal blood flow, augmentation of medullary hypoxic injury, and histological changes at thick ascending limb of Henle's loop [96, 97]. The effect of low-dose dopamine infusion, called renal dose, is believed to cause renal artery vasodilatation. In human, intravenous infusion of dopamine was associated with an increase in renal blood flow in patients with heart failure [98]. These pharmacological properties might be beneficial in the prevention of CI-AKI.

The clinical trials of dopamine use for CI-AKI prophylaxis are summarized in Table 7. Kapoor et al. [99] randomized 40 patients who were undergoing coronary angiography to receive intravenous low-dose dopamine infusion or nothing. The rising in SCr and development of CI-AKI did not occur in any patient who received dopamine infusion. The study by Hans et al. [100] also showed a favorable outcome in the patients who received a dopamine infusion prior to peripheral angiography compared to placebo.

On the other hand, the studies by Abizaid et al. [101] and Stevens et al. [102] failed to demonstrate the benefit of dopamine infusion before the contrast media administration. Moreover, Abizaid et al. [101] showed that the patients who developed CI-AKI and received low-dose dopamine had a higher peak SCr, prolonged course of AKI, and prolonged length of hospital stays than patients who received saline alone. As a result of limited and inconsistent evidence of dopamine for CI-AKI prophylaxis and possibility of adverse outcome in patients who received dopamine treatment, the dopamine treatment for CI-AKI prophylaxis remains undesirable.

2.13. Fenoldopam for CI-AKI Prevention. Fenoldopam is a selective dopamine A1 receptor agonist and hypothetically increases renal blood flow in a similar manner to dopamine. This effect might be beneficial in the prevention of CI-AKI.

The clinical trials of fenoldopam use for CI-AKI prophylaxis are summarized in Table 8. In the first clinical trial [103], the patients were randomized to receive 0.45% NaCl alone or with fenoldopam or NAC. The incidences of CI-AKI were similar: 15.3,15.7, and 17.7%, respectively (P = 0.919). Stone et al. [104] conducted a larger prospective trial comparing patients who received fenoldopam in conjunction with 0.45% NaCl or 0.45% NaCl alone. There was no difference in CI-AKI incidence: 33.6 versus 30.1%, respectively (P = 0.61). Ng et al. [105] compared the patients who received intravascular volume expansion protocol with fenoldopam or NAC. There was no difference in the incidence of CIAKI: 20% versus 11.4%, respectively (P = 0.4). Moreover, the administration of fenoldopam resulted in decrease in blood pressure and increase in heart rate [104] which might be potentially harmful to the patients. In summary, all available evidence showed the negative results and undesirable side effect. Hence, the prophylactic use of fenoldopam for CI-AKI is disagreeable.

2.14. Theophylline for CI-AKI Prevention. In general, adenosine is an intrarenal vasoconstrictor and a mediator of the tubuloglomerular feedback mechanism. Theophylline, an adenosine antagonist, was logical to evaluate for risk reduction in CI-AKI. In animal model, the administration of contrast media resulted in an increased excretion of endogenous adenosine. Theophylline is an adenosine antagonist which might theoretically improve the renal hemodynamic in patients who receive contrast media. In experimental study, the decline of renal blood flow after contrast media administration was attenuated by theophylline [106].

The clinical trials of theophylline use for CI-AKI prophylaxis are summarized in Table 9. Two randomized studies by Huber et al. [107, 108] in 2002 and 2003 for evaluation the efficacy of theophylline versus placebo gave positive results. The incidence of CI-AKI was lower in the patients who receive theophylline. The more recent randomized studies also compared the efficacy of theophylline with saline, NAC with saline, and saline alone [109-112]. The incidence of CI-AKI was lower in theophylline group compared to saline group. Moreover, these studies showed comparable [109, 111] or even more preferable [110, 112] results of theophylline than NAC. However, Abizaid et al. [101] randomized 60 patients into 3 groups: (1) aminophylline with saline, (2) saline alone, and (3) dopamine with saline. The incidences of CI-AKI were similar: 35, 30, and 30%, respectively (P = 0.6). However, the requirement of RRT was slightly higher among the patients who received aminophylline with saline compared to others: 5 versus 0%.

Ix et al. [113] performed a meta-analysis including 7 trials with 480 patients and showed that mean change of SCr was lower in theophylline and aminophylline pretreatment group (P = 0.004). In 2012, Dai et al. [114] conducted a meta-analysis to determine the efficacy of theophylline in CI-AKI prevention. Sixteen trials with 1,412 patients were included. The study showed that theophylline significantly reduced the risk of CI-AKI (RR: 0.48, 95% CI: 0.26-0.89; P = 0.02). In contrast, Bagshaw and Ghali [115] published systematic review and meta-analysis and showed that pretreatment with theophylline had a trend toward reduction in CI-AKI incidence (RR: 0.40, 95% CI: 0.14-1.16; P = 0.09). Meta-analysis by Kelly et al. [58] with 531 patients from 6 trials showed a nonsignificant protective trend of theophylline for CI-AKI prevention (RR: 0.49, 95% CI: 0.23-1.06).

Due to inconsistent efficacy of theophylline across studies, the use of theophylline for CI-AKI prevention is not suggested.

2.15. Nebivolol for CI-AKI Prevention. Nebivolol is a [[beta].sub.1] receptor antagonist which has vasodilatory and antioxidant effect [116, 117]. After contrast media administration, the pretreated rats with nebivolol had less oxidative stress marker and histological abnormalities compared to those without nebivolol pretreatment [118].

Table 10 shows the details of clinical trials of nebivolol for CI-AKI prophylaxis. In 2011, Avci et al. [119] prospectively randomized 90 patients undergoing coronary angiogram to receive nebivolol 5 mg once daily with saline or metoprolol 50 mg once daily with saline. The incidence of CI-AKI was significantly lower in nebivolol group: 24 versus 33% (P = 0.039), respectively. Gunebakmaz et al. [120] randomized 120 patients who were undergoing coronary angiography into 3 groups: (1) nebivolol 5 mg once daily with saline, (2) saline alone, and (3) NAC with saline. The incidence of CI-AKI was numerically lower in nebivolol group: 20,27.5, and 22.5% (P = 0.72), respectively. In behalf of scanty studies in human, the use of nebivolol for CI-AKI prophylaxis is discouraged.

2.16. Atrial Natriuretic Peptide for CI-AKI Prevention. Atrial natriuretic peptide (ANP) is a potent endogenous natriuretic compound produced by cardiac myocytes in right atrium. In rat model, ANP infusion results in augmentation of glomerular filtration rate predominantly by a hemodynamic mechanism [121]. ANP treatment showed to ameliorate ischemic AKI in rat [122] and prevent CI-AKI in heart failure induced dogs [123].

Kurnik et al. [124] randomized 247 patients with CKD who were undergoing radiographic procedures which required contrast media administration to receive intravenous 0.45% saline for 12 h before and after the procedure or a combination of saline and one among three different rates of ANP infusion (0.01 [micro]g/kg/min, 0.05 [micro]g/kg/min, or 0.1 [micro]g/kg/min) for 30 min before and continuing for 30 min after the procedure. The incidences of CI-AKI were not different between 4 groups of patients. Morikawa et al. [125] randomized 254 patients with CKD who were undergoing coronary angiography to receive either ANP intravenous infusion at a rate of 0.042 [micro]g/kg/min or intravenous ringer solution alone at a rate of 1.3 mL/kg/h before and after the administration of contrast media. The incidences of CI-AKI were significantly lower in the ANP treatment group than in control group: 3.2 and 11.7%, respectively (P = 0.015). At 1 month, the incidences of an increase in SCr of [greater than or equal to] 25% or [greater than or equal to] 0.5mg/dL from baseline were also significantly lower in ANP-treated group than in the control group: 2.4 and 12.5%, respectively (P = 0.006). Due to sparse in number of evidences and inconsistent efficacies of ANP across the studies, the use of ANP for CI-AKI prevention is not indicative.

2.17. Prostaglandins for CI-AKI Prevention. Prostaglandins (PG) arise from enzymatic metabolism of arachidonic acid, which appeared in various parts of the kidney and had an effect on controlling renal blood flow and glomerular filtration rate [126]. In animal model, the vasodilatory effect of PG had an important role in maintaining blood flow to the poorly oxygenated region of the kidney [127], which directly counteracts the renal vasoconstrictive effect after the contrast media administration. Besides, an inhibition of PG synthesis in rats appeared to aggravate the renal injury from contrast media administration [16]. The infusion of PG had protective effects on renal function in either ischemia-reperfusion injury or contrast media administration model [128-130].

Gurkowski et al. [131] randomized 125 patients who were undergoing a radiologic contrast procedure to receive misoprostol, a synthetic [PGE.sub.1] analogue, 200 mg 4 times a day for 3 days before and 2 days after the procedure or a placebo. Misoprostol treatment showed to significantly attenuate the reduction of creatinine clearance. Spargias et al. [132] randomized 208 patients with CKD who were undergoing coronary angiography to receive iloprost, a synthetic analogue of PGI2, lng/kg/min for 30-90 minutes before and 4h after the procedure or placebo. The incidences of CI-AKI were lower in iloprost group than in control group: 8 and 22%, respectively (P = 0.005). Despite the positive results of the studies using PG analogue for CI-AKI prophylaxis, the sparse number of studies causes a reluctance in using it. Further studies are needed to prove the efficacy of PG analogue for CI-AKI prophylaxis.

3. Conclusion

CI-AKI is a common condition that is associated with increased morbidity and mortality, particularly in high risk patients. Volume expansion and treatment of dehydration are established interventions in the prevention of CI-AKI. Oral volume expansion has demonstrated some benefit, but there is not enough evidence to show that it is as effective as intravenous volume expansion. However, only intravascular volume expansion with isotonic saline solution or sodium bicarbonate is regarded as the only effective therapy and is recommended in the prevention of CI-AKI depending on the patient's volume status assessment. For isotonic saline administration, most studies suggest that 0.9% saline should be started at a rate [greater than or equal to] 1-1.5 mL/kg/h 3-12 h before and 6-12 h after contrast media exposure. Instead of sodium bicarbonate administration, most studies suggest that sodium bicarbonate should be started at a rate of 3 mL/kg/h 1 h before and 1 mL/kg/h 6 h after contrast media exposure.

There are varieties of pharmacological interventions for CI-AKI prophylaxis that has been developed in many experimental studies and clinical trials. Based on the evidence tables and even taking the most recent study, there are no currently approved pharmacologic agents for the prevention of CI-AKI. Overall evidence of NAC is not consistent or overwhelming, but oral NAC has a low risk of adverse events and usually a low cost. We suggest using oral NAC combined with standard intravenous volume expansion in patients with increased risk of CI-AKI. Recent clinical trials for early high-dose or short-term statin demonstrated the benefit for preventing CI-AKI. In the future, large, well-designed, and adequately powered randomized clinical trials are urgently needed to study this important issue. Other agents, theophylline, nebivolol, prostaglandin, ANP, dopamine, and fenoldopam, showed some benefit reports, but the majority of evidence showed conflicting results and some therapies were even harmful. In addition, the novel pharmacological strategies such as ascorbic acid and tocopherol are required to prove their benefit in preventing CI-AKI in the future.

Future approaches include large plan excellent clinical trials of oral or intravenous antioxidants, vasodilators, or novel pharmacologic agents combined with intravenous volume expansion to decrease the incidence of CI-AKI. Newer criteria for early diagnosis of CI-AKI by rising SCr, changing urine output, and/or novel biomarker need to be developed and used to be the standard criteria for general practices.

http://dx.doi.org/10.1155/2014/236930

Conflict of Interests

The authors declare that there is no conflict of interests regarding the publication of this paper.

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Pattharawin Pattharanitima and Adis Tasanarong

Nephrology Unit, Department of Medicine, Faculty of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathumtani 12121, Thailand

Correspondence should be addressed to Adis Tasanarong; adis_tasanarong@hotmail.com

Received 19 October 2013; Revised 3 January 2014; Accepted 7 January 2014; Published 26 February 2014

Academic Editor: Michele Andreucci
TABLE 1: Meta-analysis comparing the efficacy of sodium
bicarbonate and sodium chloride for contrast-induced
AKI prophylaxis.

                  References

Authors                    Year   Number of   Number of
                                  patients     trials

Hogan et al. [38]          2008     1,307         7
Kanbay et al. [39]         2009     2,448        17
Navaneethan et al. [40]    2009     1,652        12
Zoungas et al. [41]        2009
(i) Published studies               1,846         9
(ii) Unpublished studies            1,717        14
Kunadian et al. [42]       2011     1,734         7
Janget al. [37]            2012     3,609        19

References                            95% CI

Authors                     RR     Low     High    P value

Hogan et al. [38]          0.37    0.18    0.714    0.005
Kanbay et al. [39]         0.54    0.36    0.83      ND
Navaneethan et al. [40]    0.46    0.26    0.82     0.008
Zoungas et al. [41]
(i) Published studies      0.43    0.25    0.75     0.02
(ii) Unpublished studies   0.78    0.52    1.17     0.05
Kunadian et al. [42]       0.33    0.16    0.69     0.003
Janget al. [37]            0.56    0.36    0.86     0.008

TABLE 2: Prospective, randomized clinical trials comparing
N-acetylcysteine with placebo for prophylaxis of contrast
-induced AKI after angiography

Authors                Year      Inclusion          Type of
                                  criteria       procedure and
                                                 contrast media

Tepel et al. [47]      2000   Cr >1.2mg/dL or    CECT Iopromide
                              GFR <50 mL/min/
                               1.73 [m.sup.2]

Shyu et al. [48]       2002   Cr 2-6 mg/dL or    CAG Iopamidol
                               GFR 8- 40 mL/
                                  min/1.73
                                 [m.sup.2]

Kay et al. [49]        2003    Cr >1.2 mg/dL     CAG Iopamidol
                                 or GFR <60
                                mL/min/1.73
                                 [m.sup.2]

Baskurt et al.         2009      GFR 30- 60       CAG loversol
[110]                           mL/min/1.73
                                 [m.sup.2]

Boccalandro et al.     2003   Cr >1.2 mg/dL or   CAG Iodixanol
[133]                         GFR <50 mL/min/
                               1.73 [m.sup.2]

Webb et al. [50]       2004   GFR <50 mL/min/     CAG loversol
                               1.73 [m.sup.2]

Gomes et al. [134]     2005    Cr >1.2 mg/dL     CAG Ioxaglate

Ozcan et al. [135]     2007    Cr 1.2-4 mg/dL    CAG Ioxaglate

ACT                    2011   At least 1 risk      CAG/PAG ND
investigators [3]                factor for
                                CI-AKI (Age
                                 >70 years,
                               Cr >1.5 mg/dL,
                               DM, CHF, LVEF
                                   <0.45,
                                hypotension)

                                                Study protocol
Authors                Number of patients
                       Intervention versus      Intervention
                             control

Tepel et al. [47]         41 versus 42       NAC 600 mg po bid

Shyu et al. [48]          60 versus 61       NAC 400 mg po bid

Kay et al. [49]           102 versus 98      NAC 600 mg po bid

Baskurt et al.              73 versus        NAC 600 mg po bid
[110]                     72 versus 72

Boccalandro et al.        75 versus 106      NAC 600 mg po bid
[133]

Webb et al. [50]         242 versus 245        Single dose of
                                             NAC 500 mg in D5W
                                             50 mL IV lh before

Gomes et al. [134]        77 versus 79       NAC 600 mg po bid
                                             2 doses before and
                                                   after

Ozcan et al. [135]          88 versus        NAC 600 mg po bid
                          88 versus 88       with NSS 1 mL/kg/h
                                             6 hours before and
                                                   after

ACT                    1,172 versus 1,136    NAC 600 mg po bid
investigators [3]

                          Study protocol
Authors                                      Intravascular volume
                             Control          expansion protocol

Tepel et al. [47]             None              N/2 1 mL/kg/h
                                               12 hours before
                                                  and after

Shyu et al. [48]             Placebo              0.45% NaCl
                                              1 mL/kg/h 12 hours
                                               before and after

Kay et al. [49]              Placebo            NSS 1 mL/kg/h
                                             12 hours before and
                                              6 hours after with
                                              liberal oral fluid

Baskurt et al.              (1) None            NSS 1 mL/kg/h
[110]                  (2) NAC 600 mg and      12 hours before
                       theophylline 200 mg        and after
                             po bid

Boccalandro et al.            None            0.45% NaCl 75 mL/h
[133]                                        12 hours before and
                                                    after

Webb et al. [50]            D5W 50 mL         NSS 200 mL before
                                                and 1.5 mL/kg
                                                6 hours after

Gomes et al. [134]           Placebo            NSS 1 mL/kg/h
                                               12 hours before
                                                  and after

Ozcan et al. [135]        1 mL/kg/h for               --
                       6 hours before and
                            after of
                          (1) Isotonic
                            NaHCOs IV
                           (2) NSS IV

ACT                          Placebo           NSS 1 mL/kg/h x
investigators [3]                             6-12 hours before
                                                  and after

                                              Incidence of CI-AKI

Authors                 CI-AKI definition     Intervention versus
                                                  control (%)

Tepel et al. [47]         [up arrow] Cr           2 versus 21
                         [greater than or
                       equal to] 25%/2 d or
                          [up arrow] Cr
                         [greater than or
                        equal to] 0.5/2 d

Shyu et al. [48]          [up arrow] Cr         3.3 versus 24.6
                         [greater than or
                        equal to] 0.5/2 d

Kay et al. [49]           [up arrow] Cr           4 versus 12
                         [greater than or
                        equal to] 25%/2 d

Baskurt et al.            [up arrow] Cr           9.6 versus
[110]                    [greater than or        6.9 versus 0
                        equal to] 0.5/2 d

Boccalandro et al.        [up arrow] Cr          13 versus 12
[133]                    [greater than or
                        equal to] 0.5/2 d

Webb et al. [50]         [down arrow] GFR      23.3 versus 20.7
                         [greater than or
                       equal to] 5 mL/min/
                          1.73 [m.sup.2]

Gomes et al. [134]        [up arrow] Cr        10.4 versus 10.1
                         [greater than or
                        equal to] 0.5/2 d

Ozcan et al. [135]        [up arrow] Cr           12.5 versus
                         [greater than or       4.5 versus 13.6
                        equal to] 25%/2 d
                         or [up arrow] Cr
                         [greater than or
                        equal to] 0.5/2 d

ACT                        1Cr 25%/2-4d        12.7 versus 12.7
investigators [3]

                       Incidence
                       of CI-AKI

                                     RRT requirement
Authors                 P value    Intervention versus
                                       control (%)

Tepel et al. [47]        0.01          0 versus 0

Shyu et al. [48]        <0.001             ND

Kay et al. [49]          0.03              ND

Baskurt et al.           0.033         0 versus 0
[110]

Boccalandro et al.       0.842             ND
[133]

Webb et al. [50]         0.51          20 versus 0

Gomes et al. [134]       1.00         2.6 versus 0

Ozcan et al. [135]       0.706          0 versus
                         0.081       1.1 versus 1.1

ACT                      0.97        2.2 versus 2.3
investigators [3]

bid: twice daily; CAG: coronary angiography;
CECT: contrast enhanced computed tomography;
CI-AKI: contrast-induced acute kidney injury;
CHF: congestive heart failure; Cr: creatinine; d:
day; DM: diabetes mellitus; D5W: 5% dextrose solution;
GFR: glomerular filtration rate; h: hour;
IV: intravenous; kg: kilogram body weight;
LVEF: left ventricular ejection fraction;
mg: milligram; mL: milliliter; NAC: N-acetylcysteine;
ND: no data; NSS: normal saline solution; N/2: 0.45%
NaCl; PAG: peripheral angiography; po: per oral route;
RRT: renal replacement therapy.

TABLE 3: Systematic review and meta-analysis comparing
the efficacy of N-acetylcysteine and placebo
for contrast-induced AKI prophylaxis.

                References

Authors                   Year   Number of   Number of
                                 patients     trials

Birck et al. [51]         2003      805          7
Isenbarger et al. [52]    2003      805          7
Alonso et al. [53]        2004      885          8
Bagshaw and Ghali [54]    2004     1,261        14
Pannu et al. [55]         2004     1,776        15
Duong et al. [56]         2005     1,584        14
Liu et al. [57]           2005     1,028         9
Kelly et al. [58]         2008     6,379        41
Kwok et al. [59]          2013    15,976         7
Kshirsagar et al. [60]    2004     1,538        16
Mirsa et al. [61]         2004      ND          27
Nallamothu et al. [62]    2004     2, 195        21
Zagler et al. [63]        2006     1,892        13
Gonzales et al. [64]      2007     2,476        22
ACT Investigators [3]     2011     1,000         5
Sun et al. [65]           2013     1,916        10

References                            95%CI

Authors                    RR      Low    High    P value

Birck et al. [51]         0.435   0.215   0.879    0.02
Isenbarger et al. [52]    0.37    0.16    0.84      ND
Alonso et al. [53]        0.41    0.22    0.79     0.007
Bagshaw and Ghali [54]    0.54    0.32    0.91     0.02
Pannu et al. [55]         0.65    0.43     1.0     0.049
Duong et al. [56]         0.57    0.37    0.84     0.01
Liu et al. [57]           0.43    0.24    0.75      ND
Kelly et al. [58]         0.62    0.44    0.88      ND
Kwok et al. [59]          0.65    0.48    0.88      ND
Kshirsagar et al. [60]     ND      ND      ND       ND
Mirsa et al. [61]          ND      ND      ND       NS
Nallamothu et al. [62]    0.73    0.52     1.0     0.08
Zagler et al. [63]        0.68    0.46    1.02     0.06
Gonzales et al. [64]      0.87    0.68    1.12     0.28
ACT Investigators [3]     1.05    0.73    1.53      ND
Sun et al. [65]           0.68    0.46    1.02     0.06

95% CI: 95% confidence interval; ND: no available data;
NS: nonsignificant; RR: relative risk.

TABLE 4: Prospective, randomized clinical trials comparing
efficacy of statins and placebo for contrast-induced
AKI after angiography prophylaxis.

Authors           Year   Type of procedure    Number of patients
                         and contrast media   Intervention versus
                                              control

Xinwei            2009     CAG Iodixanol        115 versus 113
et al. [73]

Patti et al.      2011     CAG Iobitridol       120 versus 121
[77]

Quintavalle       2012     CAG Iodixanol        202 versus 208
et al. [78]

Jo etal. [74]     2008     CAG Iodixanol        124 versus 123

Ozhan et al.      2010         CAG ND              Total 130
[75]

Toso et al.       2010     CAG Iodixanol        152 versus 152
[76]

Han etal. [79]    2013   CAG/PAG Iodixanol     1498 versus 1500

Leoncini          2013     CAG Iodixanol        252 versus 252
et al. [80]

Authors                       Study protocol

                     Intervention           Control

Xinwei                Simvastatin       Simvastatin 80
et al. [73]             20 mg/d         mg/d before and
                                          20 mg after

Patti et al.      Atorvastatin 80 mg        Placebo
[77]              12 hours and 40 mg
                    2 hours before

Quintavalle       Atorvastatin 80 mg         None
et al. [78]          1 days before

Jo etal. [74]      Simvastatin 40 mg        Placebo
                  po ql2h for 2 days

Ozhan et al.         Atorvastatin            None
[75]

Toso et al.          Atorvastatin           Placebo
[76]                80 mg/d 2 days
                   before and after

Han etal. [79]       Rosuvastatin            None
                    10 mg/d 2 days
                   before and 3 days
                         after

Leoncini             Rosuvastatin            None
et al. [80]       40 mg on admission
                     then 20 mg/d

Authors           Intravascular         CI-AKI definition
                  volume expansion
                  and NAC protocol

Xinwei             NSS lmL/kg/h 6-12      [up arrow] Cr
et al. [73]        hours before and      [greater than or
                    12 hours after       equal to] 25%/2
                                        days or [up arrow]
                                         Cr [greater than
                                        or equal to] 0.5/2
                                               days

Patti et al.         NSS 1 mL/kg/h        [up arrow] Cr
[77]               [greater than or      [greater than or
                  equal to] 12 hours    equal to] 25%/l-2
                  before and 24 hours   days or [up arrow]
                         after           Cr [greater than
                                        or equal to] 0.5/
                                             l-2 days

Quintavalle            Isotonic          [up arrow] CysC
et al. [78]          NaHC[0.sub.3]       [greater than or
                   3 mL/kg/h 1 hour      equal to] 10%/1
                     and 1 mL/kg/h      day [up arrow] Cr
                      6 hours NAC        [greater than or
                    1200 mg po bid       equal to] 25%/2
                                        days or [up arrow]
                                         Cr [greater than
                                        or equal to] 0.5/2
                                               days

Jo etal. [74]        N/2 1 mL/kg/h        [up arrow] Cr
                    12 hours before      [greater than or
                       and after         equal to] 25%/2
                                        days or [up arrow]
                                         Cr [greater than
                                           or equal to]
                                            0.5/2 days

Ozhan et al.              NAC                   ND
[75]

Toso et al.          NSS 1 mL/kg/h        [up arrow] Cr
[76]                12 hours before      [greater than or
                     and after NAC       equal to] 0.5/5
                    1200 mg po bid      days or [up arrow]
                                        Cr [greater than
                                        or equal to] 25%/5
                                               days

Han etal. [79]       NSS 1 mL/kg/h        [up arrow] Cr
                    12 hours before      [greater than or
                  and 24 hours after     equal to] 25%/3
                                        days or [up arrow]
                                         Cr [greater than
                                        or equal to] 0.5/3
                                               days

Leoncini             NSS 1 mL/kg/h        [up arrow] Cr
et al. [80]         12 hours before      [greater than or
                     and after NAC       equal to] 25%/3
                    1200 mg po bid      days or [up arrow]
                                         Cr [greater than
                                           or equal to]
                                            0.5/3 days

                                        Incidence of CI-AKI
Authors           Mean GFR
                  Intervention versus   Intervention
                  control               versus control
                  (mL/min/1.73          (%)
                  [m.sup.2])

Xinwei             86.5 versus 93.6       15.7 versus 5.3
et al. [73]

Patti et al.       79.8 versus 77.0        5 versus 13.2
[77]

Quintavalle          42 versus 43         4.5 versus 17.8
et al. [78]

Jo etal. [74]      53.46 versus 55.4      2.5 versus 3.4

Ozhan et al.              ND                2 patients
[75]                                    versus 7 patients *

Toso et al.          46 versus 46         9.7 versus 11.2
[76]

Han etal. [79]    74.16 versus 74.43      2.3 versus 3.9

Leoncini           82.5 versus 82.6       6.7 versus 15.1
et al. [80]

Authors           Incidence
                  of CI-AKI   RRT requirement
                              Intervention versus
                   P value    control (%)

Xinwei              <0.05             ND
et al. [73]

Patti et al.        0.046        0 versus 0.8
[77]

Quintavalle         0.005             ND
et al. [78]

Jo etal. [74]        1.0         0 versus 0.8

Ozhan et al.         NS               ND
[75]

Toso et al.         NS NS        0 versus 0.7
[76]

Han etal. [79]      0.01         0 versus 0.1

Leoncini            0.003        0 versus 0.1
et al. [80]

* The incidences of CI-AKI data in each group are not available.
Data is shown as the number of patients who develop CI-AKI.
bid: twice daily; CAG: coronary angiography; CI-AKI: contrast
-induced acute kidney injury; Cr: creatinine; CysC: cystatin C;
d: day; h: hour; IV: intravenous; kg: kilogram body weight;
mg: milligram; mL: milliliter; NAC: N-acetylcysteine;
ND: no data; NSS: normal saline solution; N/2: 0.45%
NaCl; po: per oral route; PAG: peripheral angiography;
q12h: every 12 hours; RRT: renal replacement therapy.

TABLE 5: Prospective, randomized clinical trials comparing
efficacy of vitamin C with placebo and other agents
for contrast-induced AKI after angiography prophylaxis.

Authors           Year   Type of procedure   Number of patients
                         and contrast        Intervention
                         media               versus control

Spargias          2004      CAG LONICM         118 versus 113
et al. [88]                  or IONICM

Boscheri          2007        CAG ND            74 versus 69
et al. [89]

Jo etal. [90]     2009     CAG Iodixanol       106 versus 106

Zhou and chen     2012    CAG Unspecified       74 versus 82
[91]

Brueck et al.     2013     CAG Iopromide         104 versus
[92]                                           208 versus 208

Authors                           Study protocol

                       Intervention              Control

Spargias            Ascorbic acid 3 g            Placebo
et al. [88]       po 2 hours before and
                   2 g in the night and
                   in the morning after

Boscheri            Ascorbic acid 1 g            Placebo
et al. [89]

Jo etal. [90]     Ascorbic acid po ql2h     NAC 1200 mg po bid
                   3 and 2 g before and     4 doses, begin 1st
                     2 and 2 g after       dose in the evening
                                                  before

Zhou and chen       Ascorbic acid 3 g            Placebo
[91]              IV before and 0.5 g po
                  ql2h for 2 days after

Brueck et al.      Ascorbic acid 500 mg    (1) NAC 600 mg iv at
[92]                IV at 24 hours and     24 hours and 1 hour
                      1 hour before         before (2) Placebo

Authors           Intravascular           CI-AKI definition

                  volume expansion
                  and NAC protocol

Spargias          NSS 50-125 mL/h from        [up arrow] Cr
et al. [88]         randomization to      [greater than or equal
                      6 hours after         to] 25%/2 days or
                                              [up arrow] Cr
                                          [greater than or equal
                                              to] 0.5/2 days

Boscheri          NSS before and after              ND
et al. [89]

Jo etal. [90]     N/2 lmL/kg/h 12 hours       [up arrow] Cr
                    before and after         [greater than or
                                           equal to] 25%/2 days
                                             or [up arrow] Cr
                                             [greater than or
                                           equal to] 0.5/2 days

Zhou and chen     NSS 1 mL/kg/h 4 hours       [up arrow] Cr
[91]               before and 12 hours       [greater than or
                          after            equal to] 25%/2 days
                                             or [up arrow] Cr
                                          [greater than or equal
                                              to] 0.5/2 days

Brueck et al.         NSS 1 mL/kg/h           [up arrow] Cr
[92]               12 hours before and    [greater than or equal
                     12 hours after           to] 0.5/3 days

                                         Incidence of CI-AKI
Authors           Mean GFR
                  Intervention versus       Intervention
                  control                  versus control
                  (mL/min/1.73 nr)               (%)

Spargias            61.1 versus 68.1         9 versus 20
et al. [88]

Boscheri                   ND              6.8 versus 4.3
et al. [89]

Jo etal. [90]       53.7 versus 53.7       4.4 versus 1.2

Zhou and chen       52.5 versus 53.2       6.3 versus 5.4
[91]

Brueck et al.         43.0 versus         24.5 versus 27.6
[92]                40.2 versus 42.0         versus 32.1

                  Incidence
Authors           of CI-AKI   RRT requirement
                              Intervention versus
                   P value    control (%)

Spargias            0.02              ND
et al. [88]

Boscheri             NS               ND
et al. [89]

Jo etal. [90]       0.370         2 versus 1

Zhou and chen       0.69              ND
[91]

Brueck et al.      0.11 *         0 versus 0
[92]               0.20 **         versus 0

P value of * ascorbic acid and NAC compared to placebo group.
bid: twice daily; CAG: coronary angiography; CI-AKI: contrast
-induced acute kidney injury; Cr: creatinine; g: gram; h: hour;
IONICM: isoosmolarity nonionic contrast media; IV: intravenous;
kg: kilogram body weight; LONICM: low osmolarity nonionic contrast
media; kg: kilogram body weight; mg: milligram; mL: milliliter;
NAC: N-acetylcysteine; ND: no data; NSS: normal saline solution;
N/2: 0.45% NaCl; po: per oral route; q12h: every 12 hours;
RRT: renal replacement therapy.

TABLE 6: Prospective, randomized clinical trials comparing
efficacy of vitamin E with placebo and other agents for
contrast-induced AKI after angiography prophylaxis.

Authors           Year   Type of procedure    Number of patients
                         and contrast media   Intervention versus
                                              control

Tasanarong        2009     CAG Iopromide         51 versus 52
et al. [93]

                                                  102 versus
Tasanarong        2013                            102 versus
et al. [93]                                           101

Kitzler et al.    2012           CT                10 versus
[95]                         Iopromide           10 versus 10

Authors                        Study protocol

                     Intervention             Control

Tasanarong         Alpha tocopherol           Placebo
et al. [93]         525IU po OD for
                     2 days before

                   Po 5 days before           Placebo
Tasanarong         and 2 days after
et al. [93]         of (1) [alpha]-
                  tocopherol 350 mg/d
                     (2) [gamma]-
                  tocopherol 300 mg/d

Kitzler et al.    Vitamin E emulsion    (1) NAC 1200 mg po
[95]                540 mg IV every        every 6 hours
                   6 hours 12 hours     12 hours before and
                   before and after     after plus placebo
                                            (2) Placebo

Authors           Intravascular      CI-AKI definition
                  volume expansion
                  and NAC protocol

Tasanarong          NSS lmL/kg/h     [up arrow] Cr
et al. [93]       12 hours before    [greater than or
                     and after       equal to] 25%/
                                     2 days or
                                     [up arrow] Cr
                                     [greater than or
                                     equal to] 0.5/2
                                     days

                    NSS lmL/kg/h     [up arrow] Cr
Tasanarong        12 hours before    [greater than or
et al. [93]          and after       equal to] 25%/2
                                     days or [up arrow]
                                     Cr [greater than or
                                     equal to] 0.5/2 days

Kitzler et al.     N/2 1 mL/kg/h     [up arrow] Cr
[95]              12 hours before    [greater than or
                     and after       equal to] 25%/
                                     2 days

                                          Incidence
                                          of CI-AKI

Authors           Mean GFR
                  Intervention versus      Intervention
                  control                 versus control
                  (mL/min/1.73                  (%)
                  [m.sup.2])

Tasanarong        41 versus 42           5.88 versus 23.08
et al. [93]

                  45 versus                 4.9 versus
Tasanarong        46 versus                 5.9 versus
et al. [93]       43                           14.9

Kitzler et al.    64 versus                  0 versus
[95]              56 versus 63              0 versus 0

                  Incidence
Authors           of CI-AKI   RRT requirement
                              Intervention versus
                   P value    control (%)

Tasanarong          0.02          0 versus 0
et al. [93]

                                   0 versus
Tasanarong          0.02           0 versus
et al. [93]                            0

Kitzler et al.       NS               ND
[95]

CAG: coronary angiography; CI-AKI: contrast-induced
acute kidney injury; Cr: creatinine; CysC: cystatin C;
CT: computed tomography; d: day; h: hour; IV: intravenous;
kg: kilogram body weight; mg: milligram; mL: milliliter;
NAC: N-acetylcysteine; ND: no data; N/2: 0.45% NaCl;
OD: once daily; po: per oral route; q12h: every 12 hours;
RRT: renal replacement therapy.

TABLE 7: Prospective, randomized clinical trials comparing
efficacy of dopamine with placebo and other agents for
contrast-induced AKI after angiography prophylaxis.

                        Type of procedure    Number of patients
                        and contrast media   Intervention versus
Authors          Year                        control

Hans et al.      1998          PAG                28 versus
[100]                        Iohexol                 27

Kapoor et al.    1996          CAG                20 versus
[99]                       Urograffi n               20

Abizaid et al.   1999          CAG                20 versus
[101]                        Hexabrix           20 versus 20

Stevens et al.   1999          CAG                22 versus
[102]                           ND              21 versus 55

                          Study protocol

Authors          Intervention          Control

Hans et al.           Dopamine                NSS
[100]            2.5mcg/kg/h 1 hour
                 before and 11 hours
                        after

Kapoor et al.         Dopamine               None
[99]                5mcg/kg/h 30
                 minutes before and
                   6-8 hours after

Abizaid et al.        Dopamine             (1) None
[101]                2.5mcg/kg/h       (2) Aminophylline
                                        IV 4mg/kg then
                                          0.4mg/kg/h

Stevens et al.        Dopamine           (1) Dopamine
[102]                3mcg/kg/h,          3mcg/kg/h and
                  Furosemide 1mg/kg    Furosemide 1mg/kg
                   IV before, and          IV before
                 Mannitol 12.5 g in        (2) None
                  D5W 250mL IV in 2
                        hours

                 Intravascular
                 volume expansion
Authors          and NAC protocol      CI-AKI definition

Hans et al.             None              [up arrow] Cr
[100]                                    [greater than or
                                       equal to] 0.5/2 days

Kapoor et al.           None              [up arrow] Cr
[99]                                     [greater than or
                                       equal to] 25%/1 day
                                          [up arrow] Cr
                                         [greater than or
                                         equal to] 25%/3
                                               days

Abizaid et al.      N/2 1 mL/kg/h         [up arrow] Cr
[101]            12 hours before and     [greater than or
                        after          equal to] 25%/2 days

Stevens et al.     N/2 150 mL/h 6         [up arrow] Cr
[102]             hours after then       [greater than or
                   adjust to match        equal to] 25%/
                    urine output            0.5-2 days

                 Mean GFR              Incidence of CI-AKI
                 Intervention versus
                 control               Intervention
                 (mL/min/1.73          versus control
Authors          [m.sup.2])            (%)

Hans et al.         42.18 versus           7.1 versus
[100]                   48.8                  28.6

Kapoor et al.         * Cr 1.50             0 versus
[99]                 versus 1.52               50

Abizaid et al.     * Cr 1.9 versus          50 versus
[101]              2.3 versus 1.9         30 versus 35

Stevens et al.      33.73 versus           31.8 versus
[102]            31.44 versus 30.48     33.3 versus 30.9

                 Incidence
                 of CI-AKI   RRT requirement
                             Intervention versus
Authors                      control (%)
                 P value

Hans et al.        0.026             ND
[100]

Kapoor et al.       ND            0 versus
[99]                                  0

Abizaid et al.      0.6           0 versus
[101]                            0 versus 5

Stevens et al.     0.98          4.5 versus
[102]                          4.8 versus 9.1

* Mean GFR data is not available. Data is shown as mean
serum creatinine in mg/dL. CAG: coronary angiography; CI-AKI:
contrast-induced acute kidney injury; Cr: creatinine;
g: gram; D5W: 5% dextrose solution; h: hour; IV: intravenous;
kg: kilo gram body weight; mcg: microgram; mg: milligram; mL:
milliliter, NAC: N-acetylcysteine; ND: no data; N/2: 0.45%
NaCl; PAG: peripheral angiography; po: per oral route; q12h:
every 12 hours; RRT: renal replacement therapy.

TABLE 8: Clinical trials comparing fenoldopam with placebo
and other agents for prophylaxis of contrast-induced AKI
after angiography.

Authors        Year   Type of procedure    Number of patients
                      and contrast media   Intervention versus
                                           control

Allaqab and    2002       CAG LONICM          38 versus 40
et al. [103]                                    versus 45

Stone et al.   2003         CAG ND           157 versus 158
[104]

Ng et al.      2006       CAG LONICM          47 versus 48
[105]                     and IONICM

Authors                     Study protocol

                  Intervention            Control

Allaqab and      Fenoldopam 0.1          (1) None
et al. [103]   meg/kg/h IV 4 hours    (2) NAC 600 mg
                before and after          po bid

Stone et al.   Fenoldopam 0.05-0.1        Placebo
[104]          meg/kg/h IV 1 hour
               before and 12 hours
                      after

Ng et al.        Fenoldopam 0.1      NAC 600 mg po bid
[105]            meg/kg/h IV 1-2
                hours before and
                  6 hours after

Authors        Intravascular
               volume expansion
               and NAC protocol      CI-AKI definition

Allaqab and       N/2 1 mL/kg/h         [up arrow] Cr
et al. [103]     12 hours before       [greater than or
                    and after        equal to] 0.5/2 days

Stone et al.     N/2 1.5 mL/kg/h        [up arrow] Cr
[104]           2-12 hours before      [greater than or
               (1 mL/kg/h if CHF)     equal to] 25%/l-4
                                             days

Ng et al.          NSS or D5W           [up arrow] Cr
[105]          1 mL/kg/h 1-2 hours     [greater than or
                   before and         equal to] 25%/l-3
                6-12 hours after         days or TCr
                                       [greater than or
                                      equal to] 0.5/1-3
                                             days

                                         Incidence of CI-AKI
               Mean GFR
Authors        Intervention versus       Intervention
               control                   versus control
               (mL/min/1.73 [m.sup.2])   (%)

Allaqab and       35.5 versus 34.1        15.7 versus 15.3
et al. [103]         versus 36.9             versus 17.7

Stone et al.      29.0 versus 29.1        33.6 versus 30.1
[104]

Ng et al.       * Cr 1.53 versus 1.46     20.0 versus 11.4
[105]

               Incidence
Authors        of CI-AKI   RRT requirement
                           Intervention versus
                P value    control (%)

Allaqab and      0.919        ** Total 1.62
et al. [103]

Stone et al.     0.61        2.6 versus 1.9
[104]

Ng et al.        0.40              ND
[105]

* Mean GFR data is not available. Data is shown
as mean serum creatinine in mg/dL.

** Percentage of RRT requirement data in each group
is not available. Data is shown as percentage of RRT
requirement in all patients.

bid: twice daily; CAG: coronary angiography;
CHF: congestive heart failure; CI-AKI: contrast-induced
acute kidney injury; Cr: creatinine; g: gram;
D5W: 5% dextrose solution; h: hour; IONICM: isoosmolarity
nonionic contrast media; IV: intravenous; kg: kilogram body
weight; LONICM: low osmolarity nonionic contrast media;
meg: microgram; mg: milligram; mL: milliliter; NAC:
N-acetylcysteine; ND: no data; NSS: normal saline solution;
N/2: 0.45% NaCl; po: per oral route; ql2h: every 12 hours;
RRT: renal replacement therapy.

TABLE 9: Clinical trials comparing theophylline with placebo
and other agents for prophylaxis of contrast-induced
AKI after angiography.

Authors          Year    Type of procedure     Number of patients
                         and contrast media    Intervention versus
                                               control

Huber et al.     2002          CAG/PAG              50 versus
[107]                         Iomeprol                 50

Huber et al.     2003            CAG                50 versus
[108]                          Imeron                  50

Dussol et al.    2006    Various procedures         80 versus
[33]                         Ioxaglate,             76 versus
                           iobitriodol and        77 versus 79
                              iopromide

Huber et al.     2006    Various procedures         51 versus
[109]                          Imeron             50 versus 49

Baskurt et al.   2009            CAG                72 versus
[110]                         Ioversol            72 versus 73

Kinbara et al.   2010            CAG              15 versus 15
[111]                         Iopamidol

Bilasy et al.    2012            CAG                30 versus
[112]                         Iopamidol                30

Abizaid et al.   1999            CAG                20 versus
[101]                         Hexabrix            20 versus 20

                                 Study protocol

Authors               Intervention               Control

Huber et al.      Theophylline 200 mg            Placebo
[107]             IV 30 minutes before

Huber et al.      Theophylline 200 mg            Placebo
[108]             IV 30 minutes before

Dussol et al.         Theophylline         (1) NaCl 0.1 g/kg po
[33]                 5mg/kg 1 hour                2 days
                         before            (2) NSS 15 ml/kg IV
                                                 6 hours
                                           (3) (2) NSS 15mL/kg
                                              IV 6 hours and
                                            Furosemide 3mg/kg
                                                    IV

Huber et al.      Theophylline 200 mg        (1) NAC 600mg IV
[109]             IV 30 minutes before             bid
                                             (2) Combination

Baskurt et al.     Theophylline200 mg            (1) None
[110]                      +                 2) NAC 600mg po
                    NAC 600mg po bid               bid

Kinbara et al.    Theophylline 250 mg            (1) None
[111]             IV 30 minutes before       2) NAC 704mg po
                                                   bid

Bilasy et al.     Theophylline 200 mg          Placebo and
[112]              in NSS 100mL IV 30        NAC 600mg po bid
                   minutes before and
                    NAC 600mg po bid

Abizaid et al.      Aminophylline IV             (1) None
[101]                 4mg/kg then              (2) Dopamine
                   0.4mg/kg/h 2 hours      2.5mcg/kg/h 2 hours
                         before                   before

Authors          Intravascular            CI-AKI definition
                 volume expansion
                 and NAC protocol

Huber et al.               ND                 [up arrow] Cr
[107]                                        [greater than or
                                           equal to] 0.5/2 days

Huber et al.               ND                 [up arrow] Cr
[108]                                        [greater than or
                                           equal to] 0.5/2 days

Dussol et al.              ND                 [up arrow] Cr
[33]                                         [greater than or
                                           equal to] 0.5/2 days

Huber et al.          According to            [up arrow] Cr
[109]              underlying disease        [greater than or
                                           equal to] 0.5/2 days

Baskurt et al.      NSS 1 mL/kg/h 12          [up arrow] Cr
[110]               hours before and         [greater than or
                         after             equal to] 0.5/2 days

Kinbara et al.      NSS 1 mL/kg/h 30          [up arrow] Cr
[111]              minutes before and        [greater than or
                     10 hours after        equal to] 0.5/2 days

Bilasy et al.       NSS 1 mL/kg/h 12          [up arrow] Cr
[112]               hours before and         [greater than or
                         after             equal to] 25%/3 days
                    (In case of CHF          or [up arrow] Cr
                    NSS 0.5 mL/kg/h)         [greater than or
                                           equal to] 0.5/3 days

Abizaid et al.      N/2 1 mL/kg/h 12          [up arrow] Cr
[101]               hours before and         [greater than or
                         after             equal to] 25%/2 days

                                           Incidence of CI-AKI
                 Mean GFR
Authors          Intervention versus       Intervention
                 control                   versus control
                 (mL/min/1.73[m.sup.2])    (%)

Huber et al.        * Cr 2.07 versus            4 versus
[107]                     1.92                     16

Huber et al.        * Cr 1.65 versus            4 versus
[108]                     1.72                     20

Dussol et al.           33 versus              7.5 versus
[33]             38 versus 33 versus 34      6.6 versus 5.2
                                               versus 15.2

Huber et al.        * Cr 1.25 versus            2 versus
[109]               1.25 versus 1.28           12 versus 4

Baskurt et al.       Cr 1.47 versus             0 versus
[110]                1.3 versus 1.39         6.9 versus 9.6

Kinbara et al.         63.4 versus              0 versus
[111]               63.7 versus 62.4          26.7 versus 0

Bilasy et al.          58.6 versus              0 versus
[112]                     61.8                     20

Abizaid et al.       * Cr 1.9 versus            35 versus
[101]                2.3 versus 1.9           30 versus 50

                 Incidence
                 of CI-AKI
Authors                      RRT requirement
                  P value    Intervention versus
                             control (%)

Huber et al.       0.042             ND
[107]

Huber et al.
[108]             0.0138             ND

Dussol et al.       ND            0 versus
[33]                         0 versus 0 versus 0

Huber et al.       0.047             2.7
[109]             0.53 **

Baskurt et al.     0.033          0 versus
[110]                                 0

Kinbara et al.    0.0109          0 versus
[111]                                 0

Bilasy et al.      0.01              ND
[112]

Abizaid et al.      0.6           5 versus
[101]                            0 versus 0

* Mean GFR data is not available. Data is shown
as mean serum creatinine in mg/dL.

** p value of intervention group compare to combination group.
bid: twice daily; CAG: coronary angiography; CHF: congestive
heart failure; CI-AKI: contrast-induced acute kidney injury;
Cr: creatinine; g: gram; D5W: 5% dextrose solution; h: hour;
IV: intravenous; kg: kilogram body weight; mg: milligram;
mL: milliliter; NAC: N-acetylcysteine; ND: no data;
NSS: normal saline solution; N/2: 0.45% NaCl; po: per oral
route; q12h: every 12 hours; RRT: renal replacement therapy.

TABLE 10: Clinical trials comparing nebivolol with placebo
and other agents for prophylaxis of contrast-induced
AKI after angiography.

Authors        Year   Type of procedure    Number of patients
                      and contrast media   Intervention versus
                                           control

Avci et al.    2011          CAG                55 versus
[119]                     Ioxaglate                35

Gunebakmaz     2012          CAG                40 versus
et al. [120]              Iopramide           40 versus 40

                              Study protocol

Authors             Intervention            Control

Avci et al.       Nebivolol 5mg po      Metoprolol 50 mg
[119]           OD 1 week before to     week before to 2
                    2 days after           days after

Gunebakmaz        Nebivolol 5mg po          (1) None
et al. [120]             OD              (2) NAC 600 mg
               1 day before and after        po bid

Authors        Intravascular         CI-AKI definition
               volume expansion
               and NAC protocol

Avci et al.     NSS 1 mL/kg/h 12        [up arrow] Cr
[119]          hours before and 24     [greater than or
                   hours after       equal to] 25%/2 days

Gunebakmaz       NSS 1 mL/kg/h 6        [up arrow] Cr
et al. [120]   hours before and 12     [greater than or
                   hours after        equal to] 25%/2 or
                                     5 days or [up arrow]
                                     Cr [greater than or
                                      equal to] 0.5/2 or
                                            5 days

                                      Incidence of CI-AKI

Authors        Mean GFR
               Intervention versus       Intervention
               control (mL/min/1.73   versus control (%)
               [m.sup.2])

Avci et al.     44.75 versus 43.27        24 versus
[119]                                         33

Gunebakmaz         51.6 versus            20 versus
et al. [120]     47.6 versus 49.8      27.5 versus 22.5

               Incidence
               of CI-AKI

Authors                      RRT requirement
                p value    Intervention versus
                               control (%)

Avci et al.      0.039             ND
[119]

Gunebakmaz       0.72              ND
et al. [120]

* Number of patient data in each group is not available.
Data is shown as total patients in both groups.

** Incidence of CI-AKI for intervention group data
is not available. Data is shown as percentage incidence
of CI-AKI decrease compared to control group. CAG: coronary
angiography; CHF: congestive heart failure; CI-AKI:
contrast-induced acute kidney injury; Cr: creatinine; g: gram; D5W:
5% dextrose solution; h: hour; IV: intravenous; kg: kilogram
body weight; mcg: microgram; mg: milligram; mL: milliliter;
NAC: N-acetylcysteine; ND: no data; NSS: normal saline
solution; N/2: 0.45% NaCl; po: per oral route; q12h:
every 12 hours; RRT: renal replacement therapy;
tid: thrice daily.
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Author:Pattharanitima, Pattharawin; Tasanarong, Adis
Publication:BioMed Research International
Article Type:Report
Date:Jan 1, 2014
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