Open Access

Oral N‑acetylcysteine for prophylaxis of contrast‑induced nephropathy in patients following coronary angioplasty: A meta‑analysis

  • Authors:
    • Jing‑Xiu Li
    • En‑Ze Jin
    • Long‑Hao Yu
    • Yang Li
    • Nan‑Nan Liu
    • Yu‑Mei Dong
    • Xin Li
    • Xue‑Qi Li
  • View Affiliations

  • Published online on: June 27, 2017     https://doi.org/10.3892/etm.2017.4678
  • Pages: 1568-1576
  • Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It is acknowledged that contrast‑induced nephropathy (CIN) is a common cause of acute renal insufficiency after cardiac catheterization and affects mortality and morbidity. To date, it is unknown whether oral N‑acetylcysteine (NAC) is able to prevent contrast‑induced nephropathy (CIN) in patients undergoing coronary angioplasty. A meta‑analysis of randomized controlled trials was performed to assess the effects of NAC in the prevention of CIN in patients following coronary angioplasty. A total of 19 studies published prior to January 2015 that investigated the efficacy of oral NAC for the prevention of CIN were collected from Medline, Cochrane and Embase databases and conference proceedings from cardiology and nephrology meetings. The primary point of investigation was CIN, and the secondary points were renal failure requiring dialysis, mortality and length of hospitalization. The meta‑analysis was performed using fixed‑ or random‑effect models according to heterogeneity. Up to January 2015, 19 randomized placebo‑controlled clinical trials met the inclusion criteria for the meta‑analysis, including 4,514 patients. The pooled data showed that oral NAC did not reduce the CIN incidence [relative risk 0.84, 95% confidence interval (CI) 0.65‑1.10; P=0.20], without heterogeneity among trials (I2=29%). Thus, the present meta‑analysis suggests that oral NAC therapy is not effective as an alternative treatment to prevent CIN in patients following angioplasty. Further high quality randomized clinical controlled trials are required to confirm the usage and availability of this treatment.

Introduction

At present the incidence of contrast-induced nephropathy (CIN) has been increasing in patients undergoing coronary angioplasty, due to the increasing use of contrast media (1). CIN is usually described as an increase in serum creatinine of 0.5 mg/dl or a 25% increase from the baseline value 48 h following the imaging procedure (2). CIN has been reported to occur in ≥14.5% of unselected patients undergoing coronary angioplasty, and is considered to be the third leading cause of hospital-acquired acute renal failure (3). It is more commonly associated with adverse clinical outcomes, increased medical care costs, prolonged hospitalization, and increased in-hospitality morbidity and mortality (4). The major risk factors of CIN are reduced circulation volume, the type and volume of contrast agent, simultaneous administration of nephrotoxic agents and pre-existing renal dysfunction, particularly that due to diabetic nephropathy (58). Since the poor prognosis of patients with diabetic nephropathy could largely attribute to CIN, these patients may benefit greatly from preventive interventions. The precise mechanisms underlying the pathogenesis of CIN have not been well established. However, it is widely speculated that the underlying mechanism of CIN may involve an injury to the renal medulla caused by a combination of reduced blood flow, direct tubular toxicity and an osmotic effect (9). The direct tubular toxicity may be associated with reactive oxygen species (ROS), which are generated following the administration of contrast agent (10). Currently, the preventive treatments for CIN involve reducing contrast exposure, intravenous volume expansion with a saline hydration, and usage of low or iso-osmolarity contrast agent; however, these may provide incomplete prevention of CIN and thus, adjunctive pharmacotherapies in clinical practice have emerged (11). Among these, N-acetylcysteine (NAC) has been of interest since it was initially reported by Tepel et al (12). NAC as a direct scavenger of free radicals may improve blood flow via nitric oxide-mediated pathways, and it is a precursor of glutathione synthesis, providing vasodilation and antioxidant activity against CIN (13). Therefore, oral NAC therapy may be an alternative method for CIN prevention, providing safety, low cost and few side effects (14).

It has been reported that oral NAC may more effectively provide protection against CIN compared with intravenous hydration alone (15). Results of the initial study (12) of oral NAC for the prevention of CIN were encouraging, while the bioavailability of oral NAC may be low and exhibited mixed results; a few trials demonstrated the reduction of CIN incidence by oral NAC therapy (1621), and most trials revealed no significant CIN prevention (2234). The aim of the present study was to determine whether oral NAC therapy is beneficial for CIN prevention in clinical practice, using a meta-analysis.

Materials and methods

Search strategy and selection criteria

A comprehensive study was performed to search all published randomized controlled trials (RCT) until January 1, 2015 which concerned oral NAC treatment to prevent CIN in patients undergoing coronary angioplasty, using searching engines such as Medline (https://www.nlm.nih.gov/bsd/pmresources.html), Embase (https://www.elsevier.com/solutions/embase-biomedical-research) and Cochrane (http://uk.cochrane.org/). The search terms were as follows: N-acetylcysteine, acetylcysteine, NAC, cardiac catheterization, coronary angioplasty, coronary angiogram, percutaneous coronary intervention, contrast-induced nephropathy, contrast-induced nephrotoxicity, contrast-medium nephrotoxicity, contrast medium-induced nephropathy and contrast-induced acute kidney injury. RCTs were limited to those with human subjects. A manual search of the results was then performed for the qualifying trials. Abstracts alone or meeting proceedings were excluded. This search strategy was performed comprehensively until no new potential citations were found on review of the reference list of retrieved papers. All of the studies published in English which met the following inclusion criteria were included: Subjects underwent coronary angioplasty, randomization of oral NAC and placebo, and data regarding CIN incidence. Exclusion criteria were as follows: <18 years of age, known allergy or hypersensitivity to NAC, dialysis patients and those with ST-segment elevation myocardial infarction undergoing primary angioplasty.

Data extraction and quality assessment

Two investigators (Dr Jing-Xiu Li and Dr Nan-Nan Liu) were assigned independently to assemble the information of each study as follows: First author name, surgery type (coronary angiography or percutaneous coronary intervention), study design (RCT, prospective or not), control types (placebo or not), blinding types (double-blinding or not), NAC regimen, sample size, mean age, percentage of males, the incidence of CIN and length of hospitalization in each group. Disagreements were settled through discussion and consensus.

Risk of bias

The majority of selected trials were conducted in randomized sequence generation and allocation concealment, and the participants were divided randomly. All of them were considered to be of low bias risk.

Statistical analysis

The relative risk (RR) was estimated with 95% confidence interval (CI) for dichotomous outcomes. Heterogeneity was reported with the I2 statistic, using a fixed-effects model, and >50% of I2 was considered to be statistically significant. Begg and Egger tests were performed for presenting the publication bias, and the potential bias was analyzed with visual inspection of the Begg funnel plots in which the log RRS plotted against their standard errors. P<0.05 was considered to indicate a statistically significant difference. All statistical analyses were performed using STATA software, version 12.0 (StataCorp LP, College Station, TX, USA) and RevMan 5.2 (The Nordic Cochrane Centre, Copenhagen, Denmark).

Results

Description of the studies

A total of 19 placebo-control RCTs were included in this study, consisting of 4,514 patients. The flow of identified studies through the selection process is shown in Fig. 1. The characteristics at baseline and design of the selected studies are shown in Tables I and II. The range of participant number was 36–2,308, including men and women. The range of total NAC dosage was 1,200–12,000 mg. The effects of oral NAC on CIN prevention were also compared.

Table I.

Characteristic data of studies included in the meta-analysis.

Table I.

Characteristic data of studies included in the meta-analysis.

Authors, yearPatients (I/C)Renal function for inclusion (mg/dl)CIN definition (SCr)Contrast agentAvg. contrast volume (ml)Hydration regimenCumulative NAC dose (mg)Diabetes mellitus (%)Refs.
Ochoa et al, 200480 (36/44)>1.8 (male) >1.6 (female)0.5 mg/dl or ≥25% aboveLow osmolarity1550.9% saline 1,500 ml1,000 (1 h before and 4 h after)55(16)
MacNeill et al, 200343 (21/22)>1.5≥25% above baseline after 72 hLow osmolarity1030.45% 1 ml/kg/h600 (bid for 4 doses)46.50(17)
Briguori et al, 2002183 (92/91)>1.2≥25% above baseline after 48 hLow osmolarity1400.45% 1 ml/kg/h600 (bid pre/post)37.70(18)
Diaz-Sandoval et al, 200254 (25/29)>1.40.5 mg/dl or ≥25% aboveLow osmolarity1890.45% 1 ml/kg/h 2.12 h before, 12 h after600 bid for 4 doses38.90(19)
Kay et al, 2003200 (102/98)>1.2 mg/dl≥25% above baseline within 48 hLow osmolarity1200.9% 1 ml/kg/h 12 h before, 6 h after600 (PO bid pre/post)37.50(20)
Shyu et al, 2002121 (60/61)>2.0 mg/dl0.5 mg/dl after 48 hLow osmolarity1190.45% 1 ml/kg/h 12 h before, 12 h after400 (PO bid pre/post)63.60(21)
ACT Investigators, 20112,308 (1,172/1,136)>1.50.5 mg/dl 48.96 hHigh osmolarity Low osmolarity Iso-osmolar1000.9% 1 ml/kg/h 6.12 h before, 6.12 h after1,200 (bid pre/post)68.45(22)
Allaqaband et al, 200285 (45/40)>1.60.5 mg/dl after 48 hLow osmolarity1220.45% 1 ml/kg/h 12 h before, 12 h after600 (bid pre/post)48.29(23)
Amini et al, 200990 (45/45)>1.50.5 mg/dl or ≥25% above baseline after 48 hLow osmolarity Iso-osmolar1180.9% saline 1,000 ml600 (bid pre/post)N/A(24)
Baskurt et al, 2009145 (73/72)>1.30.5 mg/dl or ≥25% above baseline after 48 hLow osmolarity1130.9% 1 ml/kg/h 12 h before, 12 h after600 (bid pre/post)30.34(25)
Oldemeyer et al, 200396 (49/47)>1.20.5 mg/dl or ≥25% above baseline after 48 hLow osmolarity1340.45% 1 ml/kg/h 12 h before, 12 h after1,500 (bid for 4 doses)44.79(26)
Durham et al, 200279 (41/38)>1.70.5 mg/dl after 48 hLow osmolarity840.45% 1 ml/kg/h 12 h before, 12 h after1,200 bid pre/post48.10(27)
Ferrario et al, 2009200 (99/101)>1.50.5 mg/dl or ≥25% above baseline within 72 hIso-osmolar1800.9% 1 ml/kg/h 12.24 h before, 24 h after600 (bid pre/post)25(28)
Fung et al, 200491 (46/45)>1.50.5 mg/dl after 48 hLow osmolarity1350.9% saline 100 ml/h 12 h before, 12 h after600 (PO, thrice pre/post)52.74(29)
Goldenberg et al, 200480 (41/39)>1.50.5 mg/dl after 48 hLow osmolarity1110.45% 1 ml/kg/h 12 h before, 12 h after600 (PO, thrice pre/post43.75(30)
Gomes et al, 2005156 (77/79)>1.20.5 mg/dl after 48 hLow osmolarity1020.9% 1 ml/kg/h 12 h before, 12 h after600 (PO, bid pre/post51.90(31)
Kimmel et al, 200836 (19/17)>1.20.5 mg/dl or ≥25% above baselineLow osmolarity2190.45% 1 ml/kg/h 12 h before, 12 h after600 (PO, bid pre/post)30.60(32)
Ozcan et al, 2007176 (88/88)>1.20.5 mg/dl or ≥25% above baseline after 48 hLow osmolarity1100.9% 1 ml/kg/h 6 h before, 6 h after600 (PO, bid pre/post)46.60(33)
Yang et al, 2014318 (157/161)N/A≥25% above baseline within 72 hLow osmolarity1240.9% 1.5 ml/kg/h 6 h before, 6 h after600 (PO, bid pre/post)25.50(34)

[i] 1 mg/dl=88.4 µmol/l. I/C, interventions/controls; CIN, contrast-induced nephropathy; SCr, serum creatinine; NAC, N-acetylcysteine; N/A, data not available; bid, bis in die (twice a day); PO, oral.

Table II.

Baseline and difference in SCr.

Table II.

Baseline and difference in SCr.

CIN (%)Acetylcysteine SCr (mg/dl)Control SCr (mg/dl)



Author, yearAcetylcysteineControlBaselineSecond SCrBaselineSecond SCrRefs.
Ochoa et al, 2004325   2.02±0.56   2.10±0.81   1.93±0.53   2.10±0.74(16)
MacNeill et al, 2003532   1.89±0.38   1.90±0.36   1.88±0.41   2.14±0.87(17)
Briguori et al, 20026.50111.54±0.4   1.48±0.36   1.5±0.4   1.53±0.45(18)
Diaz-Sandoval et al, 2002845   1.66±0.06   1.53±0.09   1.56±0.05   1.88±0.09(19)
Kay et al, 20034121.35   1.22   1.36   1.38(20)
Shyu, et al, 20023.3024.60   2.8±0.8   2.5±1.0   2.8±0.8   3.1±1.0(21)
ACT Investigators, 201112.7012.70   1.2±0.5   N/A   1.2±0.5   N/A(22)
Allaqaband et al, 200217.7015.30   2.2±0.73   2.22±1.00   2.03±0.79   2.03±0.48(23)
Amini et al, 200911.1014.301.736±0.422.083±0.41.736±0.172.185±0.1(24)
Baskurt et al, 2009106.90   1.39±0.24   1.47±0.38   1.3±0.20   1.38±0.34(25)
Oldemeyer et al, 20038.206.40   1.63±0.81   N/A   1.66±0.65   N/A(26)
Durham et al, 200226.3022   2.3±0.5   N/A   2.2±0.4   N/A(27)
Ferrario et al, 20098.105.9N/A   N/AN/A   N/A(28)
Fung et al, 200417.4013.30   2.27±0.54   2.45±0.65   2.37±0.61   2.40±0.70(29)
Goldenberg et al, 2004108   2.0±0.4   N/A   1.9±0.3   N/A(30)
Gomes et al, 200510.4010.10N/A   N/A   N/A   N/A(31)
Kimmel et al, 20085.305.90   1.51±0.23   N/A   1.65±0.65   N/A(32)
Ozcan et al, 200712.5013.601.4   1.42   1.4   1.46(33)
Yang et al, 20144.463.11N/A   N/A   N/A   N/A(34)

[i] CIN, contrast-induced nephropathy; SCr, serum creatinine; N/A, data not available.

Quality assessment of the trials and publication bias

The selected trials in the meta-analysis were well-designed and reasonably conducted, adequately implementing randomized sequence generation and allocation concealment. The participants among them were blinded. All of the selected studies had a low risk of bias, and the details are shown in Fig. 2. Publication bias assessed by Egger's test is shown in Fig. 3.

CIN incidence

The baseline characteristics revealed no significant difference between history of coexistent disease and routine prophylactic therapies. The CIN incidence was 247 patients in the oral NAC group (n=2,269) and 278 patients in the control group (n=2,245), pooling all of the 19 trials. There was no statistical significance (RR, 0.84; 95% CI, 0.65–1.10; P=0.20, Fig. 4), with no heterogeneity between trials (I2=29%, P=0.12).

Discussion

In this meta-analysis, 19 RCTs were combined in order to evaluate the effects of oral NAC on CIN prevention in patients undergoing coronary angioplasty. The results showed that oral NAC treatment was not associated with a reduction of CIN incidence, and there was no significant heterogeneity between trials. In addition, it was found that the combined treatments of oral NAC and sodium chloride did not provide additional benefits; therefore, the role of oral NAC therapy is yet to be defined in CIN prevention (11,35,36).

It has been reported that contrast-induced nephropathy occurred in ~14.5% of unselected patients following coronary angioplasty. CIN has been considered as the third common cause of in-hospital acute renal failure after coronary angiography/intervention (37). In present studies, the commonly accepted standard for CIN is according to the absolute or relative change in plasma creatinine concentration (38). In the majority of cases, CIN is defined as an increase in baseline serum creatinine (SCr) concentration of 25% or an absolute increase of at least 44 mmol/l within 48 h (39). It is universally acknowledged that absolute increase in SCr is superior threshold than a relative increase in SCr (4043). However, it has been shown that SCr may not be an optimal substitute marker for glomerular filtration rate (GFR), as the alteration in renal handling, filtration, secretion and resorption may exert an influence on SCr levels (44). As has been noted previously (45), tubular creatinine secretion may be decreased by contrast media itself. Thus, it may cause a transient increase in SCr concentration, independent of the reduction in GFR. Serum cystatin C has been proposed as a sensitive biomarker for the diagnosis of CIN, as cystatin C has been confirmed to reflect contrast medium-induced deterioration in kidney function in a superior manner to serum creatinine (46). A previous study showed that oral NAC did not significantly reduce the incidence of CIN on the basis of the standard disease definition; however, by the cystatin C level disease criteria it may be considered to be efficacious (47). However, at present SCr remains the cheapest and most widely accepted standard of renal function (48). Therefore, the change of absolute or relative SCr concentration remains a key parameter in the diagnosis of CIN. Intravenous saline hydration and the use of low-osmolality contrast medium has been accepted as preventive strategies for CIN (4951).

In the present meta-analysis, 19 placebo-control RCTs were included, consisting of 4,514 patients. The baseline characteristic revealed no significant difference between history of coexistent disease and routine prophylactic therapies. Each randomize controlled trial utilized intravenous saline hydration. The CIN incidence was 247 patients in the oral NAC group (n=2,269) and 278 patients in the control group (n=2,245), pooling all of the 19 trials. There was no statistically significant difference between the oral NAC group and the control group (RR, 0.84; 95% CI, 0.65–1.10; P=0.20), with no heterogeneity between trials (I2=29%, P=0.12). The results showed that the oral NAC treatment was not associated with a reduction in CIN incidence. A previous study (52) found that intravenous saline hydration with 0.45% saline prior to and following coronary angiography and the proper use of nonionic low osmolar iodine may be renoprotective. Previously, it has been confirmed (51) that normal saline hydration (0.9%) may be more efficacious compared with half-normal saline (0.45%). It is generally accepted that the optimal volume of normal saline hydration may be determined based on body weight, and 1.0–1.5 ml/kg/h is considered to be the normal range (39). In the present meta-analysis, it was found that the combined treatments of oral NAC and sodium chloride did not provide additional benefits, and thus the role of oral NAC therapy not yet to be defined in CIN prevention.

The precise mechanism underlying the pathogenesis of CIN remains unclear. It is widely considered (5355) that the pathogenesis of CIN may involve injury to the renal medulla caused by reduced renal blood flow and tubular toxicity through ROS, which occurs following the administration of contrast media (1,56). NAC, a thiol-containing antioxidant, has been approved for an increase in the level of plasma glutathione, which is an oxygen-free radical scavenger (13). It has been affirmed (57) that NAC is able to prevent oxidative stress at the location of renal post-ischemia. NAC has received considerable attention in recent years following research by Tepel et al (12). In the opinion of Tepel et al, the utilization of NAC in conjunction with a fixed volume (75 ml) of low-osmolar contrast medium in patients undergoing computed tomography (CT), may significantly reduce incidence of CIN. It has become increasing recognized that NAC may result in increased nitric oxide production and intensification of nitric oxide binding (58). It has been demonstrated in human testing (59) that NAC treatment may significantly improve endothelium-dependent vasodilation. In a previous study, it was found that pretreatment of vascular smooth muscle cells with NAC clearly reduced ROS formation and prevented the reduction of cell viability (60). In the present meta-analysis, the majority of the selected trials utilized a low dose of NAC (600 mg) twice daily for 48 h in conjunction with intravenous saline hydration. It is known the oral NAC may be absorbed quickly, reaching the peak plasma concentration in 45 min, and having a half-life of 2 h. Thus, pretreatment with NAC more than a few hours prior to contrast exposure or for a prolonged period afterward may not be essential to provide beneficial effects.

There were a number of limitations inherent to this study. First, the asymmetrical appearance of the funnel plot suggests that publication bias was present. Despite the broad searching databases and manually searching the conference proceedings and reference lists from the identified trials, we could not eliminate that publication bias caused overestimation of the results from the true treatment. Second, all included studies used the endpoint of CIN as the primary outcome. Typically, this has been defined as an increase in baseline serum creatinine level of 25% or an absolute increase of 44 mmol/l. It found that NAC had no effect on preventing CIN on the basis of the standard diagnostic definition, while it showed a preventive effect based on cystatin C levels. Whether a newer urinary biomarker such as cystatin C may identify kidney damage for CIN requires further research. Finally, despite earlier studies having shown the association of CIN with increased in-hospital morbidity and mortality, particularly in patients that require dialysis, insufficient trials have been designed to investigate the effect of NAC on these clinical relevant outcomes. Thus, the present study did not identify sufficient evidence for a meta-analysis to assess the effect of NAC on these relatively rare, but key outcomes.

This meta-analysis of 19 placebo-controlled RCTs indicated that oral NAC did not significantly reduce the incidence of CIN. Also, it revealed that the combination of oral NAC and sodium chloride may not provide additional benefits compared with hydration with sodium chloride alone. Up to now, trials are too inconsistent to warrant a conclusion on efficacy. Recently, it has been found that oral NAC is able to confer a preventive effect of CIN based on cystatin C. Therefore, further high quality RCTs are required to confirm the safety and investigate the effect of oral NAC on clinically relevant outcomes, such as in-hospital morbidity, mortality and cost of medical care, particularly in patients that require dialysis.

Acknowledgements

The present study was supported by the Science Fund for Distinguished Young Scholars of the Fourth Affiliated Hospital of Harbin Medical University (grant no. HYDSYJQ201504).

References

1 

Tepel M, Aspelin P and Lameire N: Contrast-induced nephropathy: A clinical and evidence-based approach. Circulation. 113:1799–1806. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Thomsen HS: European Society of Urogenital Radiology (ESUR) guidelines on the safe use of iodinated contrast media. Eur J Radiol. 60:307–313. 2006. View Article : Google Scholar : PubMed/NCBI

3 

McCullough PA, Wolyn R, Rocher LL, Levin RN and O'Neill WW: Acute renal failure after coronary intervention: Incidence, risk factors, and relationship to mortality. Am J Med. 103:368–375. 1997. View Article : Google Scholar : PubMed/NCBI

4 

Rihal CS, Textor SC, Grill DE, Berger PB, Ting HH, Best PJ, Singh M, Bell MR, Barsness GW, Mathew V, et al: Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation. 105:2259–2264. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Nikolsky E, Mehran R, Turcot D, Aymong ED, Mintz GS, Lasic Z, Lansky AJ, Tsounias E, Moses JW, Stone GW, et al: Impact of chronic kidney disease on prognosis of patients with diabetes mellitus treated with percutaneous coronary intervention. Am J Cardiol. 94:300–305. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Bartholomew BA, Harjai KJ, Dukkipati S, Boura JA, Yerkey MW, Glazier S, Grines CL and O'Neill WW: Impact of nephropathy after percutaneous coronary intervention and a method for risk stratification. Am J Cardiol. 93:1515–1519. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Mehran R, Aymong ED, Nikolsky E, Lasic Z, Iakovou I, Fahy M, Mintz GS, Lansky AJ, Moses JW, Stone GW, et al: A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: Development and initial validation. J Am Coll Cardiol. 44:1393–1399. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Parfrey PS, Griffiths SM, Barrett BJ, Paul MD, Genge M, Withers J, Farid N and McManamon PJ: Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study. N Eng J Med. 320:143–149. 1989. View Article : Google Scholar

9 

Rudnick MR and Goldfarb S: Pathogenesis of contrast-induced nephropathy: Experimental and clinical observations with an emphasis on the role of osmolality. Rev Cardiovasc Med. 4 Suppl 5:S28–S33. 2003.PubMed/NCBI

10 

Murphy SW, Barrett BJ and Parfrey PS: Contrast nephropathy. J Am Soc Nephrol. 11:177–182. 2000.PubMed/NCBI

11 

Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE Jr, Ettinger SM, Fesmire FM, Ganiats TG, Jneid H, Lincoff AM, et al: 2011 ACCF/AHA focused update of the Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction (Updating the 2007 Guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American College of Emergency Physicians, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 59:1920–1959. 2011. View Article : Google Scholar

12 

Tepel M, van der Giet M, Schwarzfeld C, Laufer U, Liermann D and Zidek W: Prevention of radiographic-contrast-agent-induced reductions in renal function by acetylcysteine. N Engl J Med. 343:180–184. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Shalansky SJ, Vu T, Pate GE, Levin A, Humphries KH and Webb JG: N-acetylcysteine for prevention of radiographic contrast material-induced nephropathy: Is the intravenous route best? Pharmacotherapy. 25:1095–1103. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Karimzadeh I, Khalili H, Sagheb MM and Farsaei S: A double-blinded, placebo-controlled, multicenter clinical trial of N-acetylcysteine for preventing amphotericin B-induced nephrotoxicity. Expert Opin Drug Metab Toxicol. 11:1345–1355. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Baker CS, Wragg A, Kumar S, De Palma R, Baker LR and Knight CJ: A rapid protocol for the prevention of contrast induced renal dysfunction: The RAPPID study. J Am Coll Cardiol. 41:2114–2118. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Ochoa A, Pellizzon G, Addala S, Grines C, Isayenko Y, Boura J, Rempinski D, O'Neill W and Kahn J: Abbreviated dosing of N-acetylcysteine prevents contrast-induced nephropathy after elective and urgent coronary angiography and intervention. J Interv Cardiol. 17:159–165. 2004. View Article : Google Scholar : PubMed/NCBI

17 

MacNeill BD, Harding SA, Bazaril H, Patton KK, Colon-Hernadez P, DeJoseph D and Jang IK: Prophylaxis of contrast-induced nephropathy in patients undergoing coronary angiography. Catheter Cardiovasc Interv. 60:458–461. 2003. View Article : Google Scholar : PubMed/NCBI

18 

Briguori C, Manganelli F, Scarpato P, Elia PP, Golia B, Riviezzo G, Lepore S, Librera M, Villari B, Colombo A and Ricciardelli B: Acetylcysteine and contrast agent associated nephrotoxicity. J Am Coll Cardiol. 40:298–303. 2002. View Article : Google Scholar : PubMed/NCBI

19 

Diaz-Sandoval LJ, Kosowsky BD and Losordo DW: Acetylcysteine to prevent angiography-related renal tissue injury (the APART trial). Am J Cardiol. 89:356–358. 2002. View Article : Google Scholar : PubMed/NCBI

20 

Kay J, Chow WH, Chan TM, Lo SK, Kwok OH, Yip A, Fan K, Lee CH and Lam WF: Acetylcysteine for prevention of acute deterioration of renal function following elective coronary angiography and intervention: A randomized controlled trial. JAMA. 289:553–558. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Shyu KG, Cheng JJ and Kuan P: Acetylcysteine protects against acute renal damage in patients with abnormal renal function undergoing a coronary procedure. J Am Coll Cardiol. 40:1383–1388. 2002. View Article : Google Scholar : PubMed/NCBI

22 

ACT Investigators, . Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascularangiography: Main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT). Circulation. 124:1250–1259. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Allaqaband S, Tumuluri R, Malik AM, Gupta A, Volkert P, Shalev Y and Bajwa TK: Prospective randomized study of N-acetylcysteine, fenoldopam and saline for prevention of radiocontrast-induced nephropathy. Catheter Cardiovasc Interv. 57:279–283. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Amini M, Salarifar M, Amirbaigloo A, Masoudkabir F and Esfahani F: N-acetylcysteine does not prevent contrast-induced nephropathy after cardiac catheterization in patients with diabetes mellitus and chronic kidney disease: A randomized clinical trial. Trials. 10:452009. View Article : Google Scholar : PubMed/NCBI

25 

Baskurt M, Okcun B, Abaci O, Dogan GM, Kilickesmez K, Ozkan AA, Ersanli M and Gurmen T: N-acetylcysteine versus N-acetylcysteine+theophylline for the prevention of contrast nephropathy. Eur J Clin Invest. 39:793–179. 2009. View Article : Google Scholar : PubMed/NCBI

26 

Oldemeyer JB, Biddle WP, Wurdeman RL, Mooss AN, Cichowski E and Hilleman DE: Acetylcysteine in the prevention of contrast induced nephropathy after coronary angiography. Am Heart J. 146:E232003. View Article : Google Scholar : PubMed/NCBI

27 

Durham JD, Caputo C, Dokko J, Zaharakis T, Pahlavan M, Keltz J, Dutka P, Marzo K, Maesaka JK and Fishbane S: A randomized controlled trial of N-acetylcysteine to prevent contrast nephropathy in cardiac angiography. Kidney Int. 62:2202–2207. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Ferrario F, Barone MT, Landoni G, Genderini A, Heidemperger M, Trezzi M, Piccaluga E, Danna P and Scorza D: Acetylcysteine and non-ionic isosmolar contrast-induced nephropathy - a randomized controlled study. Nephrol Dial Transplant. 24:3103–3107. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Fung JW, Szeto CC, Chan WW, Kum LC, Chan AK, Wong JT, Wu EB, Yip GW, Chan JY, Yu CM, et al: Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: A randomized trial. Am J Kidney Dis. 43:801–808. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Goldenberg I, Shechter M, Matetzky S, Jonas M, Adam M, Pres H, Elian D, Agranat O, Schwammenthal E and Guetta V: Oral acetylcysteine as an adjunct to saline hydration for the prevention of contrast-induced nephropathy following coronary angiography. A randomized controlled trial and review of the current literature. Eur Heart J. 25:212–218. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Gomes VO, de Figueredo CE Poli, Caramori P, Lasevitch R, Bodanese LC, Araújo A, Röedel AP, Caramori AP, Brito FS Jr, Bezerra HG, et al: N-acetylcysteine does not prevent contrast induced nephropathy after cardiac catheterisation with an ionic low osmolality contrast medium: A multicentre clinical trial. Heart. 91:774–778. 2005. View Article : Google Scholar : PubMed/NCBI

32 

Kimmel M, Butscheid M, Brenner S, Kuhlmann U, Klotz U and Alscher DM: Improved estimation of glomerular filtration rate by serum cystatin C in preventing contrast induced nephropathy by N-acetylcysteine or zinc - preliminary results. Nephrol Dial Transplant. 23:1241–1245. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Ozcan EE, Guneri S, Akdeniz B, Akyildiz IZ, Senaslan O, Baris N, Aslan O and Badak O: Sodium Bicarbonate, N-acetylcysteine and saline for prevention of radiocontrast-induced nephropathy. A comparison of 3 regimens for protecting contrast-induced nephropathy in patients undergoing coronary procedures. A single-center prospective controlled trial. Am Heart J. 154:539–544. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Yang K, Liu W, Ren W and Lv S: Different interventions in preventing contrast-induced nephropathy after percutaneous coronary intervention. Int Urol Nephrol. 46:1801–1807. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS, European Association for Percutaneous Cardiovascular Interventions (EAPCI), ; Wijns W, Kolh P, Danchin N, Di Mario C, Falk V, Folliguet T, Garg S, Huber K, et al: Guidelines on myocardial revascularization. Eur Heart J. 31:2501–2555. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Stephan Windecker, Kolh P, Alfonso F, Collet JP, Cremer J, Falk V, Filippatos G, Hamm C, Head SJ, Jüni P, et al: 2014 ESC/EACTS guidelines on myocardial revascularization. Rev Esp Cardiol (Engl Ed). 68:1442015.PubMed/NCBI

37 

Nash K, Hafeez A and Hou S: Hospital-acquired renal insufficiency. Am J Kidney Dis. 39:930–936. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Morcos SK, Thomsen HS and Webb JA: Contrast-media-induced nephrotoxicity: A consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). Eur Radiol. 9:1602–1613. 1999. View Article : Google Scholar : PubMed/NCBI

39 

Stacul F, van der Molen AJ, Reimer P, Webb JA, Thomsen HS, Morcos SK, Almén T, Aspelin P, Bellin MF, Clement O, et al: Contrast induced nephropathy: Updated ESUR contrast media safety committee guidelines. Eur Radiol. 21:2527–2541. 2011. View Article : Google Scholar : PubMed/NCBI

40 

Waikar SS and Bonventre JV: Creatinine kinetics and the definition of acute kidney injury. J Am Soc Nephrol. 20:672–679. 2009. View Article : Google Scholar : PubMed/NCBI

41 

Thomsen HS and Morcos SK: Risk of contrast-medium-induced nephropathy in high-risk patients undergoing MDCT - a pooled analysis of two randomized trials. Eur Radiol. 19:891–897. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Reddan D, Laville M and Garovic VD: Contrast-induced nephropathy and its prevention: What do we really know from evidence-based findings? J Nephrol. 22:333–351. 2009.PubMed/NCBI

43 

Toprak O: What is the best definition of contrast-induced nephropathy? Ren Fail. 29:387–388. 2007. View Article : Google Scholar : PubMed/NCBI

44 

Ma YC, Zuo L, Chen JH, Luo Q, Yu XQ, Li Y, Xu JS, Huang SM, Wang LN, Huang W, et al: Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol. 17:2937–2944. 2006. View Article : Google Scholar : PubMed/NCBI

45 

Bräutigam M and Persson PB: Do iodinated contrast media interfere with renal tubular creatinine secretion? Radiology. 240:6152006. View Article : Google Scholar : PubMed/NCBI

46 

Sun Z, Fu Q, Cao L, Jin W, Cheng L and Li Z: Intravenous N-acetylcysteine for prevention of contrast-induced nephropathy: A meta-analysis of randomized, controlled trials. PLoS One. 8:e551242013. View Article : Google Scholar : PubMed/NCBI

47 

Kim BJ, Sung KC, Kim BS, Kang JH, Lee KB, Kim H and Lee MH: Effect of N-acetylcysteine on cystatin C-based renal function after elective coronary angiography (ENABLE Study): A prospective, randomized trial. Int J Cardiol. 138:239–245. 2010. View Article : Google Scholar : PubMed/NCBI

48 

Molitoris BA, Levin A, Warnock DG, Joannidis M, Mehta RL, Kellum JA, Ronco C and Shah SV; Acute Kidney Injury Network working group, : Improving outcomes of acute kidney injury: report of an initiative. Nat Clin Pract Nephrol. 3:439–442. 2007. View Article : Google Scholar : PubMed/NCBI

49 

Chen Y, Hu S, Liu Y, Zhao R, Wang L, Fu G, He Q, Su X, Zheng Y, Qi X, et al: Renal tolerability of iopromide and iodixanol in 562 renally impaired patients undergoing cardiac catheterisation: The DIRECT study. EuroIntervention. 8:830–838. 2012. View Article : Google Scholar : PubMed/NCBI

50 

Stacul F, Adam A, Becker CR, Davidson C, Lameire N, McCullough PA and Tumlin J; CIN Consensus Working Panel, : Strategies to reduce the risk of contrast-induced nephropathy. Am J Cardiol. 98:59K–77K. 2006. View Article : Google Scholar : PubMed/NCBI

51 

Mueller C, Buerkle G, Buettner HJ, Petersen J, Perruchoud AP, Eriksson U, Marsch S and Roskamm H: Prevention of contrast media-associated nephropathy: randomized comparison of 2 hydration regimens in 1620 patients undergoing coronary angioplasty. Arch Intern Med. 162:329–336. 2002. View Article : Google Scholar : PubMed/NCBI

52 

Erley CM, Duda SH, Rehfuss D, Scholtes B, Bock J, Müller C, Osswald H and Risler T: Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline. Nephrol Dial Transplant. 14:1146–1149. 1999. View Article : Google Scholar : PubMed/NCBI

53 

Sendeski M, Patzak A and Persson PB: Constriction of the vasa recta, the vessels supplying the area at risk for acute kidney injury, by four different iodinated contrast media, evaluating ionic, nonionic, monomeric and dimeric agents. Invest Radiol. 45:453–457. 2010. View Article : Google Scholar : PubMed/NCBI

54 

Seeliger E, Sendeski M, Rihal CS and Persson PB: Contrast-induced kidney injury: Mechanisms, risk factors, and prevention. Eur Heart J. 33:2007–2015. 2012. View Article : Google Scholar : PubMed/NCBI

55 

Seeliger E, Lenhard DC and Persson PB: Contrast media viscosity versus osmolality in kidney injury: Lessons from animal studies. Biomed Res Int. 2014:3581362014. View Article : Google Scholar : PubMed/NCBI

56 

Parfrey P: The clinical epidemiology of contrast-induced nephropathy. Cardiovasc Intervent Radiol. 28 Suppl 2:S3–S11. 2005. View Article : Google Scholar : PubMed/NCBI

57 

Kiefer P, Vogt J and Radermacher P: From mucolytic to antioxidant and liver protection: New aspects in the intensive care unit career of N-acetylcysteine. Crit Care Med. 28:3935–3936. 2000. View Article : Google Scholar : PubMed/NCBI

58 

Efrati S, Dishy V, Averbukh M, Blatt A, Krakover R, Weisgarten J, Morrow JD, Stein MC and Golik A: The effect of N-acetylcysteine on renal function, nitric oxide, and oxidative stress after angiography. Kidney Int. 64:2182–2187. 2003. View Article : Google Scholar : PubMed/NCBI

59 

Quintavalle C, Brenca M, De Micco F, Fiore D, Romano S, Romano MF, Apone F, Bianco A, Zabatta MA, Troncone G, et al: In vivo and in vitro assessment of pathways involved in contrast media-induced renal cells apoptosis. Cell Death Dis. 2:e1552011. View Article : Google Scholar : PubMed/NCBI

60 

Li JX, Shen YQ, Cai BZ, Zhao J, Bai X, Lu YJ and Li XQ: Arsenic trioxide induces the apoptosis in vascular smooth muscle cells via increasing intracellular calcium and ROS formation. Mol Biol Rep. 37:1569–1576. 2010. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

August-2017
Volume 14 Issue 2

Print ISSN: 1792-0981
Online ISSN:1792-1015

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Li JX, Jin EZ, Yu LH, Li Y, Liu NN, Dong YM, Li X and Li XQ: Oral N‑acetylcysteine for prophylaxis of contrast‑induced nephropathy in patients following coronary angioplasty: A meta‑analysis. Exp Ther Med 14: 1568-1576, 2017
APA
Li, J., Jin, E., Yu, L., Li, Y., Liu, N., Dong, Y. ... Li, X. (2017). Oral N‑acetylcysteine for prophylaxis of contrast‑induced nephropathy in patients following coronary angioplasty: A meta‑analysis. Experimental and Therapeutic Medicine, 14, 1568-1576. https://doi.org/10.3892/etm.2017.4678
MLA
Li, J., Jin, E., Yu, L., Li, Y., Liu, N., Dong, Y., Li, X., Li, X."Oral N‑acetylcysteine for prophylaxis of contrast‑induced nephropathy in patients following coronary angioplasty: A meta‑analysis". Experimental and Therapeutic Medicine 14.2 (2017): 1568-1576.
Chicago
Li, J., Jin, E., Yu, L., Li, Y., Liu, N., Dong, Y., Li, X., Li, X."Oral N‑acetylcysteine for prophylaxis of contrast‑induced nephropathy in patients following coronary angioplasty: A meta‑analysis". Experimental and Therapeutic Medicine 14, no. 2 (2017): 1568-1576. https://doi.org/10.3892/etm.2017.4678