Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial

doi:10.1053/j.ajkd.2004.01.010

American Journal of Kidney Diseases

Volume 43, Issue 5, May 2004, Pages 801-808

https://doi.org/10.1053/j.ajkd.2004.01.010 Get rights and content

Abstract

Background: The effect of N-acetylcysteine (NAC) to prevent contrast nephropathy (CN) in patients with moderate to severe renal insufficiency undergoing coronary angiography or interventions is not clear. Methods: This is a prospective, open-label, randomized, controlled trial. Ninety-one consecutive patients with a serum creatinine level of 1.69 to 4.52 mg/dL (149 to 400 μmol/L) undergoing coronary procedures were recruited and randomly assigned to administration of either oral NAC, 400 mg, thrice daily the day before and day of the contrast procedure (the NAC group) or no drug (the control group). Serum creatinine was measured before and 48 hours after contrast exposure. The primary end point of this study was the development of CN, defined as an increase in serum creatinine concentration of 0.5 mg/dL or greater (≥44 μmol/L) or a reduction in estimated glomerular filtration rate (GFR) of 25% or greater of the baseline value 48 hours after the procedure. Results: There were no significant differences between the 2 groups (46 patients, NAC group; 45 patients, control group) in baseline characteristics or mean volume of contrast agent administered. Six patients (13.3%) in the control group and 8 patients (17.4%) in the NAC group developed CN (P = 0.8). Serum creatinine levels increased from 2.27 ± 0.54 to 2.45 ± 0.65 mg/dL (201 ± 48 to 217 ± 57 μmol/L; P = 0.003) in the NAC group and 2.37 ± 0.61 to 2.40 ± 0.70 mg/dL (210 ± 54 to 212 ± 62 μmol/L; P = 0.6) in the control group. The increase in serum creatinine levels between the 2 groups had no difference (P = 0.7). Estimated GFR decreased from 30.3 ± 8.4 to 28.1 ± 8.4 mL/min (P = 0.01) in the NAC group and 28.4 ± 8.6 to 27.5 ± 8.8 mL/min (P = 0.3) in the control group. The decline in estimated GFR between the 2 groups had no difference (P = 0.7). Conclusion: In the current study, oral NAC had no effect on the prevention of CN in patents with moderate to severe renal insufficiency undergoing coronary angiography or interventions. However, the sample size of our present study is small. Our findings highlight the need for a large-scale, randomized, controlled trial to determine the exact beneficial effect of NAC.

Section snippets

Methods

We enrolled consecutive patients with a serum creatinine level of 1.69 to 4.52 mg/dL (149 to 400 μmol/L) who underwent elective coronary angiography or intervention. The indication for angiography was determined by individual cardiologists. All patients had 2 serum creatinine measurements within 1 month before coronary angiography, with intraindividual fluctuation less than 15% to confirm stable renal function before recruitment. Patients with a known allergy to NAC or contrast agents were

Results

There were 46 patients enrolled in the NAC group, and 45 patients, in the control group. Baseline clinical characteristics are listed in Table 1. The NAC group had marginally more patients who had hypertensive nephrosclerosis, were administered aspirin, had renal artery stenosis, had a greater dose of contrast administered, and had a greater estimated GFR at baseline and fewer patients who were administered angiotensin receptor antagonist than the control group, although none of the

Discussion

In this randomized study, there was no difference in incidence of CN between NAC with hydration and hydration alone in patients with moderate to severe renal insufficiency undergoing coronary angiography or interventions. Moreover, there also was no difference in changes in serum creatinine levels or estimated GFRs between the 2 arms. In logistic regression analysis, none of the potential variables, including treatment strategy, predicted the primary end point. Although it has been suggested

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Acute kidney injury (AKI) following exposure to iodinated radiocontrast media used for multiple medical imaging procedures including contrast-enhanced computed tomography and coronary and noncoronary angiography represents one of the most common forms of iatrogenic AKI. Multiple mechanisms are believed to contribute to the nephrotoxicity of these agents, including intrarenal vasoconstriction, hyperosmolality, generation of reactive oxygen species, and direct cytotoxicity. The most important risk factor for development of contrast-associated AKI following contrast exposure is preexisting kidney dysfunction. Other patient-related risk factors include concomitant diabetes mellitus, congestive heart failure, volume depletion, and concomitant administration of other nephrotoxic agents, particularly nonsteroidal anti-inflammatory drugs. The toxicity of iodinated contrast media is related to their osmolality, with higher nephrotoxicity associated with higher osmolal contrast media as compared with low-osmolal contrast media and iso-osmolal contrast media. Other risk factors include the volume of contrast media infused, intra-arterial as compared with intravenous administration, and repeated exposure to contrast media over a short period of time. The primary strategy to mitigate the risk of contrast-associated AKI is periprocedural administration of isotonic crystalloid solutions, although the optimal rate of fluid administration is not known. It is also uncertain whether the use of isotonic sodium bicarbonate provides greater renal protection than isotonic saline. Although periprocedural administration of multiple pharmacological agents, including N-acetylcysteine, adenosine antagonists, statins, and ascorbic acid, have been proposed for prevention of contrast-associated AKI, the true effectiveness of these agents remains uncertain. Other pharmacological agents, including loop diuretics, mannitol, and dopamine, and other dopaminergic agonists, as well as prophylactic hemodialysis and hemofiltration, are not effective at reducing the risk of contrast-associated AKI.
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There have been a myriad of studies investigating the effectiveness of N-acetylcysteine (NAC) in the prevention of contrast induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) with or without percutaneous coronary intervention (PCI). However the consensus is still out about the effectiveness of NAC pre-treatment due to vastly mixed results amongst the literature.
The aim of this study was to conduct a meta-analysis and trial sequential analysis to determine the effects of pre-operative NAC in lowering the incidence of CIN in patients undergoing CAG and/or PCI.
A systematic literature search was performed to include all randomized controlled trials (RCTs) comparing NAC versus control as pretreatment for CAG and/or PCI. A traditional meta-analysis and several subgroup analyses were conducted using traditional meta-analysis with relative risk (RR), trial sequential analysis, and meta-regression analysis.
43 RCTs met our inclusion criteria giving a total of 3277 patients in both control and treatment arms. There was a significant reduction in the risk of CIN in the NAC treated group compared to control (OR 0.666; 95% CI, 0.532–0.834; I2 = 40.11%; p = 0.004). Trial sequential analysis, using a relative risk reduction threshold of 15%, indicates that the evidence is firm.
The results of the present paper support the use of NAC in the prevention of CIN in patients undergoing CAG ± PCI. Future studies should focus on the benefits of NAC amongst subgroups of high-risk patients.
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Contrast induced nephropathy (CIN) is traditionally associated with outpatient imaging studies. More recently, patients afflicted with vascular pathologies are increasingly undergoing endovascular treatments that require the use of iodinated contrast media (CM) agents, thus placing them as risk of developing CIN. As perioperative physicians, anaesthetists should be aware of the risk factors and measures that might minimize acute kidney injury caused by CM. This review evaluates recent data regarding preventive measures against CIN and where possible, places the evidence in the context of the patient receiving endovascular surgical treatment. Measures including the use of peri-procedural hydration, N-acetylcysteine, statins, remote ischaemic preconditioning, renal vasodilators and renal replacement therapy and the use of alternatives to iodinated contrast agents are discussed. It should be noted that most of the available data regarding CIN are from non-surgical patients.
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Acute kidney injury (AKI) is a common condition with multiple etiologies and variable clinical findings and pathologic manifestations. AKI is associated with serious adverse clinical outcomes, including the development of de novo chronic kidney disease, accelerated progression of pre-existing chronic kidney disease, end-stage kidney disease, and increased mortality. Past research has advanced our understanding of the pathophysiology, epidemiology, and outcomes of AKI significantly, however, little progress has been made in the development of evidence-based interventions for its prevention and treatment. In this review, we discuss key considerations in the design of clinical trials in AKI and highlight significant methodologic limitations that precluded many past studies from determining the effectiveness of preventive and therapeutic strategies for this common and serious condition.
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Contrast media induced nephropathy (CIN) is a sudden compromise of renal function 24–48 h after administering contrast medium during a CT scan or angiography. CIN accounts for 10% of hospital acquired renal failure and is ranked the third cause of acquiring this condition. Identifying patients at risk through proper screening can reduce the occurrence of this condition.
This review paper aims to critique current evidence, provide a better understanding of CIN, inform nursing practice and make recommendations for bedside nurses and future research.
An integrative review of the literature was made using the key terms: “contrast media”, “nephritis”, “nephropathy”, “contrast media induced nephropathy scores”, “acute kidney failure”, “acute renal failure” and “acute kidney injury”. MeSH key terms used in some databases were: “prevention and control”, “acute kidney failure” and “treatment”. Databases searched included Medline, CINAHL and Academic Search Complete, and references of relevant articles were also assessed. The search included all articles between the years 2000 and 2013.
Sixty-seven articles were obtained as a result of the search, including RCTs, systematic reviews, and retrospective studies.
Contrast media induced nephropathy is an iatrogenic complication occurring secondary to diagnostic or therapeutic procedures. At times it is unavoidable but a systematic method of risk assessment should be adopted to identify high risk patients for tailored and targeted approaches to management interventions.
As the use of contrast media is increasing for diagnostic purposes, it is important that nurses be aware of the risk factors for CIN, identify and monitor high risk patients to prevent deterioration in renal function when possible.
Pharmacologic Prophylaxis for Contrast-Induced Acute Kidney Injury
2014, Interventional Cardiology Clinics

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Original investigation: pathogenesis and treatment of kidney disease and hypertensionEffect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial

Abstract

Section snippets

Methods

Results

Discussion

Am J Med

Kidney Int

Int J Cardiol

Am J Kidney Dis

Kidney Int

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Kidney Int

J Am Coll Cardiol

Lancet

Kidney Int

Am J Med

J Am Coll Cardiol

Prevention of nephrotoxicity induced by radiocontrast agents

N Engl J Med

Prognostic stratification in critically ill patients with acute renal failure requiring dialysis

Arch Intern Med

Acute renal failure requiring dialysis after percutaneous coronary interventions

Catheter Cardiovasc Interv

Contrast nephropathy

J Am Soc Nephrol

Effect of dopamine on renal function after arteriography in patients with preexisting renal insufficiency

Am Surg

Prediction and prevention of contrast nephropathy

J Interv Cardiol

Effects of saline, mannitol, and furosemide on acute decreases in renal function induced by radiocontrast agents

N Engl J Med

Hypoxia of the renal medulla—Its implications for disease

N Engl J Med

Contrast associated nephropathyPresentation, pathophysiology and management

Miner Electrolyte Metab

Radiocontrast medium-induced declines in renal functionA role for oxygen radicals

Am J Physiol

Original investigation: pathogenesis and treatment of kidney disease and hypertension
Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial