Acetylcysteine for prevention of contrast nephropathy: meta-analysis

doi:10.1016/S0140-6736(03)14189-X

The Lancet

Volume 362, Issue 9384, 23 August 2003, Pages 598-603

https://doi.org/10.1016/S0140-6736(03)14189-X Get rights and content

Summary

Background

Contrast nephropathy is associated with increased in-hospital morbidity and mortality and leads to extension of hospital stay in patients with chronic renal insufficiency. Acetylcysteine seems to be a safe and inexpensive way to reduce contrast nephropathy. We aimed to assess the efficacy of acetylcysteine to prevent contrast nephropathy after administration of radiocontrast media in patients with chronic renal insufficiency.

Methods

We did a meta-analysis of randomised controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The trials were identified through a combined search of the BIOSIS+/RRM, MEDLINE, Web of Science, Current Contents Medizin, and The Cochrane Library Databases. We used incidence of contrast nephropathy 48 h after administration of radiocontrast media as an outcome measure.

Findings

Seven trials including 805 patients were eligible according to our inclusion criteria and were analysed. Overall incidence of contrast nephropathy varied between 8% and 28%. Since significant heterogeneity was indicated by the Q statistics (p=0·016) we used a random-effects model to combine the data. Compared with periprocedural hydration alone, administration of acetylcysteine and hydration significantly reduced the relative risk of contrast nephropathy by 56% (0·435 [95% CI 0·215–0·879], p=0·02) in patients with chronic renal insufficiency. Meta-regression revealed no significant relation between the relative risk of contrast nephropathy and the volume of radiocontrast media administered or the degree of chronic renal insufficiency before the procedure.

Interpretation

Compared with periprocedural hydration alone, acetylcysteine with hydration significantly reduces the risk of contrast nephropathy in patients with chronic renal insufficiency. The relative risk of contrast nephropathy was not related to the amount of radiocontrast media given or to the degree of chronic renal insufficiency before the procedure.

Introduction

Radiocontrast media can lead to a reversible decline of excretory renal function that starts soon after administration, with an incidence of 10–30% in selected high-risk patients. Generally, this form of acute renal failure follows a benign course and only rarely necessitates use of dialysis.1, 2, 3 Nevertheless, use of radiocontrast media has been associated with increased in-hospital morbidity, mortality, and costs of medical care, and long admissions, especially in patients needing dialysis.4, 5, 6, 7

Unfortunately, the best treatment to prevent contrast nephropathy remains to be established.¹ Trials of diuretics, dopamine, calcium-channel blockers, atrial natriuretic peptides, aminophylline, and endothelin antagonists have yielded contrasting results.¹ Only periprocedural hydration is widely accepted to prevent contrast nephropathy.1, 8, 9

Radiocontrast media reduces renal excretory function by altering renal haemodynamics and by exerting direct tubulotoxic effects.¹ Although the exact pathophysiology of contrast nephropathy is not understood fully, results of work in animals have implicated reactive oxygen species in the pathogenesis of this disorder.10, 11

Prevention of contrast nephropathy might be possible with the antioxidative agent acetylcysteine.12, 13 In a randomised controlled trial¹⁴ in patients with chronic renal insufficiency, acetylcysteine significantly reduced incidence of contrast nephropathy after intravenous administration of radiocontrast media for elective CT examinations. However, results have contrasted in six other randomised controlled trials15, 16, 17, 18, 19, 20 in which the effectiveness of acetylcysteine was assessed in patients with chronic renal insufficiency. We aimed to assess whether prophylactic use of acetylcysteine reduces incidence of contrast nephropathy in patients with renal insufficiency.

Section snippets

Methods

We did this meta-analysis according to a predetermined protocol following the recommendations of the quality of reporting of meta-analysis (QUOROM) statement.²¹ To identify relevant studies, we searched BIOSIS+/RRM (1989 onwards), MEDLINE (1966 onwards), Web of Science (1997 onwards), the Current Contents Medizin (current contents of medical journals publishing in German language), and The Cochrane Library (1996 onwards). For the first four databases we used the keywords contrast nephropathy,

Statistical analysis

For every trial we calculated the relative risk for the primary outcome. The Q statistic was calculated to assess if significant heterogeneity was present between the included trials. This statistic tests the null hypothesis that the underlying effect measured by the pooled studies is equivalent. For p values less than 0·1 this assumption was deemed invalid.²³ Since the Q statistic indicated that significant heterogeneity was present, we used the random-effects model to combine the effect sizes

Results

We identified 13 references describing studies in which acetylcysteine was used for prevention of contrast nephropathy in patients with chronic renal insufficiency, all of which were published between 2000 and 2003. Eight were full-length reports in peer-reviewed journals,14, 15, 16, 17, 18, 19, 20, 31 one was non-English,³¹ and five were abstracts.32, 33, 34, 35, 36 Some of these studies used a quasi-randomised design per se³⁴ or with respect to chronic renal insufficiency,³¹ used either

Discussion

Contrast nephropathy is the third leading cause of acute renal failure in patients who had been admitted, accounting for 10% of all cases.³⁷ Generally, it follows a benign course, and persistent renal impairment and dialysis dependency are rare.⁴ In selected subgroups of patients, however, like those with pre-existing renal insufficiency or diabetes mellitus, up to 7% require transient dialysis or progress to end-stage renal disease.⁵ The occurrence of contrast nephropathy has also been

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ArticlesAcetylcysteine for prevention of contrast nephropathy: meta-analysis

Summary

Background

Methods

Findings

Interpretation

Introduction

Section snippets

Methods

Statistical analysis

Results

Discussion

Am J Med

J Am Coll Cardiol

Kidney Int

Kidney Int

J Am Coll Cardiol

J Am Coll Cardiol

Am J Cardiol

Control Clin Trials

Control Clin Trials

Lancet

Am J Med

Contrast nephropathy

J Am Soc Nephrol

Contrast material-induced renal failure in patients with diabetes mellitus, renal insufficiency, or both. A prospective controlled study

N Engl J Med

Incidence, risk factors, and clinical course of acute renal insufficiency after cardiac catheterization in patients 70 years of age or older: a prospective study

Arch Intern Med

The effect of acute renal failure on mortality: a cohort analysis

JAMA

Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention

Circulation

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

N Engl J Med

A randomised prospective trial to assess the role of saline hydration on the development of contrast nephropathy

Nephron Clin Pract

Radiocontrast medium-induced declines in renal function: a role for oxygen radicals

Am J Physiol

Acetylcysteine and contrast media nephropathy

Curr Opin Nephrol Hypertens

Articles
Acetylcysteine for prevention of contrast nephropathy: meta-analysis