Preventing Contrast Nephropathy

Abstract & Commentary

Synopsis: Meta-analysis of published clinical trials showed that a regimen of oral acetylcysteine administration along with hydration reduced the relative risk of developing contrast nephropathy by 56% among patients with pre-existing renal insufficiency.

Source: Birck R, et al. Acetylcysteine for prevention of contrast nephropathy: Meta-analysis. Lancet. 2003;362:598-603.

Radiocontrast media can lead to a reversible deterioration in renal function beginning soon after administration in 10-30% of patients with underlying renal insufficiency. A number of clinical trials have evaluated the efficacy of acetylcysteine (Mucomystâ) administration, along with periprocedural hydration, in preventing or reducing the severity of this complication. Because the results of these studies have been inconsistent, Birck and associates at the University of Mannheim performed a rigorous meta-analysis of published data to examine the overall effect of this agent.

Birck et al followed the guidelines of the QUORUM Group1 in performing and reporting the results of their meta-analysis. They identified 13 studies published between 2000 and 2003 that examined the effect of acetylcysteine in preventing contrast-induced nephropathy. The most common dose of acetylcysteine given was 600 mg twice daily orally for 4 doses; however, a few trials gave more or less of the drug or administered it intravenously. The primary outcome measure was development of contrast nephropathy defined as an increase in serum creatinine of at least 0.5 mg/dL or an increase of 25% from baseline in the 48 hours following administration of contrast media.

Seven trials fulfilled all of Birck et al’s predetermined criteria, reporting results from 805 patients with underlying renal insufficiency who were given 75-187 mL of intravenous contrast material. The overall incidence of contrast nephropathy in these trials was 8-28%; 4 of the 7 studies showed a significant benefit from acetylcysteine, and 3 showed no difference from hydration alone. According to the meta-analysis, the administration of acetylcysteine and hydration reduced the relative risk of developing contrast nephropathy in patients with underlying renal insufficiency by 56% (0.435; 95% confidence interval, 0.215-0.879; P = 0.02). There was no significant relationship between the relative risk of contrast nephropathy and the volume of radiocontrast material infused, or with the degree of pre-existing renal insufficiency.

Comment by David J. Pierson, MD

Publication of the positive results of the first randomized, controlled, clinical trial of acetylcysteine administration to prevent contrast nephropathy2 created quite a stir among clinicians and the medical media. Several subsequently published studies had less impressive results, and it remained unclear just how effective this therapy was. This meta-analysis, performed rigorously and according to what are currently felt to be the appropriate standards, shows that the effect appears to be real and substantial.

Although acute renal failure is an independent risk factor for mortality in hospitalized patients, contrast nephropathy is a poorly defined condition in critically ill patients. In an editorial accompanying the Birck paper,3 Kellum points out that the clinical relevance of preventing a 0.5 mg/dL increase in serum creatinine in about half of high-risk patients receiving contrast media through the administration of acetylcysteine is uncertain in many cases. Nonetheless, acetylcysteine is a relatively safe and inexpensive drug, and its use along with appropriate hydration should be strongly considered whenever radiocontrast material is to be administered to high-risk patients. According to Kellum, patients who would potentially benefit from administration of acetylcysteine in combination with hydration include those with diabetes, cardiac, or liver disease, as well as those with pre-existing chronic renal insufficiency.

Dr. Pierson is Professor of Medicine University of Washington Medical Director Respiratory Care Harborview Medical Center, Seattle.

References

1. Moher D, et al, for the QUORUM Group. Improving the quality of reports of meta-analysis of randomized controlled trials. Lancet. 1999;354:1896-1900.

2. Tepel M, et al. Prevention of radiographic-contrast-induced reductions in renal function by acetylcysteine. N Engl J Med. 2000;343:180-184.

3. Kellum JA. A drug to prevent renal failure? Lancet. 2003;362:589-590.