Nephropathy caused by the use of contrast media is a well-known complication of diagnostic angiography and PCI. The use of contrast media can lead to a reversible decline of excretory renal function and is associated with increased in-hospital morbidity, mortality, and costs and longer admissions, especially in patients requiring dialysis, write the investigators.

While the exact pathophysiology of contrast nephropathy is not fully understood, the dye is believed to negatively affect the kidney by altering renal hemodynamics and to increase the production of oxygen free radicals. Prophylactic administration of acetylcysteinea thiol-containing antioxidantcould prevent this damage.

One previous studyas reported by heartwirefound that acetylcysteine improved renal function after administration of radiographic contrast dye in patients undergoing computed tomography (CT).2 Another studyalso reported by heartwirefound acetylcysteine reduced contrast nephropathy in patients undergoing coronary angiography.3

In this meta-analysis, the investigators analyzed seven randomized controlled trials comparing acetylcysteine and hydration with hydration alone for preventing contrast nephropathy in patients with chronic renal insufficiency. The incidence of contrast nephropathydefined by an increase in serum creatinine clearance of at least 0.5 mg/dL or an increase of 25% from baseline values48 hours after the administration of contrast dye served as the primary end point.

In total, the seven trials included more than 805 patients eligible for inclusion in the analysis. Six of the seven studies included patients scheduled for CV interventions requiring intra-arterial administration of contrast dye. The remaining trial investigated intravenous administration of acetylcysteine for elective CT examinations. The mean amount of nonionic contrast dye given ranged from 75 mL to 187 mL.

The overall incidence of contrast nephropathy varied between 8% and 28%. Four of the seven studies included in the meta-analysis showed a significant reduction in the relative risk for development of contrast nephropathy in patients given acetylcysteine, whereas the remaining three studies showed no significant benefit.

When the effect sizes of the seven studies were combined by a random-effects model, the investigators found a 56% reduction in relative risk (relative risk 0.435, 95% CI 0.215-0.879; p=0.02) in patients receiving acetylcysteine. There was no significant relation between the risk of contrast nephropathy and the volume of acetylcysteine administered or the degree of chronic renal insufficiency before the procedure. The results were unchanged through a series of sensitivity analyses.

Our meta-analysis showed a significant benefit of acetylcysteine treatment in prevention if contrast nephropathy in patients with chronic renal insufficiency.

"Our meta-analysis showed a significant benefit of acetylcysteine treatment in prevention of contrast nephropathy in patients with chronic renal insufficiency," write Birck and colleagues. "Whether the observed reduction in relative risk of an arbitrarily defined increase in serum creatinine will confer benefit in clinical practice remains controversial."

The investigators conclude that further trials designed to investigate the course of serum creatinine after radiocontrast media application and to elucidate the effect of acetylcysteine on hard clinical end points are needed.

However, the reported association of contrast nephropathy with increased morbidity, mortality, and hospital stays "might justify use of acetylcysteine for prophylaxis of contrast nephropathy, since it is cheap, easy to use, and has a favorable side-effect profile," they add.

In an editorial accompanying the published study, Dr John A Kellum (University of Pittsburgh Medical Center, PA) writes that despite considerable efforts to develop techniques to prevent acute renal failure, preventing such development in at-risk populations is difficult.4 Several studies have failed to show that several drugs, including low-dose dopamine, atrial natriuretic peptide, or diuretics, can prevent the onset of renal failure ordeterioration of renal function in critically ill patients.

At last we seem to have a drug to prevent, or at least reduce, the occurrence of one common form of acute renal failure.

Kellum adds that acute renal failure remains a poorly defined entity with more than 30 different published biochemical definitions and widely different outcomes, depending on the definitions used. Still, he writes the definition employed by Birck and colleagues0.5 mg/dL rise in serum creatinine at 48 hours following the administration of contrast mediais consistent with international consensus guidelines and definitions.

With patients with diabetes and those with underlying CV or hepatic disease known to be at increased risk of contrast-induced acute renal failure, as well as other patients with sepsis and those receiving nephrotoxic medications, the results of the meta-analysis are encouraging, writes Kellum.

"Given the low costs and good side-effect profile of acetylcysteine, it would seem prudent to give this drug with intravenous fluids to all patients with these risk factors who are receiving intravenous radiographic contrast media," he concludes. "At last we seem to have a drug to prevent, or at least reduce, the occurrence of one common form of acute renal failure."