Letter to the Editor—Solomon about Laskey Study

“Nephrotoxicity of iodixanol versus iopamidol in patients with chronic kidney disease and diabetes mellitus undergoing coronary angiographic procedures,” Warren Laskey, Peter Aspelin, Charles Davidson, Michael Rudnick, Pierre Aubry, Sreenivas Kumar, Frank Gietzen, Marcus Wiemer, on behalf of the DXV405 Study Group, Am. Heart J. 2009;158:822-28.e3.

The study reported by Laskey et al in the American Heart Journal in November 2009 is an important contribution to the continuing research regarding the safety of contrast media. Their study involved a large number of high risk patients (both chronic kidney disease and diabetes mellitus) exposed to iodinated contrast media. The cohort was not exposed to pharmacologic prophylaxis (N-acetylcysteine or bicarbonate) as in other trials. Furthermore, all cases of acute kidney injury were adjudicated before being considered cases of contrast-induced nephropathy (CIN). The randomization process was effective in distributing equally all potential risk factors for CIN except for the dose of contrast media.

The authors correctly identified the definition of CIN as an important factor in the heterogeneity of results in the literature. They, however, have not taken advantage of this very well designed and administered study. When baseline serum creatinine level is <2.0 mg/dL (average in the trial was 1.7 mg/dL), the use of a definition of CIN that includes a ≥25% increase in serum creatinine level will yield a higher incidence of CIN and thus more statistical power to evaluate differences between treatment arms.1 This definition is associated with both increased short and long-term mortality and is therefore of clinical relevance. Additional definitions of acute kidney injury caused by contrast media, including an absolute increase of ≥0.3 mg/dL in serum creatinine level, have been proposed and also appear to be valid surrogate markers for long-term adverse event rates.2 Because these other definitions are widely used in the literature (≥25% relative increase) and becoming standard within the acute kidney injury literature (≥0.3 mg/dL absolute increase), it would be valuable to have the results of this important trial further supported by reporting these definitions of CIN. Finally, reporting the combination of both ≥25% and ≥0.5 mg/dL captures the maximum number of CIN events in patients with baseline creatinine level above and below 2.0 mg/dL.

Regardless of the incidence of contrast media–induced kidney injury, it is the consequences of that injury that are most relevant to clinicians. Increased short- and long-term mortality after CIN has repeatedly been described. Since this study was completed in February 2007, the study organizers have the opportunity to perform follow-up data collection on these patients and let cardiologists know what happened to these patients. These data, too, inform all users of contrast media about the consequences of their choice of contrast media in high-risk patients.