SAN FRANCISCO, June 26 -- Seemingly minor and reversible contrast-induced nephropathy can increase long-term risk of stroke, end-stage renal failure, and other adverse events, researchers found.
The composite rate of these events ranged from 42% to 46% in patients who developed contrast-induced nephropathy compared with 26% to 29% in those who did not (P=0.01 to 0.04), depending on definition, results from a randomized clinical trial reported online in the Clinical Journal of the American Society Nephrology showed.
Action Points
- Explain to interested patients that contrast agents contain substances such as iodine and barium that improve visualization of blood vessels and changes in tissues for medical imaging procedures.
- Note that this randomized clinical trial analysis supported a causal relationship between contrast-induced nephropathy and long-term adverse events that prior studies have not been able to draw.
The findings came from a trial comparing the incidence of nephropathy induced by two contrast agents, iodixanol (Visipaque) and iopamidol (Isovue), said Richard J. Solomon, MD, of the University of Vermont in Burlington, and colleagues.
The higher incidence of nephropathy induced by iodixanol was associated with a significant two- to four-fold higher risk for adverse events one year or more later, they said, providing evidence that the acute kidney injury that can occur with use of contrast agents has serious consequences.
The link with long-term adverse event risk has been controversial, in part, because evidence was primarily from retrospective analyses of large databases or observation of patients after coronary angiography or percutaneous coronary intervention.
This kind of data cannot determine cause-and-effect, the researchers noted, so it was possible that the relationship reflected only confounding if patients with more baseline cardiovascular risk factors were more likely to develop nephropathy from contrast injection.
To determine better evidence of causality, the researchers obtained long-term follow-up of at least one year for 294 patients in the Cardiac Angiography in Renally Impaired Patients (CARE) Study.
The prospective, double-blind clinical trial compared incidence of contrast-induced nephropathy in patients who had moderate to severe chronic kidney disease and were undergoing cardiac angiography randomized to use the low-osmolar, nonionic monomer iopamidol or the iso-osmolar, nonionic dimmer iodixanol as the contrast medium.
Neither of these contrast media is known to affect risk factors that might contribute to long-term adverse events.
The trial used an older definition of contrast-induced nephropathy -- a serum creatinine increase of at least 0.5 mg/dl or 25% -- which did not show a significant difference in incidence between groups (9.8% with iopamidol versus 12.4% with iodixanol, P=0.39).
Another measure suggested to be more sensitive for acute kidney injury -- cystatin C increases of at least 25% -- did show a significant difference between the two treatment arms.
For these definitions as well as a newer one suggested by the Acute Kidney Injury Network -- a serum creatinine increase of at least 0.3 mg/dl -- the incidence of adverse events was statistically higher in patients who developed contrast-induced nephropathy than in patients who did not.
Prospectively defined adverse events included death, stroke, myocardial infarction, end-stage kidney disease, percutaneous coronary revascularization, CABG, other revascularization procedures, and "other." Death, stroke, myocardial infarction, and ESRD that required dialysis were considered major events.
After adjustment for contrast agent used and other baseline risk factors, the incidence rate ratio for all events and major events remained higher in association with contrast-induced nephropathy.
While there were fewer major events and thus lower statistical power for them, contrast-induced nephropathy raised their risk by a similar magnitude as overall adverse events.
The effect on major adverse events was significant for the 3.0-mg/dl-serum creatinine definition of contrast-induced nephropathy (IRR 3.2, P=0.0213).
Whereas neither contrast agent was associated with increased risk of long-term adverse events when contrast-induced nephropathy did not occur, the rate was significantly elevated when it did occur by most definitions among patients given iodixanol versus iopamidol (IRR 2.1 to 2.9, P=0.0177 to P=0.1096).
"Thus, the interaction is largely explained by the higher number of adverse events in patients who had contrast-induced nephropathy after randomization to a less effective treatment for contrast-induced nephropathy," the researchers concluded.
Although the results support a causal relationship between contrast-induced nephropathy and subsequent long-term adverse events, Dr. Solomon's group noted that they could not determine a dose-response relationship that would provide further proof.
The mechanism for the link between contrast-induced nephropathy and long-term adverse events remains unclear, they noted.
| The analysis and the CARE trial were supported by Bracco Diagnostics, which manufactures iopamidol.
Dr. Solomon reported serving as a consultant for Bracco Diagnostics. Co-authors also reported receiving research funding from Bracco Diagnostics. |
Primary Source
Clinical Journal of the American Society Nephrology
Solomon RJ, et al "Contrast-induced nephropathy and long-term adverse events: cause and effect?" Clin J Am Soc Nephrol 2009; DOI: 10.2215/CJN.00550109.