Radiocontrast-Induced Nephropathy

Contrast-induced nephropathy (CIN) is a well-recognized complication of angiographic procedures. The incidence varies according to the population studied, the definition applied and the vigilance of the angiographer in measuring post procedure renal function. As more cardiovascular contrast studies are performed each year, it is timely for the Journal to raise the awareness of this entity through a comprehensive review of the subject1 and to reopen the issue of prevention by publishing a study showing the potential protective benefit of N-acetylcysteine.2 The articles appearing in this month’s issue raises several important clinical questions. What is CIN? Although there are several definitions, CIN is generally defined as a > 25% rise in creatinine from baseline or an absolute rise > 0.5 mg/dl for which alternative explanations for renal impairment have been excluded.3 The incidence in patients with and without diabetes is approximately 20% and 13%, respectively. Although there are several tests available to make the diagnosis, measurement of serum creatinine is the clinical gold standard to make the diagnosis and follow its natural history. What are the consequences of CIN? In the general population of patients, the natural history of CIN is a transient rise in serum creatinine following contrast agent administration that peaks at 48–72 hours with return to baseline by 7 days. The clinical manifestations of CIN can range from just a rise in creatinine to oliguria (less than 25% of the time) or anuria. The need for dialysis is rare (0.5–2.0%) and prolongation of hospitalization and its economic consequences have been documented.4 Who are the high-risk patients for CIN? The two major risks for CIN are the presence of baseline renal insufficiency and diabetes mellitus. Minor increased risk is associated with heart failure, dehydration, hypotension, hypoxia and older age. Clearly, the risks are additive. What strategies afford protection for CIN? The only proven method to prevent or reduce CIN is hydration with saline. The type (nonionic) and total volume (less than 50 ml) of contrast are directly related to incidence. Aminophylline, theophylline, low-dose dopamine, forced diuresis, prostaglandin E1, calcium channel antagonists, ACE-inhibitors, fenoldopam and post-procedure hemodialysis have been studied with inconsistent results and no clear benefit. In the paper by Tadros et al., fifty-five patients with baseline creatinine > 1.2 mg/dl received intravenous hydration before and after the procedure, and 600 mg of N-acetylcysteine orally twice on the day before and twice on the day of catheterization (one dose pre- and post-arteriography). The mean change in creatinine after 48 hours was -0.4 ± 0.3 for the treated group compared to +0.1 ± 0.3 mg/dl (p = 0.04). A larger benefit was seen in patients with baseline creatinine > 2.0 mg/dl. Although the authors present concordant studies from the literature in their discussion, it should be noted that there are studies that do not report an overall benefit to N-acetylcysteine.5 What should be the clinical approach to arteriography to prevent CIN? • In low-risk patients (no baseline renal impairment, no diabetes, no heart failure), no adjunctive prevention therapy is necessary and the use of non-ionic contrast material offers no value for the increased cost. • Since the breakpoint between cardiovascular risk corresponds to a serum creatinine of 1.5 mg/dl [especially with coincident microalbuminuria (> 30 mg/l on a single voided specimen)] or in any patient with diabetes, the minimal strategy should include pre- and post-procedure hydration with saline. From a cost-effective standpoint, the literature supports outpatient oral hydration before the procedure with intravenous hyperhydration for six hours following the procedure. In the absence of oliguria or heart failure it is reasonable not to prolong hospitalization and check the creatinine 5–7 days after the procedure to document a return to baseline levels. For all of these patients, non-ionic contrast in the smallest volume necessary for diagnostic images should be employed. This may include substituting an echocardiogram to determine valvular and LV function rather than using the volume of dye required for left ventriculography. Avoidance of non-steroidal anti-inflammatory drugs is an important but often overlooked additional maneuver for anyone at risk. • For patients with creatinine levels more than 2.0 mg/dl, it is reasonable to add N-acetylcysteine to the regimen pre- and post-procedure according to the protocol described in the Tadros paper. • For patients on the verge of dialysis (creatinine > 4), every effort to avoid dye must be made (exhaust all non-catheterization testing and maximize medical treatment) since dye loads of any size often push these patients over the edge and hasten the need for dialysis. It is logically better for these patients to have a working dialysis access prior to catheterization and a planned post procedure hemodialysis may have prophylactic benefit when selectively employed in this population. Future directions. It is probable that advances in CT and or MRI will be able to provide adequate visualization of the coronary anatomy (especially as new isotope based imaging agents are developed) and offered as an alternative to patients with high risk of CIN. A study was recently reported where gadolinium (no known renal toxicity) was mixed with non-ionic contrast in a 2:1 ratio. Fifteen patients with impaired renal function underwent coronary arteriography. The total amount of non-ionic dye was limited to a mean of 44 ml. The studies were all diagnostic and the risk of CIN was dramatically reduced. The trade-off was the not inconsequential cost of the gadolinium that was much greater than non-ionic contrast alone.6 Finally, as we examine the relationship between contrast dye and coronary arteriography, it is important to reemphasize the intersection of nephrology and cardiology in general. In addition to the increased risk of restenosis and myocardial infarction, patients with renal disease are predisposed to many of the treatable risk factors for atherosclerosis and may represent a missed opportunity if we don’t strive to provide aggressive secondary prevention when they leave the catheterization lab.

1. Gomes VO, et al. Contrast-medium induced nephropathy in patients undergoing coronary angiography. J Invas Cardiol 2003;15:304–310. 2. Tadros GM, et al. Prevention of radiocontrast-induced nephropathy with N-acetylcysteine in patients undergoing coronary angiography. J Invas Cardiol 2003;15:311–314. 3. Porter GA. Contrast-associated nephropathy. Am J Cardiol 1989;64:22E–26E. 4. McCullough PA. Interface between heart disease and renal dysfunction: From assessment to action. ACC Current Journal Review 2003;March/April: 20–24. 5. Briguori C, et al. Acetylcysteine and contrast-agent associated nephrotoxicity. J Am Coll Cardiol 2002;40:298–303. 6. Sarkis A, et al. Gadolinium-enhanced coronary angiography in patients with impaired renal function. Am J Cardiol 2003;91:974–975.