clinical practice T h e new england journal o f medicine n engl j med 354 4 www.nejm.org january 26, 2006 379 Preventing Nephropathy Induced by Contrast Medium Brendan J. Barrett, M.B., and Patrick S. Parfrey, M.D. From the Division of Nephrology, Memo- rial University of Newfoundland, St. John���s, Newf., Canada. Address reprint requests to Dr. Barrett at the Patient Research Centre, Health Sciences Centre, 300 Prince Philip Dr., St. John���s, NL A1B 3V6, Canada, or at bbarrett@mun.ca. N Engl J Med 2006 354:379-86. Copyright �� 2006 Massachusetts Medical Society. A 71-year-old man with type 2 diabetes and hypertension is referred for coronary an- giography. His medications include metformin and a thiazide. Before the angiogram, his serum creatinine level is 1.8 mg per deciliter (160 ��mol per liter), yielding an esti- mated glomerular filtration rate of 40 ml per minute per 1.73 m2 of body-surface area. What can be done to reduce the risk that an angiographic contrast medium will worsen his kidney function? The Clinical Problem Sensitive tests of kidney function identify mild, transient changes in most patients who have been exposed to intravascular iodinated contrast mediums.1 Clinically important injury (often called contrast-medium���induced nephropathy) is much less common. Cases of contrast-medium���induced nephropathy are usually defined by a fixed (0.5 mg per deciliter [44 ��mol per liter]) or proportionate (25 percent) rise in serum creatinine levels after exposure to the contrast medium. However, the clini- cal importance of such changes, if they are transient, is uncertain. A serum creati- nine level itself is a relatively poor measure of kidney function and is influenced by age, sex, and body composition. In a study by Nash et al.,2 contrast-medium���induced nephropathy was reported to be the third most common cause of acute renal failure in hospitalized patients. In this study, the contrast medium was assumed to be the cause of the renal fail- ure if it was administered in the 24 hours before renal failure and no other major kidney insult was identified. However, exposure to contrast medium may be a con- tributory rather than a sole cause of acute renal failure concomitant insults may include low blood volume, surgery, atheroembolic disease, and the presence of other nephrotoxins. The reported incidence of contrast-medium���induced nephropathy varies among studies, due to differences in definition, background risk, type and dose of con- trast medium, imaging procedure, and the frequency of other potential causes of acute renal failure. The status of renal function before administration of a contrast medium is a major determinant of deterioration in function after administration.3 In one study, serum creatinine levels rose by more than 25 percent in 14.5 percent of patients who underwent coronary angiography (95 percent confidence interval, 12.9 to 16.1 percent).3 In the absence of preexisting renal disease, the incidence is much lower. In a large clinical trial, only 8 percent of patients whose baseline serum creatinine level was below 1.5 mg per deciliter (135 ��mol per liter) had an increase in the serum creatinine level of more than 0.5 mg per deciliter, and none had an increase This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article end with the authors��� clinical recommendations. Downloaded from www.nejm.org on May 20, 2009 . Copyright �� 2006 Massachusetts Medical Society. All rights reserved.

T h e new england journal o f medicine n engl j med 354 4 www.nejm.org january 26, 2006 380 of more than 1 mg per deciliter (89 ��mol per liter).4 In another study, 0.8 percent of 1826 patients required dialysis after exposure to the contrast medium the baseline estimated creatinine clear- ance rate was below 47 ml per minute per 1.73 m2 of body-surface area in all patients requiring dialysis.3 Serum creatinine levels rose by less than 1 mg per deciliter (89 ��mol per liter) in 29 percent of those requiring dialysis, indicating advanced preexisting kidney disease. Registry data suggest a 0.44 percent incidence of nephrop- athy requiring dialysis after percutaneous coro- nary intervention.5 Risk Factors Diabetes is a risk factor for deterioration in renal function after angiography.3,6,7 Other factors vari- ably associated with increased rates of acute re- nal failure after the administration of contrast medium include age over 75 years, periprocedural volume depletion, heart failure, cirrhosis or ne- phrosis, hypertension, proteinuria, concomitant use of nonsteroidal antiinflammatory drugs, and intraarterial injection. In the setting of acute myocardial infarction or percutaneous coronary intervention, hypotension or use of an aortic bal- loon pump has been associated with a higher rate of acute renal failure after exposure to a con- trast medium.7,8 However, it is uncertain to what extent these factors independently worsen renal function, as opposed to serving as markers for coexisting conditions. High doses of contrast medium also increase the likelihood of renal dys- function. The tolerable dose of contrast medium depends on kidney function.3,5,9 Prognosis Contrast-medium���induced nephropathy is usually transient, with serum creatinine levels peaking at 3 days after administration of the medium and returning to baseline within 10 days after ad- ministration.8,10 Appreciable nephropathy is un- likely to develop if the serum creatinine level does not increase by more than 0.5 mg per deci- liter within 24 hours.11 Few studies report kidney function beyond a few days after exposure to the contrast medium. In one report, 5 of 21 elderly patients with an initial sudden rise in serum cre- atinine levels after angiography had a final cre- atinine level of at least 0.5 mg per deciliter above baseline.12 Thirteen to 50 percent of patients re- quiring dialysis after exposure to a contrast me- dium may depend on dialysis permanently.3,13 A decline in kidney function after the admin- istration of a contrast medium is associated with a prolonged hospital stay, adverse cardiac events, and high mortality both in the hospital and in the long term.3,6,8,14-16 However, the association between these outcomes and the decline in func- tion may be explained at least in part by coexist- ing conditions, acuteness of illness, or other causes of acute kidney failure, such as atheroem- bolism. Pathogenesis The pathogenesis of contrast-medium���induced nephropathy in humans is not clear. In vitro studies and studies in animals suggest a combi- nation of toxic injury to the renal tubules and ischemic injury partly mediated by reactive oxy- gen species.17,18 Low blood flow in the medulla, which has a high demand for oxygen, might re- sult from increased perivascular hydrostatic pres- sure, high viscosity, or changes in vasoactive sub- stances such as endothelin, nitric oxide, and adenosine.10,19 Factors impairing medullary vaso- dilation, such as nonsteroidal antiinflammatory drugs, may worsen contrast-medium���induced ne- phropathy. Strategies and Evidence Evaluation of risk The first steps in reducing the risk of kidney in- jury are to look for risk factors and review the indications for the administration of contrast medium. Most risk factors can be detected by history taking and physical examination. Factors such as dehydration can be at least partially cor- rected before exposure to the contrast medium. The risk of a decline in kidney function after the administration of contrast medium rises ex- ponentially with the number of risk factors pres- ent.8,12,14 Validated risk-prediction models, such as the one shown in Table 1, have been devel- oped for patients undergoing percutaneous cor- onary intervention.7 It is not necessary to measure the serum cre- atinine levels of every patient before exposure to a contrast medium, but measurements should be made before intraarterial use of the medium and in patients with a history of kidney disease, pro- teinuria, kidney surgery, diabetes, hypertension, Downloaded from www.nejm.org on May 20, 2009 . Copyright �� 2006 Massachusetts Medical Society. All rights reserved.