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Is Contrast-Induced Acute Kidney Injury a Myth?

Roberts, James R. MD

doi: 10.1097/01.EEM.0000581520.54814.26
InFocus

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When iodinated contrast was first introduced, many patients with pre-existing kidney disease experienced acute injury, but the evolution of safer agents has resulted in a much lower incidence of acute kidney injury.

The risk of this injury due to contrast, in fact, may be overstated. Even its existence has been questioned.

Today, contrast is not required as often as it was in the past because of high-resolution CT scanners, but it is often recommended by radiologists for many studies.

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Contrast-Associated Kidney Injury

Mehran R, Dangas GD, Weisbord SD

N Engl J Med.

2019;380(22):2146

This review summarizes the known pathophysiology of contrast-associated kidney injury, the diagnostic criteria, and risk stratification, and it discusses the controversies about the actual incidence of this condition. It also investigates interventions that have been studied to prevent contrast-associated kidney injury.

The exact mechanism by which contrast causes kidney injury is somewhat obscure. Direct and indirect effects and hemodynamic perturbations have been implicated. Contrast agents are directly toxic to epithelial cells, and exposure may cause the outright death of these cells. Indirect injury is related to intrarenal vasoactive activities adversely affected by contrast. The adverse hemodynamic effects of contrast, primarily renal vasoconstriction, are particularly problematic for the renal medulla, a portion of the kidney that is susceptible to injury from decreased blood flow.

Declining kidney function after contrast administration, referred to as contrast-induced nephropathy, has been historically defined as an increase in plasma creatinine of at least 0.5 mg/dL or a 25 percent increase from baseline within two to five days. Other criteria define contrast-induced acute kidney injury as an increase in plasma creatinine by a factor of 1.5 x baseline within seven days of exposure. Plasma creatinine levels, although commonly used, have relatively poor sensitivity to kidney dysfunction.

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The strongest independent risk factor for contrast-associated acute kidney injury is preexisting chronic kidney disease. Lower levels of kidney function are associated with higher degrees of risk. Diabetes was once thought to be an independent risk factor, but it is not considered to be associated with kidney injury except for an increased susceptibility in diabetics with underlying chronic kidney disease. Contrast-associated kidney dysfunction has been markedly reduced by the introduction of low-osmolarity contrast agents, and they are now used in all studies. Using a high volume of contrast and repeat administration within 72 hours, however, have been associated with increased risk. Angiography and angioplasty, such as cardiac angioplasty in patients with ST-segment elevation myocardial infarction, are also associated with an increased incidence of deteriorating kidney function from contrast.

There is a lot of uncertainty about the causal relationship between contrast-associated acute kidney injury and adverse clinical outcomes, morbidity, and mortality. Many studies, however, have demonstrated an overall increased mortality associated with contrast-induced acute renal injury and an accelerated progression of underlying chronic kidney disease. The existence of contrast-induced acute kidney dysfunction was questioned in a meta-analysis of 25,950 patients that showed similar risks for acute kidney injury and death in those undergoing procedures with and without iodinated contrast. (Radiology. 2013;267[1]:119; http://bit.ly/2LiSY9P.)

Curiously, another meta-analysis demonstrated a significantly lower risk of acute kidney injury in patients with acute ischemic stroke who underwent CT with and without contrast. (Stroke. 2017;48[7]:1862; http://bit.ly/2XJHygZ.) Importantly, a number of analyses have concluded that using contrast does not appear to be associated with an increased risk of acute kidney injury. These authors questioned the clinical importance of contrast-induced renal dysfunction, and stated that current data are insufficient to declare that contrast agents are not nephrotoxic and that severe acute kidney injury characterized by substantial decrements in kidney function and the need for renal replacement therapy appear to be infrequent after intravascular contrast administration.

Though the question of the existence of contrast-induced kidney injury has not been settled, a number of interventions to prevent it or decrease creatinine elevations have been investigated. Intravascular volume expansion has been touted to have a protective renal effect, but randomized clinical trials are relatively sparse. A number of small studies have demonstrated a markedly lower incidence of contrast-induced acute kidney injury by using saline before administering the dye.

Guidelines from the American College of Radiology and the European Society of Cardiology recommend intravenous isotonic saline for a number of hours before and after administering contrast. The saline volume is relatively small, from 100 mL per hour for six to 12 hours before and 12 hours after angiography to 1.5 mL per kg per hour for 12 hours before and after contrast exposure. The commonly quoted AMACING study did not demonstrate any benefit of preprocedural intravenous saline in preventing acute kidney injury. (Lancet. 2017;389[10076]:1312.) This study had some methodological flaws, however, making it premature to conclude that IV fluids are not effective or unnecessary before administering contrast. Other studies found that adding sodium bicarbonate to normal saline has no benefit in preventing contrast-associated acute kidney injury.

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Pretreatment with acetylcysteine was once believed beneficial, but has shown no value. No data support discontinuing a variety of medications (diuretics, ACE inhibitors, and NSAIDs) before dye administration. Even stopping metformin, a previous standard, has not been supported by evidenced-base studies. It should be noted that metformin is associated with lactic acidosis, not acute renal injury.

These authors conclude that the definition of contrast-induced renal injury and the studies showing an association with serious adverse outcomes are unclear. Despite previous dogma, the current thinking is that additional study is needed to address the controversy over the true toxic effects of contrast and to determine whether there is any justification for limiting its use in patients at elevated risk.

Comment: This subject is confusing and the evidence somewhat contradictory, and concepts have changed significantly over the past few years. Recent data have questioned previous views that acute kidney injury is significant in patients given contrast. Clinical relevance of small increases in creatinine has also been questioned. The viscosity and osmolarity of iodinated contrast do show some renal toxicity, but there has been a marked change in our understanding of any true detrimental effect of contrast in patients undergoing CT scans. Emergency physicians do not order dye for angiographic procedures, which are probably most likely to be associated with contrast-induced nephropathy.

The most effective preventive regimen for patients at high risk appears to be intravenous sodium chloride administration, but even the actual benefit of hydration has not been determined. A prolonged infusion of saline before and after a procedure is not possible in the ED, but it seems reasonable to give generous IV saline before contrast in dehydrated patients. I always give one liter of saline for any dye study—500-600 mL before and 400-500 mL after.

Recent studies have caused clinicians to question whether there is actually a condition such as contrast-induced nephropathy. Contrast is necessary to obtain or assess diagnostic accuracy in some radiographic procedures. Omitting contrast when it is indicated or giving it when it is not can lead to diagnostic and treatment errors. It is generally agreed that patients with a GFR greater than 30 mL/min can be safely administered contrast material.

It should be noted that allergic-like (hypersensitivity) reactions and other physiological reactions to contrast do exist. Importantly, allergic-type reactions are idiosyncratic and don't seem to be related to dose or type of contrast. The risk for immediate hypersensitivity reactions to contrast is increased in patients with allergies or asthma, but there is no relationship between dye reactions and allergy to shellfish or topical iodine solutions. It has long been a misconception that patients can have an iodine allergy and not be given contrast safely. Shellfish allergies are not due to iodine but to muscle protein. Iodine sensitivity does not actually exist.

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Dr. Robertsis a professor of emergency medicine and toxicology at the Drexel University College of Medicine in Philadelphia. Read the Procedural Pause, a blog by Dr. Roberts and his daughter, Martha Roberts, ACNP, PNP, athttp://bit.ly/EMN-ProceduralPause, and read his past columns athttp://bit.ly/EMN-InFocus.

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