For some time, clinicians may have been reluctant to order imaging procedures with contrast because of a possible increased risk for acute kidney injury (AKI). But recent research has cast some doubt on the nature of this relationship.
For example, no randomized controlled trial has compared rates of AKI in patients undergoing contrast-enhanced versus noncontrast CT scans, and other factors such as medications, severity of illness, and hypotension can act as confounders, according to Paul M. Palevsky, MD, FACP.
“With this uncertainty, I prefer the term ‘contrast-associated nephropathy’ rather than ‘contrast-induced nephropathy,’” said Dr. Palevsky, who is chief of the renal section at the VA Pittsburgh Healthcare System and professor of medicine and clinical and translational science at the University of Pittsburgh School of Medicine.
In addition, the studies that caused concern about contrast and AKI were experimental, and most focused on coronary angiograms, Dr. Palevsky said. He noted that arteriography is associated with a higher risk of AKI than CT due to the overall risk profile of patients needing such procedures and the more concentrated contrast that's delivered to the kidneys.
Researchers have been working hard in recent years to better understand contrast-associated AKI. “There have been sort of two competing lines of investigation that have collectively underscored why this is an area that continues to be of interest,” explained Steven Weisbord, MD, MSc, a staff nephrologist at the VA Pittsburgh Healthcare System.
“The first one is . . . a series of studies principally in the setting of CT scans, not angiograms, that have suggested that the administration of contrast may not cause acute kidney injury,” said Dr. Weisbord. “And that's counterbalanced by a series of studies, going back now closing in on 20 years, that suggests that procedures in the hospital, particularly angiograms, are being underutilized in patients with kidney disease, because providers are concerned about precipitating acute kidney injury.”
This avoidance of procedures due to perceived risk of contrast-associated AKI is what some nephrologists refer to as “renalism,” said Dr. Palevsky.
Research along the first line includes a 2008 study, published in the Clinical Journal of the American Society of Nephrology, which found that contrast-associated AKI occurred in fewer than 1% of patients who had an estimated glomerular filtration rate (eGFR) greater than 45 mL/min per 1.73 m2 before receiving IV contrast.
A more recent meta-analysis of 13 controlled studies involving 25,950 low-risk patients, published in Radiology in 2013, found that the average rates of AKI were nearly identical between those who received imaging with contrast (6.4%) and those who didn't (6.5%). The incidence rates of dialysis and death were also similar, and the rate of postprocedure dialysis was just 0.3% for the contrast group.
Nephrologists say advances in contrast have helped lower the incidence of contrast-associated AKI. “Twenty-five years ago, it was common to see renal failure after a contrast load due to high osmolar agents that were very hypertonic and the massive doses we used. Now, we only use low-osmolar contrast material in much lower amounts,” said Harold M. Szerlip, MD, FACP, chief and fellowship program director in the division of nephrology at Baylor University Medical Center in Dallas.
In addition, Dr. Palevsky noted, “The volume of contrast given for cardiac catheterization and other angiographic procedures has also decreased over time as imaging techniques improved.”
That doesn't mean that contrast-associated AKI is entirely obsolete, though, experts said. “I think most people, myself included, believe that contrast can cause acute kidney injury,” said Dr. Weisbord. “There are biologically plausible mechanisms and there's a large literature that supports that.”
There are also concerns about the clinical validity of recent evidence. “The knock on these studies is that they're retrospective, and they're subject to certain biases, in that patients who come into the hospital who are sicker, who are more likely to develop AKI, tend to be the ones where providers say, ‘Well, I don't want to administer contrast,’ so there's a bias away from finding the true incidence of acute kidney injury from contrast,” Dr. Weisbord said.
Dr. Palevsky agreed. “This bias is highlighted by the finding, in some studies, of a paradoxically lower risk of AKI in patients who received contrast,” he said.
Another reason for continued concern is that the data are less clear about the safety of contrast-enhanced CT imaging in patients with chronic kidney disease (particularly stages 4 and 5). One study, published in Radiology in 2013, found that patients with a stable eGFR less than 30 mL/min/1.73 m2 had a nearly threefold higher risk of AKI with receipt of contrast compared to those who got noncontrast CT imaging.
On the other hand, a study published in Mayo Clinic Proceedings in 2015 found that rates of AKI, emergency dialysis, or mortality were similar between contrast and noncontrast patients, even those with advanced chronic kidney disease.
Given the uncertainty of the evidence, the experts recommend individualized decision making and preventive strategies for higher-risk patients.
“Underlying impairment in kidney function, chronic kidney disease, is the principal risk factor. Diabetes amplifies the risk in the setting of chronic kidney disease but probably is not an independent risk factor,” said Dr. Weisbord. Other risk factors include intravascular volume depletion and heart failure.
These risk factors should mainly be used to target interventions to prevent AKI, rather than rule out scans, the experts agreed. “The key here is that if a patient has a clear clinical indication for a procedure with contrast, and there is no equivalent alternative procedure that doesn't require contrast, then the procedure should be performed,” said Dr. Weisbord.
Clinicians should talk to patients about the possibility of AKI, Dr. Palevsky suggested. “Engage in shared decision-making with the patient and use appropriate interventions to mitigate risk,” he said.
Of course, it would be helpful to have a cutoff for determining which patients should be treated as high risk, but “that's a matter of fairly significant debate,” said Dr. Weisbord.
“If patients need contrast, I would order it unless they had severe chronic kidney disease or stage 3b [eGFR 30 to 45 mL/min/1.73 m2] with diabetic nephropathy. In those cases, I would evaluate the risks and benefits associated with contrast study,” said Dr. Szerlip.
When to implement preventive strategies may depend on their feasibility. “There are different thresholds for different settings,” said Dr. Weisbord. “If the patient is in the hospital then and it's not an emergent procedure, then you know you can be a bit more liberal and say, ‘Well, OK, anybody under 60 [mL/min/1.73 m2], they get IV fluids, particularly for angiograms.”
If, on the other hand, an outpatient scheduled for a scan would have to be brought in specifically to receive fluids, the cutoff may drop to 30 to 45 mL/min/1.73 m2, he added.
Administering fluids before and after procedures is the most widely used prevention strategy. “There has been controversy in the literature as to whether intravenous bicarbonate is superior to isotonic [normal] saline. In addition, N-acetylcysteine has been proposed as a protective antioxidant for nearly two decades,” said Dr. Palevsky.
The Prevention of Serious Adverse Events Following Angiography (PRESERVE) trial compared these interventions and concluded that 1.26% isotonic sodium bicarbonate was not superior to 0.9% of isotonic saline and that oral N-acetylcysteine was not superior to oral placebo. No significant differences were found in the primary endpoint, which was incidence of death, need for dialysis, or persistent increase in serum creatinine level, defined as at least 50% from baseline, or in the secondary endpoint of contrast-associated AKI.
The trial, which was published by the New England Journal of Medicine on Feb. 15, 2018, was limited because it excluded patients who had emergency procedures and those who received a low overall median volume of contrast material, defined as 85 mL or less, the authors noted.
Given the evidence, however, the experts generally recommend isotonic saline. For hospitalized patients at high risk of contrast-associated AKI, saline should be given at a rate of 1 mL/kg of body weight per hour for up to six to 12 hours, Dr. Palevsky advised.
He added, “If there isn't time to give fluids over an extended period of time preprocedure, then I would give 3 mL/kg over one hour prior to the procedure—it's rare to not get that amount of fluid in.”
Another question has been whether the route of administration (IV or oral) affects the risk of contrast-associated AKI. A Dutch randomized trial, published by The Lancet on Feb. 20, 2017, found no difference in the rate of AKI between the two types of administration. However, the overall population studied was low risk, with an overall rate of contrast-associated AKI of less than 3%.
Dr. Palevsky also advised discontinuing other nephrotoxic medications the patient might be taking, especially NSAIDs.
Angiograms have been a particular target of concern about contrast-associated AKI, and so to reduce the risk specifically in high-risk patients undergoing these procedures, Dr. Szerlip recommended a lower volume of contrast agents. “If I use 50 cc or less of contrast, I rarely see any increase in creatinine. But, if it's a complicated procedure with 300 cc of contrast, I most likely will see an increase in creatinine in high-risk patients,” he said.
Even if you do see a rise in creatinine level after contrast, it may not indicate any lasting damage to the patient's kidneys. “In most cases, any kind of decrement in kidney function is transient and may not necessarily have any long-term implications,” Dr. Weisbord said.
Dr. Palevsky agreed. “In my practice, about one in 10 patients develop an increase in serum creatinine, but most of them do not develop serious long-term consequences from it,” he said.