February 19, 2008
Before a CT scan or angiogram, many people should take inexpensive drug to protect kidneys, U-M study finds
Iodine contrast agents that enhance the scans can harm vulnerable kidneys,
but N-acetylcysteine taken beforehand can protect at-risk patients
Ann Arbor, MI – As more and more Americans undergo CT scans and other medical imaging scans involving intense X-rays, a new study suggests that many of them should take a pre-scan drug that could protect their kidneys from damage.
|This top-down view of a patient's abdomen was made using one of U-M's advanced CT scanners and an iodine-containing contrast dye that reflects the CT scanner's X-rays and improves the visibility of certain details. The kidneys are the two gray heart-shaped areas on either side of the spine, which is bright white. Because of the contrast dye, the medulla (inner) part of each kidney can be distinguished from the cortex (outer) part -- a level of detail that can be important in diagnosing disease. But since CT contrast dye can also harm the kidneys of some patients, U-M researchers say many people should receive a drug called N-acetylcysteine before their scans, to protect against such damage.
The inexpensive drug, called N-acetylcysteine, can prevent serious kidney damage that can be caused by the iodine-containing “dyes” that doctors use to enhance the quality of such scans.
That “dye,” called contrast agent, is usually given intravenously before a CT scan, angiogram or other test. But the new study shows that taking an N-acetylcysteine tablet before receiving the contrast agent can protect patients — and that it works better than other medicines that have been proposed for the same purpose.
People whose kidneys are already vulnerable, including many older people and those with diabetes or heart failure, are the most at risk from contrast agents, and have the most to gain from taking the drug.
Researchers from the University of Michigan Health System performed the study, which is published in the Annals of Internal Medicine. It is a meta-analysis of data from 41 randomized controlled studies that evaluated various drugs for their kidney-protecting effects. It was led by Aine Kelly, M.D., M.S., an assistant professor in the Department of Radiology at the U-M Medical School.
Only N-acetylcysteine clearly prevented contrast-induced nephropathy, the medical name for kidney damage caused by contrast agents. Theophylline, another drug that has been seen as a possible kidney-protecting agent, did not reduce risk significantly. Other drugs had no effect, and one, furosemide, raised kidney risk.
“Our goal is to improve the safety and quality of these common tests by studying drugs that reduce the risk of kidney failure,” says senior author Ruth Carlos, M.D., associate professor of radiology.
Mild to moderate kidney damage occurs in one in four high-risk people who have CT scans, and in as many as one in ten people with normal kidney function. In some cases, it causes acute kidney failure.
“Millions of people receive contrast agent each year, including most heart patients who have angioplasties and stents, as well as those having a CT scan. Contrast agent helps physicians see the things we need to see, but it also does pose a hazard to some people,” says Kelly. “This drug, which is quick, convenient, inexpensive and widely available, with no major side effects, appears to be the best choice to protect those whose kidneys are most at risk.”
Only studies that involved intravenous iodine-containing contrast agents, and compared a drug with a water or saline control, were included in the analysis. Oral “milkshake” barium contrast agents, used in CT scans of the digestive system, do not cause kidney damage, and were not included.
The study also did not assess potential ways to protect against kidney damage from gadolinium contrast agents used in MRI (magnetic resonance imaging) scans. Since May 2007, those contrast agents have carried a warning from the U.S. Food and Drug Administration about risk to kidneys.
Kelly, Carlos and their colleagues performed the study to try to get a firm answer to a question that has puzzle medical imaging specialists for years.
Although many drugs have been tried for prevention of iodine-related contrast-induced nephropathy, contradictory evidence has emerged from studies of how well they work. The result has been widespread variation in what hospitals and medical imaging centers do before scanning a patient.
Although a prospective trial comparing N-acetylcysteine directly to other drugs should be conducted to verify the U-M team’s findings, the team hopes its new study will help guide both clinicians and patients.
In fact, Kelly says, patients who know they have weakened kidneys – also called impaired renal function – should speak up when their doctor orders a CT scan, angiogram or angioplasty, and make sure they get a tablet of N-acetylcysteine beforehand.
And, since most kidney problems cause no symptoms, even healthy people might want to ask their doctors to test their blood creatinine levels before sending them for a scan.
Creatinine levels go up when the kidneys aren’t operating efficiently. Contrast-induced nephropathy is defined as a 25 percent or greater increase in creatinine within 48 hours of receiving contrast agent. The new study evaluated the impact of pre-scan medicines by looking at their impact on patients’ creatinine levels, as a surrogate for kidney function.
The problem of contrast-induced nephropathy is a relatively recent one — a byproduct of the dramatic increase in the use of CT scans and X-ray guided procedures such as angioplasty.
The benefit of these scans is not in question: Intense X-rays can reveal valuable information about injuries, diseases, and patients’ response to treatment. Iodine-containing agents allow doctors to improve the scans even further, giving better “contrast” between the blood vessels and tissue, because X-rays are scattered differently by iodine. But as the iodine is carried by the blood to the kidneys, and filtered out into the urine, the iodine can upset the delicate balance that keeps the kidneys functioning.
In recent years, manufacturers of contrast agents have begun to offer different formulations that may pose less risk to patients’ kidneys. More expensive low-iodine and iodine-free agents are available to especially vulnerable patients, and to people who are allergic to iodine. But for everyone else, medical imaging specialists have tried to find ways to prevent the damage.
N-acetylcysteine is already widely used to clear mucus in cystic fibrosis patients, and to treat overdoses of acetaminophen. It’s also being studied for other uses.
Tablets of prescription-strength N-acetylcysteine are inexpensive – about 25 cents for a 500 milligram tablet – and stocked by most pharmacies. It has few side effects. Over-the-counter supplement forms of the drug should not be used for pre-scan kidney protection.
In addition to Kelly and Carlos, the study’s authors are Ben Dwamena, M.D., and Paul Cronin, M.B.B.Ch., both assistant professors of radiology, and Steven J. Bernstein, M.D., MPH, professor of internal medicine. The study was funded by the National Institutes of Health and the National Cancer Institute, and by Kelly’s GE-Association of University Radiologists Radiology Research Academic Fellowship. None of the authors has financial connections with manufacturers of the drugs or contrast agents studied.
Reference: Annals of Internal Medicine, 19 February 2008, Volume 148 Issue 4
Written by: Kara Gavin
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