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Life Extension Magazine

LE Magazine July 2003

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A new method of preventing contrast nephropathy

For years, many patients who elected to undergo coronary angiography risked prolonged hospitalization and renal deterioration as a result of the contrast agents used in the procedure. New research has revealed that the antioxidant acetylcysteine may help to prevent this potentially life-threatening toxic damage.

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Contrast nephropathy is the deterioration of renal function following coronary angiography and intervention and has long been associated with prolonged hospitalization and adverse clinical outcomes. "Contrast nephropathy is a recognized complication of coronary angiography," wrote researchers in the February 5, 2003 issue of JAMA. "It is reported that 14.5% of patients develop a 25% increase in serum creatinine levels following cardiac catheterization. This problem assumes greater and greater importance with increased use of invasive radiological procedures to diagnose and treat coronary artery disease."

Although the disease occurs infrequently with normal renal function, its frequency increases with decreasing renal function, ranging from 5% in patients with mild renal insufficiency to as high as 50% in those with severe renal dysfunction and diabetes [JAMA 2003 Feb 5;289(5):553-8].

Previous studies have attempted to identify methods to reduce the incidence of contrast nephropathy, particularly in high-risk groups. Pretreatment with diuretics, such as furosemide or drugs thought to prevent vasoconstriction, such as calcium channel blockers have not provided clear benefit and may even be harmful [JAMA 2003 Feb 5;289(5):553-8].

Because acetylcysteine has well-established antioxidant properties, researchers speculate that it could in fact protect against oxidative-mediated contrast nephropathy. "Several randomized trials have demonstrated a 40% or greater decrease in the incidence of the disease among patients with chronic renal insufficiency who received contrast agents while undergoing computed tomography as well as cardiac catheterization," wrote Dr. Gary C. Curhan in JAMA. "However, other studies have found no benefit. These discrepancies may be due to differences in the timing and dose of acetylcysteine, total amount of contrast administered, characteristics of patients and the definition of contrast nephropathy."

In a recent prospective randomized clinical trial, researchers in Hong Kong reported on the use of acetylcysteine in patients undergoing cardiac catheterization. For that study, 200 Chinese patients with mild to moderate chronic renal insufficiency were randomly assigned to receive either placebo or acetylcysteine at 600 mg orally twice daily for a total of three doses prior to the procedure and one dose after the procedure. Serum creatinine levels were measured at admission, at 24 and 48 hours, and at day seven. Contrast nephropathy was defined as a greater than 25% increase in serum creatinine concentration within 48 hours after exposure to the contrast agent.

According to their results, contrast nephropathy developed significantly more frequently in the control group (12%) than in the acetylcysteine group (4%). In addition, the average length of hospitalization was 0.5 days shorter in the acetylcysteine group. Furthermore, the serum creatinine concentration decreased significantly after angiography in the acetylcysteine group, from 1.35 to 1.22 mg/dL at two days after the administration of the contrast medium. In the control group, the change in mean serum creatinine concentration was from 1.36 to 1.38 mg/dL and was considered "not significant." These results suggests that acetylcysteine may prevent contrast nephrotoxicity in patients with moderate chronic renal insufficiency undergoing coronary diagnostic and/or interventional procedures.

"Oral acetylcysteine is a safe, effective and inexpensive prophylactic treatment against acute renal dysfunction for patients with moderate chronic renal insufficiency undergoing coronary angiographic procedures with minimal adverse effects and at a low cost," the authors concluded.

Homocysteine and cancer

Homocysteine is a potentially toxic byproduct of the body's metabolism of the amino acid, methionine. Methionine is found in protein, particularly meat protein. Elevated levels of homocysteine are associated with an increased risk for heart attack and stroke.

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New research indicates that elevated homocysteine in the blood is also associated with cancer. Researchers at the University of Utah and Chang Gung Hospital in Taiwan report that cancer cells release high amounts of homocysteine. They also discovered that levels of homocysteine track with cancer biomarkers. When cancer is treated with drugs that kill it, homocysteine levels fall. Researchers believe that homocysteine is indicative of rapidly-dividing cells, i.e., cancer cells. If verified by other researchers, homocysteine could be used in the future as a more sensitive biomarker than those presently in use since it only indicates the presence of living cancer cells, whereas traditional biomarkers appear to indicate both living and dead. For this reason, homocysteine levels may be a more reliable indicator of whether an anticancer treatment is working.

Research from the National Cancer Institute supports the notion that elevated levels of homocysteine may indicate that cancer is present. In a study on women with invasive cervical cancer, those with homocysteine levels greater than 6.31 micromoles per liter of blood were two to three times more likely to have the disease. Interestingly, a lack of folate did not increase the risk in this study, which may mean that other homocysteine-lowering vitamins such as B12, B6 or riboflavin are deficient in women with cervical cancer. Another possibility is that methylation (which lowers homocysteine and reduces the risk for cancer) is compromised in some other way. Similar studies have been done showing that homocysteine is elevated in colon cancer as well.

The laboratory test for measuring homocysteine levels is widely available. It is already well-known that lowering homocysteine can protect against heart attack and stroke.

-Terri Mitchell

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