High levels of plasma indoxyl sulfate (IS), a protein-bound uremic toxin, are associated with an elevated risk of heart failure, according to a new study.

A team led by Xiao-Qiang Ding, MD, of Fudan University in Shanghai, China, prospectively studied 258 patients with a mean age of 57 years who had been on hemodialysis (HD) for more than 6 months. The researchers categorized patients into 2 groups: a low-IS group (32.35 µg/mL or less) and a high-IS group (greater than 32.35 ug/mL) and followed them for a median of 48 months.

During follow-up, 68 patients experienced episodes of first heart failure. After adjusting for confounding factors, compared with patients in the low-indoxyl sulfate group, those in the high-indoxyl sulfate group had a significant 5.3-fold increased risk of a first heart failure event, Dr. Ding and colleagues reported online ahead of print in the Clinical Journal of the American Society of Nephrology. Each 1 µg/mL increment in indoxyl sulfate was associated with a significant 4% increased risk of a first heart failure.

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The authors noted that in recent years, more and more attention has been paid to the relationship between IS and cardiovascular disease and chronic kidney disease.

For example, a study of 70 pre-dialysis patients led by Chih-Jen Wu, MD, PhD, of Mackay Memorial Hospital in Taipei, Taiwan,  found that serum IS predicted cardiovascular cardiovascular events, according to a report in the Archives of Medical Research (2012;43:451–456). A team led by I-Ting Tsai, MD, of I-Shou University, Kaohsiung, Taiwan, reported in Clinical and Investigative Medicine (2013;36:E42–E49) that patients with significant coronary artery stenosis had significantly higher serum IS levels than patients with normal coronary arteries.

On multivariate analysis, serum IS levels were independently associated with the presence and severity of coronary artery disease. A prospective study of 521 HD patients in the U.S. by Michal L. Melamed, MD, of Albert Einstein College of Medicine, Bronx, N.Y., and colleagues found that elevated plasma IS was associated with a significant 30% increased risk of all-cause mortality, but was not associated with cardiovascular mortality, according to a paper published in BMC Nephrology (2013;14:134–143).