Received June 4, 2007
Accepted on September 19, 2007

ORIGINAL ARTICLES

Association between Serum ₂-Microglobulin Level and Infectious Mortality in Hemodialysis Patients

Alfred K. Cheung ^*1, Tom Greene , John K. Leypoldt , Guofen Yan , Michael Allon ^||, James Delmez ^¶, Andrew S. Levey ^**, Nathan W. Levin , Michael V. Rocco , Gerald Schulman , Garabed Eknoyan ^||||, and for HEMO Study Group

*Medical Service and Research Service, Veterans Affairs Salt Lake City Healthcare System and Department of Medicine, University of Utah, Salt Lake City, Utah; Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia; ||Department of Medicine, University of Alabama, Birmingham, Alabama; ¶Department of Medicine, Washington University, St. Louis, Missouri; **Division of Nephrology, New England Medical Center, Boston, Massachusetts; Department of Medicine, Beth Israel Medical Center, New York, New York; Department of Internal Medicine, Wake Forest University, Winston-Salem, North Carolina; Department of Medicine, Vanderbilt University, Nashville, Tennesee; and ||||Department of Medicine, Baylor College of Medicine, Houston, Texas

¹ To whom correspondence should be addressed. E-mail: alfred.cheung{at}hsc.utah.edu.

	Abstract

Background and objectives: Secondary analysis of the Hemodialysis Study showed that serum ₂-microglobulin levels predicted all-cause mortality and that high-flux dialysis was associated with decreased cardiac deaths in hemodialysis patients. This study examined the association of serum ₂-microglobulin levels and dialyzer ₂-microglobulin kinetics with the two most common causes of deaths: Cardiac and infectious diseases.

Cox regression analyses were performed to relate cardiac or infectious deaths to cumulative mean follow-up predialysis serum ₂-microglobulin levels while controlling for baseline demographics, comorbidity, residual kidney function, and dialysis-related variables.

Results: The cohort of 1813 patients experienced 180 infectious deaths and 315 cardiac deaths. The adjusted hazard ratio for infectious death was 1.21 (95% confidence interval 1.07 to 1.37) per 10-mg/L increase in ₂-microglobulin. This association was independent of the prestudy years on dialysis. In contrast, the association between serum ₂-microglobulin level and cardiac death was not statistically significant. In similar regression models, higher cumulative mean Kt/V of ₂-microglobulin was not significantly associated with either infectious or cardiac mortality in the full cohort but exhibited trends suggesting an association with lower infectious mortality (relative risk 0.93; 95% confidence interval 0.86 to 1.01, for each 0.1-U increase in ₂-microglobulin Kt/V) and lower cardiac mortality (relative risk 0.93; 95% confidence interval 0.87 to 1.00) in the subgroup with >3.7 prestudy years of dialysis.

Conclusions: These results generally support the notion that middle molecules are associated with systemic toxicity and that their accumulation predisposes dialysis patients to infectious deaths, independent of the duration of maintenance dialysis.