NDT Advance Access originally published online on June 23, 2009
Nephrology Dialysis Transplantation 2009 24(11):3454-3460; doi:10.1093/ndt/gfp309
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Low levels of IgM antibodies against phosphorylcholine-A increase mortality risk in patients undergoing haemodialysis
1 Divisions of Renal Medicine 2 Baxter Novum, Department of Clinical Science, Intervention and Technology 3 Division of Emergency Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
Correspondence and offprint requests to: Peter Stenvinkel; E-mail: peter.stenvinkel{at}ki.se
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Abstract |
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Background. Atherosclerosis is an inflammatory disease where oxidized low-density lipoprotein may play an important role through phosphorylcholine (PC)-exposing inflammatory phospholipids. Both atherosclerosis and its clinical consequence cardiovascular disease (CVD) are highly prevalent in patients with end-stage renal disease (ESRD). We here study the association between IgM antibodies against phosphorylcholine-A (anti-PC) and risk of death in patients undergoing haemodialysis (HD).
Methods. We performed a prospective observational study examining the relationship between anti-PC concentrations and mortality risk in a well-characterized cohort of 203 prevalent HD patients [56% men, median age 66 (interquartile range 51–74) years, vintage time 29 (15–58) months] with a mean follow-up period of 29 (14–58) months.
Results. Median anti-PC levels were lower in HD patients with systemic collagen vascular disease (18.9 versus 45.2 U/mL, P = 0.01) and in patients who died during the follow-up period (29.5 versus 53.9 U/mL; P = 0.0008). The patients with an anti-PC value below the median (42.1 U/mL) had a higher mortality rate with a crude hazard ratio (HR) of 2.13 (95% CI 1.40–3.22). These patients remained at higher risk of death (HR 1.76; 95% CI 1.13–2.74) even after adjustment for traditional risk factors (age, sex, smoking habits, CKD aetiology, CVD and diabetes), protein-energy wasting and inflammation (HR 1.70; 95% CI 1.19–2.68).
Conclusion. Low levels of natural IgM antibodies against PC are independent predictors of death among HD patients. Further studies are needed to define the clinical role of such measurements and to explore potentials for active immunization, with PC as an antigen, or passive immunization, aiming at raising levels of protective anti-PC.
Keywords: atherosclerosis; haemodialysis; inflammation; IL-6; phosporylcholine
*Both authors equally contributed.
Received for publication: 20. 1.09
Accepted in revised form: 3. 6.09