Abstract 18002: S-adenosylhomocysteine Levels May Better Differentiate Between Normal Control, Subjects With Ckd Stages 3 and 4, and Subjects on Hemodialysis
Patients on hemodialysis have higher levels of plasma total homocysteine (tHcy) and are at higher risk for atherosclerotic cardiovascular and vascular events, including death. However, secondary prevention trials to date have not shown any reduction in recurrent atherosclerotic events with B vitamin supplementation that lowers tHcy levels. Because high tHcy levels are still a good predictor of CV events, we investigated whether other metabolites related to tHcy metabolism and the methylation cycle may be altered in subjects at various stages of chronic kidney disease.
Methods: We measured 6 intermediates of the methylation cycle in plasma using liquid chromatography mass spectroscopy: tHcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), cystathionine, asymmetric dimethylarginine (ADMA), and symmetric dimethylargine (SDMA). Subjects included 92 subjects enrolled in longitudinal studies of healthy aging and dementia (Controls), 21 subjects with chronic kidney disease stages 3 and 4 (CKD), and 25 subjects on hemodialysis (Dialysis). All samples were collected between 2004 and 2012.
Results: T-test analysis (corrected for multiplicity using Bonferoni correction) results show that all 6 metabolites were statistically significantly higher (p-values <0.05) in the CKD subjects than the Controls, and again statistically significantly higher (p-values <0.05) in Dialysis subjects than in CKD subjects (see Figure). While ADMA may be an independent risk factor for CAD, both tHcy and SAH levels were the most discriminatory: tHcy levels were 2.8 fold higher in CKD and 4 fold higher in Dialysis; SAH levels were 2.9 fold higher in CKD and 8.7 fold higher in Dialysis.
Conclusion: SAH is a potent inhibitor of methylation reactions and has been implicated in causing vascular pathology. Elevated levels of SAH in plasma may provide greater discrimination in assessing risk of vascular disease in patients with chronic kidney disease.
- © 2013 by American Heart Association, Inc.