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Kidney Int. 2003 Dec;64(6):2291-7.

Plasma concentration of coupling factor 6 and cardiovascular events in patients with end-stage renal disease.

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  • 1The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan.



Plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), is an independent predictor of overall mortality and cardiovascular outcome in hemodialysis patients. However, not only ADMA but also traditional risk factors account for only part of the high cardiovascular morbidity and mortality in these patients. We investigated cross-sectionally the association between coupling factor 6 (CF6), an endogenous inhibitor of prostacyclin synthesis, and cardiovascular events in 95 hemodialysis patients.


Plasma CF6 level was measured by radioimmunoassay, whereas plasma ADMA level by high-performance liquid chromatography (HPLC).


Plasma levels of CF6 and ADMA were threefold higher in hemodialysis patients than in control individuals, and there was a positive correlation between these two compounds (r=0.25, P < 0.05). Plasma CF6 level was positively correlated with serum creatinine level (r=0.36, P < 0.01) and was reduced after dialysis (P < 0.05). Plasma CF6 and ADMA levels were both higher in hemodialysis patients complicating ischemic heart disease (myocardial infarction and/or angina) than in those free of cardiovascular events. In a multiple regression model, plasma CF6 level (r=0.24, P=0.023) and ADMA level (r=0.26, P=0.023) were independently related to the occurrence of ischemic heart disease in hemodialysis patients.


CF6 is a novel risk factor for ischemic heart disease in end-stage renal disease (ESRD). Synergism of this peptide and ADMA might contribute to its occurrence presumably by inhibition of prostacyclin and nitric oxide production. A prospective study is needed to evaluate this issue more precisely.

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