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(Circulation. 2004;109:369-374.)
© 2004 American Heart Association, Inc.

Clinical Investigation and Reports

Acetylcysteine Reduces Plasma Homocysteine Concentration and Improves Pulse Pressure and Endothelial Function in Patients With End-Stage Renal Failure

Alexandra Scholze, MD; Christiane Rinder; Joachim Beige, MD; Reiner Riezler, MD; Walter Zidek, MD; Martin Tepel, MD

From Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Med. Klinik IV (A.S., C.R., J.B., W.Z., M.T.), Berlin, and Severi-Med (R.R.), Muenster, Germany.

Correspondence to Dr Martin Tepel, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Med. Klinik IV, Hindenburgdamm 30, D-12200 Berlin, Germany. E-mail Tepel{at}zedat.fu-berlin.de

Received June 6, 2003; de novo received August 13, 2003; revision received October 10, 2003; accepted October 13, 2003.

Background— Increased oxidative stress, elevated plasma homocysteine concentration, increased pulse pressure, and impaired endothelial function constitute risk factors for increased mortality in patients with end-stage renal failure.

Methods and Results— We investigated the metabolic and hemodynamic effects of intravenous administration of acetylcysteine, a thiol-containing antioxidant, during a hemodialysis session in a prospective, randomized, placebo-controlled crossover study in 20 patients with end-stage renal failure. Under control conditions, a hemodialysis session reduced plasma homocysteine concentration to 58±22% predialysis (mean±SD), whereas in the presence of acetylcysteine, the plasma homocysteine concentration was significantly more reduced to 12±7% predialysis (P<0.01). The reduction of plasma homocysteine concentration was significantly correlated with a reduction of pulse pressure. A 10% decrease in plasma homocysteine concentration was associated with a decrease of pulse pressure by 2.5 mm Hg. Analysis of the second derivative of photoplethysmogram waveform showed changes of arterial wave reflectance during hemodialysis in the presence of acetylcysteine, indicating improved endothelial function.

Conclusions— Acetylcysteine-dependent increase of homocysteine removal during a hemodialysis session improves plasma homocysteine concentration, pulse pressure, and endothelial function in patients with end-stage renal failure.

Key Words: antioxidants • drugs • endothelium • risk factors

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