Title:Cardio-Renal-Anemia Syndrome: A Link Between Erythropoietin, Dimethylarginine and Homocysteine
VOLUME: 19 ISSUE: 21
Author(s):M. Righetti
Affiliation:A. Uboldo” Hospital, Via Uboldo 21 - 20063 Cernusco s/N (MI), Italy.
Keywords:Erythropoietin, erythropoiesis stimulating agents, asymmetric dimethylarginine, homocysteine, chronic renal failure,
cardiovascular disease, anemia
Abstract:Cardio-renal-anemia syndrome is a combination of heart failure, kidney failure, and anemia. Many advanced chronic kidney
disease patients have both anemia and chronic heart failure. They have often hyperhomocysteinemia, high dimethylarginine values and
low erythropoietin levels. Nephrologists treat advanced chronic kidney disease patients with erythropoiesis stimulating agents to improve
anemia, renal and heart disease. Erythropoiesis stimulating agents, though considered essential to improve anemia in chronic kidney
disease patients, have shown no significant protective effect on cardiovascular disease when used in large clinical trials targeting normal
hemoglobin levels. It is possible that the high amounts of these drugs, given to reach normal hemoglobin values, may have
counterbalanced the positive effect on endothelium obtained with low doses. Many studies have shown that erythropoietin improves
endothelial function in animals with high dimethylarginine levels, lowering asymmetric dimethylarginine and increasing nitric oxide
synthesis. Advanced chronic kidney disease patients have also high homocysteine levels which further reduce endothelial function by
increasing asymmetric dimethylarginine. Homocysteine-lowering vitamin B treatment has been associated to a significant reduction of
cardiovascular disease in advanced chronic kidney disease patients. Low doses of epoetin and B vitamins may improve cardiovascular
morbidity by reducing asymmetric dimethylarginine and by increasing nitric oxide synthase activity. This review analyses the interaction
between erythropoietin, dimethylarginine and homocysteine, and their role in cardio-renal-anemia syndrome.