Cysteine, homocysteine and their redox status as a predictor of death in patients on hemodialysis

Abstract

Introduction. Chronic kidney disease (CKD), especially its end stage, that requires renal replacement therapy, is characterized by high cardiovascular morbidity and mortality. Uremic syndrome associated with CKD facilitates oxidative stress, endothelial dysfunction, and inflammation and, thereby, plays a key role in the development of cardiovascular complications. Cysteine and homocysteine form a thiol-disulfide system in a state of dynamic equilibrium. The imbalance between reduced and oxidized forms of these aminothiols may reflect the degree of oxidative stress and its contribution to the development of CKD complications. The aim of this study was to identify the prognostic role of cysteine, homocysteine and their redox status in blood plasma of patients with terminal renal insufficiency. Methods. The study included 47 patients who received renal replacement therapy (hemodialysis) for at least 3 months prior to blood sampling. The follow-up period was 3 years. Results. It was found that a high level of total content of cysteine and homocysteine, a low level of their reduced forms, and a low redox status of cysteine (<1%) and homocysteine (<6%) are independent predictors of death in hemodialysis patients (odds ratio 4.7 and 4.8, respectively, p< 0.05). An increase in the plasma pool of homocysteine due to its insufficient utilization by the kidneys leads to an increase in its cellular concentration and activation of trans-sulfurization enzymes that convert homocysteine into cysteine. This contributes to an elevation of plasma cysteine. Disorders of homocysteine metabolism are not only evident as increased total cysteine content but also affect the thiol-disulfide balance of aminothiols. Conclusion. The total content, reduced forms, and redox status of cysteine and homocysteine are independent predictors of death in hemodialysis patients. Assessment of the redox status can be useful for risk stratification and the development of personalized therapeutic strategies for restricting oxidative stress and improving prognosis in this category of patients. Further studies are needed to evaluate the effectiveness of antioxidant therapy and other interventions aimed at the correction of the redox balance in hemodialysis patients.