Current Pharmaceutical Biotechnology                Bartnicki Piotr * , Stępień Mariusz and Rysz Jacek Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland A R T I C L E H I S T O R Y Received: September 15, 2016 Revised: November 22, 2016 Accepted: January 23, 2017 DOI: 10.2174/1389201018666170127104801 Abstract: Chronic kidney disease (CKD) is an important health problem, because of unsuccessful out- comes such as CKD progression to end stage renal disease and high risk of cardiovascular disease (CVD). Anemia, associated with CKD, is considered a non-traditional risk factor for CVD which may contribute to faster CKD progression. Anemia treatment with erythropoiesis-stimulating agents (ESAs) seems to exert non-hematopoietic effects on different tissues and organs, including cardiovascular sys- tem and kidneys. On the other hand, clinical use of high doses of short-acting ESAs and higher target hemoglobin level were associated with higher risk of CVD. Literature data indicate the usefulness of long-acting ESAs in treatment of anemia in non-dialysis CKD patients. In particular, continuous erythropoietin receptor activator seems to be a good choice in these patients because of its efficiency, safety and monthly administration. Continuous but slower erythropoietin receptor activation, using methoxy polyethylene glycol-epoetin beta (MPG-EPO), administered once a month, slowly corrects anemia without exceeding the recommended hemoglobin level. An overview of the available literature may suggest nephroprotective and cardiovascular protective effects of MPG-EPO. It seems possible that anemia treatment with a novel ESAs, MPG-EPO in early stages of CKD may reduce CVD risk in these patients and delay CKD progression. This review of available literature evaluates the correlation between continuous erythropoietin receptor activation using MPG-EPO and CKD progression and CVD risk in non-dialysis CKD patients. Keywords: Erythropoietin, methoxy polyethylene glycol-epoetin beta, continuous erythropoietin receptor activator, chronic kidney disease, anemia. 1. INTRODUCTION Chronic kidney disease (CKD) is a very important health problem. The prevalence of CKD is estimated at about 10- 12% of the general population [1, 2]. The most important unsuccessful outcomes of CKD are progressive loss of renal function to end stage renal disease (ESRD) and cardiovascu- lar disease (CVD), which is the most common cause of death in CKD patients [3]. In these patients’ premature atheroscle- rosis occurs, which may lead to hypertension, coronary heart disease, myocardial infarction and as a consequence to heart failure [4]. Traditional risk factors of atherosclerosis do not fully explain these disadvantageous changes in the cardio- vascular system [5, 6]. The importance of non-traditional risk factors of premature atherosclerosis and CVD in CKD patients has been postulated; these include anemia, calcium- phosphate disorders, hyperparathyroidism, oxidative stress *Address correspondence to this author at the Department of Nephrology, Hypertension and Family Medicine, Zeromski Street 113, 90-596 Lodz, Poland; Tel: +48426393750; Fax: +48426393732; E-mail: piotr.bartnicki@umed.lodz.pl and chronic inflammation, especially in endothelium [7, 8]. Disadvantageous changes in the cardiovascular system may already be present in early stages of CKD, which worsens the prognosis of these patients [9]. Therapeutic interventions, regarding non-traditional risk factors of atherosclerosis and CVD, may be useful in the inhibition of CKD progression, as well as in the reduction of the risk of cardiovascular compli- cations and in consequence result in a better prognosis of these patients [10]. Anemia is very important non-traditional risk factor of cardiovascular complications in CKD patients. Anemia is higher within CKD progression and it worsens patients qualify of life [11]. Anemia may enhance oxidative stress and chronic inflammation and as a consequence may be an important factor in the pathogenesis of premature athe- rosclerosis and CVD [12, 13]. It is believed that anemia may contribute to faster CKD progression to ESRD when patients require dialysis treatment [14]. Anemia treatment with erythropoiesis-stimulating agents (ESAs), apart from anemia correction and better quality of life of CKD patients, seems to slow down CKD progression, reduce the risk of CVD and enhance prognosis of CKD patients, especially when the 1873-4316/17 $58.00+.00 © 2017 Bentham Science Publishers Send Orders for Reprints to reprints@benthamscience.ae Current Pharmaceutical Biotechnology, 2017, 18, 303-308 303 REVIEW ARTICLE Methoxy Polyethylene Glycol-Epoetin Beta as a Novel Erythropoiesis Stimulating Agent with Possible Nephroprotective and Cardiovascular Protective Effects in Non-Dialysis Chronic Kidney Disease Patients