Introduction Erythropoiesis-Stimulating Brokers (ESA) are hypothesized to increase cardiovascular mortality in

Introduction Erythropoiesis-Stimulating Brokers (ESA) are hypothesized to increase cardiovascular mortality in patients with chronic kidney disease. mellitus and estimated glomerular filtration rate. Results At baseline 95.6% of patients with ESA were treated with antihypertensive medication and 73.1% of patients without ESA. No relevant difference in BP was found. During pre-dialysis care patients with ESA used 0.77 (95% CI 0.63;0.91) more classes of antihypertensive drugs. The adjusted difference in systolic blood pressure (SBP) was ?0.3 (95% CI ?2.7;2.0) mmHg and in diastolic blood pressure (DBP) was ?1.0 (95% CI ?2.1;0.3) mmHg for patients with ESA compared to patients without ESA. Adjusted SBP was 3.7 (95% CI ?1.6;9.0) mmHg higher in patients with a high ESA dose compared to patients with a low ESA dose. Conclusions Our study confirms the hypertensive effect of ESA since ESA treated patients received more antihypertensive agents. However no relevant difference in BP was found between patients with and without ESA thus the increase in BP seems to be controlled for by antihypertensive medication. Introduction Hypertension is present in 71-95% of adult patients with chronic kidney disease (CKD) [1]-[4]. High blood pressure (BP) is usually a major risk factor for cardiovascular morbidity and mortality [5] and is associated with an increased loss of renal function [6]. Therefore guidelines recommend a BP Etoposide control to less than 130/80 mmHg for patients with CKD [7]-[9]. With declining renal function endogenous erythropoietin production decreases and the majority of CKD patients will be treated with erythropoiesis-stimulating brokers (ESAs) for Itgal their anemia. However recently several anemia-correction trials in pre-dialysis patients have exhibited that patients randomized to achieve normal hemoglobin levels experience more cardiovascular events or a higher mortality rate [10]-[12]. These patients were Etoposide treated with higher ESA doses than patients assigned to the lower hemoglobin arm. Some observational studies have also shown an increased all-cause and cardiovascular mortality in dialysis patients treated with higher ESA doses [13] [14]. The mechanism responsible for these extra cardiovascular events and mortality is not entirely clarified. Several hypotheses have been proposed but the elevation of BP by ESAs thereby increasing the risk Etoposide of cardiovascular events is one of the most important theories [15] [16]. Indeed ESA induced hypertension has already been reported at the introduction of ESAs late 1980s in 10-32% of hemodialysis patients [17]-[19]. However since then nephrologists have learned to slowly increase hemoglobin with lower ESA doses to avoid these side effects. Prior studies have also not consistently identified differences in BP in patients randomized to higher versus lower hemoglobin targets [11] [12] [20] [21]. In clinical practice actual BP can remain stable during ESA treatment with or without adjustments in antihypertensive medication [19] [22]. Data on BP control is limited in patients with CKD and the available studies underrepresent the pre-dialysis patients [2]-[4] [23]-[25]. Most importantly information about the influence of ESA therapy and especially high doses of ESA therapy on BP is usually lacking. Therefore we aimed to determine whether the use of ESA was associated with antihypertensive treatment and higher BP. Materials and Methods Study Design and Populace The PREdialysis Individual REcord (PREPARE-2) study is usually a prospective follow-up study of incident pre-dialysis patients Etoposide treated in 25 nephrology outpatient clinics in the Netherlands. Patients of at least eighteen years of age were included at the start of specialized pre-dialysis care between July 2004 and June 2011. In practice this refers Etoposide to incident pre-dialysis patients with an estimated glomerular filtration rate (eGFR) of less than 20-30 mL/min/1.73 m2 in whom renal function loss is progressive. Patients with a failing kidney transplant were also included in the study if the Etoposide transplantation was at least one year ago. All participants gave their written informed consent prior to study inclusion. The patients were treated by their nephrologists in their regular plan according to the treatment guideline of the Dutch Federation of Nephrology [26] a Dutch guideline based on the KDOQI guidelines [7] [27]. Clinical data had been collected in the beginning of specific pre-dialysis treatment and in following 6-month intervals. Individuals were followed before start.