Erythropoietin and Cardiovascular Risk

Abstract

We studied the changes in some cardiovascular risk (CVR) factors in 24 maintenance hemodialysis patients treated for 1 year with recombinant human erythropoietin (rHuEPO) either intravenously (12 cases) or subcutaneously (12 cases). In order to clarify whether changes in some parameters were due to direct action of rHuEPO or to changes in food intake, we divided the patients into two groups: group A was formed by 14 patients who showed an increase in their food intake during rHuEPO therapy and group B by 10 patients without or with slight changes in their food intake. rHuEPO induced an improvement in well-being in 20 of 24 patients and in physical working capacity in 14 of 24, an increase in mean blood pressure in all patients, and hypertension in 4 of 24 patients. The incidence of hypertension was slightly higher after intravenous (3/12) than after subcutaneous (1/12) treatment. The rate of dialysis treatment with symptomatic hypertension significantly decreased from 44.0 ± 8.0 to 12.1 ± 2.2% after intravenous and from 41.3 ± 6.8to 10.0 ± 3.8% after subcutaneous treatment. Evaluation of glucose metabolism (intravenous glucose tolerance test) before and after 3 months of rHuEPO therapy showed an improvement in glucose utilization (insulin resistance reduction). Cholesterol (CH), low-density lipoprotein CH, triglycerides, and apolipoprotein B significantly increased in group A, but not in group B. Both in groups A and B, high-density lipoprotein CH significantly decreased during the first 6 months and returned to basal values during the following months, and the apolipoprotein Al level significantly decreased during the first 4 months and increased to levels higher than basal values during the following months. Changes in CH and apolipoprotein B were also positively correlated with changes in the protein catabolic rate. We infer that rHuEPO has opposite effects on CVR, but subcutaneous administration, dietary control, and antihypertensive treatment may produce a net decrease in CVR of maintenance hemodialysis patients on rHuEPO therapy.

Memory Improvement in the AβPP/PS1 Mouse Model of Familial Alzheimer's Disease Induced by Carbamylated-Erythropoietin is Accompanied by Modulation of Synaptic Genes

“…Side effects of chronic EPO administration related to cardiovascular risk factors [14,15] and thrombocytopenia [16] reduce the clinical applicability of EPO as a neuroprotective agent [17]. This has prompted the search for molecules that do not have erythropoietic activity but conserve protective functions.…”

Glucose-Induced Insulin Secretion in Uremia: Relation with Acid-Base Balance and Effects of Bicarbonate Administration

“…If pa tients are not divided into groups according to their acidosis degree, this result cannot be evidenced because of the great variability of Rl values. In a previous investigation [26], in 11 uremic patients selected according to different criteria, we found no significant changes in glucose metabolism param eters after bicarbonate administration.…”

“…Indeed, in vitro studies demonstrated that pH and bicarbonate con centration may influence insulin secretion [12][13][14][15][16][17][18] and in sulin binding to receptors [19][20][21][22]. However, in the lit erature, there are few and contrasting reports [23][24][25][26] on effects of metabolic acidosis on glucose metabolism in uremic patients.…”

Effect of Erythropoietin Therapy on Serum Apolipoprotein A1 Levels in Patients Undergoing Chronic Peritoneal Dialysis

“…Alternatively, the decrease in insulin resistance and, probably, increase in hepatic synthesis of ApoA1 associated with EPO treatment may account for the elevated ApoA1 levels in PD patients. Several studies in the HD population have showed a significant increase in serum ApoA1 concentrations during long-term EPO treatment (4,6,8,10), suggesting that EPO treatment is responsible for this improvement. We have extended this observation to patients undergoing PD, in whom serum ApoA1 concentrations were positively correlated with subcutaneous weekly EPO doses.…”