Association between Erythropoietin Requirements and Antihypertensive Agents

Abstract

Background: Angiotensin-converting enzyme inhibitors (ACI) and angiotensin II receptor blockers (ARB) have been reported to increase recombinant human erythropoietin (rHuEPO) requirements. We performed a cross-sectional study to investigate an association of antihypertensive agents including these two with the rHuEPO dose in chronic hemodialysis patients. Methods: We studied 625 patients undergoing hemodialysis therapy in 11 dialysis units. The association between the rHuEPO dose and antihypertensive agents was statistically analyzed. Results: The mean hemoglobin (Hb) level and rHuEPO dose corrected by body weight were 10.5 g/dl and 95.2 U/kg/week, respectively. When the patients were subdivided into four groups according to the number of prescribed antihypertensive agents (G-0, G-1, G-2, and G-3; patients prescribed with no medication, 1, 2, and >3 drugs, respectively), a significantly low dose of rHuEPO was observed in G-0 compared to the other groups. Unpaired t test showed a higher dose of rHuEPO in the presence of ARB, α-blockers, or calcium channel blockers (CCB). The rHuEPO dose was higher in the elderly, in females, and in patients with diabetes or hypertension. In multiple regression analysis, age, sex, rHuEPO dose, serum albumin level, and duration of dialysis therapy but not antihypertensive drugs were independent factors for the Hb level. In contrast, the rHuEPO dose was significantly associated with a low level of Hb, age, females, and CCB use. However, since CCB use was strongly associated not only with rHuEPO dose but also with systolic blood pressure and the use of α-blockers and ARB, these findings might be caused by erythropoietin (EPO)-induced hypertension. Conclusion: There was an association between the number of antihypertensive agents and rHuEPO dose in chronic hemodialysis patients. However, no significant relation was indicated between ARB/ACI use and EPO requirements.

Erythropoietin Protects against Local Anesthetic Myotoxicity during Continuous Regional Analgesia

“…42 Moreover, our findings suggest that the mitochondrial protective effects of rhEPO should be carefully evaluated in the general context of mitochondrial pathologic dysfunction. 47,48 rhEPO utilization at high doses or for long periods of time, however, requires rigorous and continuous evaluation during treatment to assess the risk of hypertension, 49 venous thromboembolism, and mortality, which are routinely described in the elderly and in patients with cancer. 50 The risk of rhEPO side effects combined to the extremely high cost of rhEPO has to be considered when minor clinical implications such as bupivacaine-induced myotoxicity are being discussed.…”

Lisinopril pharmacokinetics and erythropoietin requirement in haemodialysis patients

“…As first reported in 1984 [19], this effect was supported by many studies [20][21][22][23][24]. However, there are also data arguing that ACE-I do not affect erythropoietin (EPO) efficacy in haemodialysis patients [14,[25][26][27][28]. Although this is an ongoing debate, in our opinion there has never been a study with the ideal design that would include a long-term, high-dose use of an ACE-I with exclusive renal elimination in a haemodialysis population.…”

“…There is also an ongoing discussion whether use of ACE-I contributes to this hyporesponsiveness. However, there is also a significant volume of contradicting data [14,[25][26][27][28]. Because it is eliminated entirely via renal clearance without a prior metabolism, it accumulates in dialysis patients.…”

“…The suggested mechanisms varied from abolition of endogenous erythropoietin release by reduction in plasma levels of erythrogenic factors (angiotensin II, insulin like growth factor 1) to reduction in the sensitivity to recombinant human erythropoietin and increase in plasma levels of the tetrapeptide N-acetyl-seryl-aspartyllysyl-proline, which prevents the recruitment of pluripotent hemopoietic stem cells [13,14]. However, there is also a significant volume of contradicting data [14,[25][26][27][28].…”

“…This issue has been the subject of controversy in the scientific literature as one of the undesirable effects of ACE-I [3,11,[13][14][15][16][17][18]. However, there are also data arguing that ACE-I do not affect erythropoietin (EPO) efficacy in haemodialysis patients [14,[25][26][27][28]. However, there are also data arguing that ACE-I do not affect erythropoietin (EPO) efficacy in haemodialysis patients [14,[25][26][27][28].…”