Erythropoietin and systemic hypertension.

Systemic hypertension has been reported to develop, or to worsen, in 20-30% of patients treated with recombinant human erythropoietin (r-HuEPO) worldwide. The greatest increases in blood pressure affect day-time systolic and night-time diastolic blood pressure. Hypertension may develop in some patients as early as 2 weeks and in others as late as 4 months after the start of r-HuEPO treatment. In haemodialysis patients with systemic hypotension, r-HuEPO usually induces a 10% increase in blood pressure, with no significant change in the frequency of hypotensive episodes. Several risk factors for the development, or worsening, of hypertension after r-HuEPO therapy have been identified. They include the presence of pre-existing hypertension, rapid increase in haematocrit, a low baseline haematocrit before r-HuEPO administration, high doses and i.v. route of administration, the presence of native kidneys, a genetic predisposition to hypertension, and possibly a younger age. There are several potential mechanisms by which r-HuEPO therapy may increase blood pressure in haemodialysis patients. They include increased blood viscosity; the loss of hypoxic vasodilation; the activation of neurohumoral systems (catecholamines, the renin-angiotensin system); and especially a direct vascular effect. This last mechanism is supported by several data, and many factors may be involved in its pathogenesis (an increased cell calcium uptake; an imbalance in local vasoactive agents, with increased synthesis of ET-1; a mitogenic effect; and a platelet-dependent mechanism).