Effect of erythropoietin on cardiovascular prognosis parameters in hemodialysis patients

Abstract

Background: Renal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients. In addition, an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patients with end-stage renal disease (ESRD).

Methods: We investigated in this prospective longitudinal study the effect of hemoglobin normalization by a chronic treatment with recombinant human erythropoietin (rhEPO) on cardiovascular prognosis parameters in 23 patients on chronic hemodialysis with renal anemia (hemoglobin concentration < or =10.5 g/dL) and echocardiographically proven left ventricular hypertrophy. We studied muscle sympathetic nerve activity measured by microneurography; cardiopulmonary baroreflex activity by lower-body negative pressure (LBNP-) testing; left ventricular structure and mass index (LVMI) by echocardiography; blood pressure by 24-hour readings; peripheral blood flow and vascular resistance by plethysmography before (U1) and after 7 months of chronic rhEPO treatment (U2).

Results: In the anemic state, mean (+/- SD) muscle sympathetic nerve activity in ESRD was elevated (U1 rest, 34 +/- 13 bursts per minute) and cardiopulmonary baroreflex response during LBNP markedly lacking (U1 -15 mm Hg, 34 +/- 13 bursts per minute) reflecting a severely impaired autonomic function. Normalization of the hemoglobin concentration by chronic rhEPO treatment (U1, 10.5 +/- 0.9 g/dL versus U2, 13.4 +/- 3.1 g/dL, P <0.001) did not influence sympathetic nerve activity (U2, 34 +/- 15 bursts per minute, NS) and cardiopulmonary baroreflex sensitivity did not change (U2 -15 mm Hg, 37 +/- 16 bursts per minute, NS). LVMI decreased significantly after chronic treatment with rhEPO (U1, 134 +/- 26 g/m2 versus U2, 97 +/- 25 g/m2, P < 0.001) and left ventricular geometry developed from an asymmetric to a symmetric configuration (U1, relative wall thickness 0.58 versus U2, 0.43, P < 0.001). Under treatment with rhEPO, 24-hour systolic and diastolic blood pressure did not increase (systolic U1, 132 +/- 4 mm Hg versus U2, 128 +/- 3 mm Hg, NS, and diastolic U1, 76 +/- 2 mm Hg versus U2, 73 +/- 2 mm Hg, NS). Peripheral blood flow (U1, 6.1 +/- 3.3 mL/100 mL/min versus U2, 6.2 +/- 0.6 mL/100 mL/min, NS) as well as forearm vascular resistance (U1, 15.7 +/- 3.3 mm Hg/mL/100 mL versus U2, 14.9 +/- 3.1 mm Hg/mL/100 mL, NS) did not change by chronic rhEPO treatment.

Conclusion: Normalization of hemoglobin by chronic rhEPO treatment in dialysis patients has beneficial cardiovascular effects with regression of left ventricular hypertrophy and improvement of left ventricular geometry. However, a reduction of sympathetic overactivity or a resetting of baroreceptor sensitivity by a rhEPO treatment in dialysis patients in the medium-term could not be demonstrated. The reason for this may be the complex and multifactorial pathomechanism of autonomic dysfunction and cardiovascular disease in ESRD.