The Optimal Haemoglobin Target in Dialysis Patients May Be Determined by Its Contrasting Effects on Arterial Stiffness and Pressure Pulsatility

Introduction: It remains unclear why the optimal haemoglobin target is lower in patients with chronic kidney disease (CKD) than in non-CKD persons. Arteriosclerosis and consequent impaired arterial function comprise a central cardiovascular risk mechanism in CKD. We hypothesized that the optimal haemoglobin target depends on its opposing effects on arterial stiffness and pressure pulsatility in CKD.

Methods: Arterial stiffness (aortic pulse wave velocity), wave reflection (augmentation index, reflected wave pressure and reflection magnitude), and pressure pulsatility (central systolic and pulse pressure, peripheral pulse pressure, pressure amplification and forward wave pressure) were assessed in 48 dialysis patients.

Results: In established confounder and diabetes adjusted linear regression models, haemoglobin levels were directly associated with arterial stiffness (partial R=0.366, p=0.03) and inversely with central systolic pressure (partial R=-0.344, p=0.04), central pulse pressure (partial R=-0.403, p=0.01), peripheral pulse pressure (partial R=-0.521, p=0.001) and forward wave pressure (partial R=-0.544, p=0.001). The presence of heart failure and use of angiotensin converting enzyme inhibitors or angiotensin receptor blockers and erythropoietin stimulating agents did not materially alter these relationships upon further adjustment for the respective characteristics in the models, and in sensitivity analyses. In receiver operator characteristic curve analysis, the optimal haemoglobin concentration cut-off values in predicting arterial stiffness and increased central pulse pressure were remarkably similar at 10.95 g/dl and 10.85 g/dl, respectively, and with clinically useful sensitivities, specificities and positive and negative predictive values. In logistic regression models, a haemoglobin value of >10.9 mg/dl was associated with both arterial stiffness (>10 m/sec; OR (95% CI) = 10.48 (1.57-70.08), p=0.02) and normal central pulse pressure (>50 mmHg; OR (95% CI) = 7.55 (1.58-36.03), p=0.01).

Conclusion: This study suggests that the optimal haemoglobin target in dialysis patients is ~11g/dl and determined by its differential and contrasting effects on arterial stiffness and pressure pulsatility.