The relationship of haemoglobin level and survival: direct or indirect effects?

The relationship between haemoglobin (Hb) level and survival in patients with chronic kidney disease (CKD) is complex. This paper explores the physiological basis for the hypothesis that Hb level and survival are causally related in this patient group, and assesses the current state of knowledge from clinical studies. Issues related to the methodology and analysis of clinical studies limit the certainty with which conclusions regarding the direct relationship between Hb level and survival can be drawn. The data support the concepts that Hb level is associated with survival in patients both with and without CKD, that changes in Hb level are associated with cardiovascular disease (CVD), and that CVD is prevalent in patients with CKD. Hb level is affected by nutritional status, inflammation, and the availability and effectiveness of human recombinant erythropoietin (rHuEPO) therapy, as well as by the degree of kidney function. Thus, the complexity of the relationships between Hb level, CVD and survival in patients with CKD requires further study from both the mechanistic and the clinical perspective. Properly designed clinical trials with survival as an endpoint, as well as data from prospectively measured modifiers of Hb levels and other markers of CVD, are needed to determine the physiological and statistical interaction of these factors in clinical practice.