Erythropoietin mimics the acute phase response in critical illness

Abstract

Background: In a prospective observational study, we examined the temporal relationships between serum erythropoietin (EPO) levels, haemoglobin concentration and the inflammatory response in critically ill patients with and without acute renal failure (ARF).

Patients and method: Twenty-five critically ill patients, from general and cardiac intensive care units (ICUs) in a university hospital, were studied. Eight had ARF and 17 had normal or mildly impaired renal function. The comparator group included 82 nonhospitalized patients with normal renal function and varying haemoglobin concentrations. In the patients, levels of haemoglobin, serum EPO, C-reactive protein, IL-1beta, IL-6, serum iron, ferritin, vitamin B12 and folate were measured, and Coombs test was performed from ICU admission until discharge or death. Concurrent EPO and haemoglobin levels were measured in the comparator group.

Results: EPO levels were initially high in patients with ARF, falling to normal or low levels by day 3. Thereafter, almost all ICU patients demonstrated normal or low EPO levels despite progressive anaemia. IL-6 exhibited a similar initial pattern, but levels remained elevated during the chronic phase of critical illness. IL-1beta was undetectable. Critically ill patients could not be distinguished from nonhospitalized anaemic patients on the basis of EPO levels.

Conclusion: EPO levels are markedly elevated in the initial phase of critical illness with ARF. In the chronic phase of critical illness, EPO levels are the same for patients with and those without ARF, and cannot be distinguished from noncritically ill patients with varying haemoglobin concentrations. Exogenous EPO therapy is unlikely to be effective in the first few days of critical illness.

Figure 1

Box and whisker plot of erythropoietin (EPO) concentrations against time for all patients. Hollow circles indicate outliers (cases with values of the variable between 1.5 and 3 times the length of the corresponding box for that day and group); filled circles indicate extreme values (cases with values greater than 3 times the corresponding box for that day and group). ARF, acute renal failure.

Figure 2

Box and whisker plot of haemoglobin concentrations against time for all patients. Hollow circles indicate outliers (cases with values of the variable between 1.5 and 3 times the length of the corresponding box for that day and group); filled circles indicate extreme values (cases with values greater than 3 times the corresponding box for that day and group). ARF, acute renal failure.

Figure 3

Box and whisker plot of IL-6 concentrations against time for all patients. Hollow circles indicate outliers (cases with values of the variable between 1.5 and 3 times the length of the corresponding box for that day and group); filled circles indicate extreme values (cases with values greater than 3 times the corresponding box for that day and group). ARF, acute renal failure.

Figure 4

Analysis of median levels of erythropoietin (EPO) and haemoglobin (Hb) for cases (using all data from each patient), compared with comparator group subjects (single data values). (Comparator group subjects are referred to as 'controls'.) ARF, acute renal failure.