Erythropoietin in the General Population: Reference Ranges and Clinical, Biochemical and Genetic Correlates

Hemoglobin levels are believed to be regulated as per a set point model of regulation. This model of regulation, by which specific levels of a parameter are targeted and defended by physiological systems, implies a particular population correlation between the parameter and its controlling hormone. Empirical population correlations of other parameters and their controlling hormones, have denied the presence of such set point‐based regulation. To assess if hemoglobin is regulated according to a set point model we performed a systematic search of PubMed/ MEDLINE and Web of Science identifying relevant reports published up to November 2018. Population hemoglobin/erythropoietin level correlations were retrieved, and these empirically derived correlations were compared with the positive correlation implied by a set point model of regulation. Authors of papers containing potentially suitable data were contacted with requests for further analyses, and a meta‐analysis was performed. Twelve correlations between hemoglobin and erythropoietin levels from eleven papers were analyzed. None of these correlations were significantly positive, three, restricted to the normal range of hemoglobin, were significantly negative. All but one of the other correlations showed a negative trend. New analyses of previously published data sets resulted in similar findings. In particular a new analysis of large data sets of males ( n = 2417) and females ( n = 2592) with normal range hemoglobin levels, revealed significantly negative correlations. A meta‐analysis of our results indicated that the data overall are not consistent with a positive relationship between hemoglobin and erythropoietin ( P < 0.0001). Population data indicate that individuals do not have set point levels of hemoglobin.

show abstract

“…; Artunc and Risler ; Grote Beverborg et al. ).We did not include two further studies (Malagarnera et al. ; Panjeta et al.…”

Section: Resultsmentioning

confidence: 99%

Population data provide evidence against the presence of a set point for hemoglobin levels or tissue oxygen delivery

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…In particular, the association was independent of systolic blood pressure, the inflammation marker hs‐CRP, haemoglobin, and renal function. We recently showed a strong association between EPO levels and the components of the metabolic syndrome such as waist circumference, serum glucose, and blood pressure, which are important cardiovascular risk factors . However, EPO levels were associated with new‐onset HF independent of these variables.…”

Section: Discussionmentioning

confidence: 99%

High serum erythropoietin levels are related to heart failure development in subjects from the general population with albuminuria: data from PREVEND

Beverborg

Wal

Klip

et al. 2016

European J of Heart Fail

Self Cite

View full text Add to dashboard Cite

Aims In patients with heart failure (HF), serum erythropoietin (EPO) levels are elevated and associated with disease severity and outcome. Whether endogenous EPO levels are prospectively associated with the development of HF or cardiovascular events in the general population is unknown. Methods and results Serum EPO levels were measured at baseline in 6686 subjects enrolled in the Prevention of REnal and Vascular ENd‐stage Disease (PREVEND) study. Mean age (±SD) was 53 ± 12 years, 49.8% were male, and the median (interquartile range) EPO level was 7.7 (5.9–10.2) IU/L. During a median follow‐up of 8.3 (7.7–8.8) years, 209 (3.1%) subjects were newly diagnosed with HF, 97 (1.5%) died of a cardiovascular cause, and 386 (6.0%) subjects had a non‐fatal cardiovascular event (277 cardiac events and 93 strokes). Each doubling of EPO level was multivariably associated with new‐onset HF [hazard ratio (HR) 1.32, 95% confidence interval (CI) 1.03–1.69, P = 0.031]. EPO levels showed interaction with urinary albumin excretion (P = 0.006) and were only associated with HF in subjects with albuminuria (HR 1.51, 95% CI 1.13–2.03, P = 0.005). There was an independent association of EPO levels with stroke in women (HR 1.82, 95% CI 1.24–2.65, P = 0.002), but not in men. No association was observed for EPO levels with other cardiovascular events or cardiovascular mortality. Conclusion High serum EPO levels are independently associated with an increased risk of new‐onset HF in subjects with albuminuria. More research into the pathophysiological mechanisms linking EPO levels to HF is needed to understand this association.

show abstract

“…Recombinant human erythropoietin (rhuEPO) is given as an adjunct for the therapy of anaemia in individuals affected by many conditions such as chronic kidney disease [2]. In patients with non-uremic anaemia, the EPO levels are several hundred-fold higher [3] (physiological range: 3–18 IU/L [4]). Although rhuEPO administration reduces the number of transfusions in critically ill settings and patients with sepsis, its effect on bacterial growth is unknown.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Recombinant Human Erythropoietin on Bacterial Growth: A Dual-Edged Sword

et al. 2018

View full text Add to dashboard Cite

Background: Hypererythropoietinemia is associated with common diseases like non-uremic anaemia where infection burden is high. Erythropoietin (EPO) is also given as therapy for anaemia associated with chronic kidney disease and cancer and in those who are at a higher risk of infections. EPO is known to have an effect on macrophages by which it helps in the growth of some intracellular pathogens. However, its direct role on bacterial growth is currently unknown. Summary: Here, we investigated the direct effect of recombinant human erythropoietin (rhuEPO) on the growth of pathogenic Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. In silico experiments were designed to gain insight into the mechanisms. We found that 30 IU/L rhuEPO promoted the growth of E. coli and S. aureus and inhibited the growth of P. aeruginosa. In silico observations suggest that bacterial cell surface proteins may interact with the EPO and may cause the observed effects. Key Message: It appears that some pathogens can explore EPO to proliferate and growth of others are inhibited by the same. The consequence of such observation is a matter of widespread concern for future research.

show abstract

Erythropoietin in the General Population: Reference Ranges and Clinical, Biochemical and Genetic Correlates

Cited by 44 publications

References 48 publications

Population data provide evidence against the presence of a set point for hemoglobin levels or tissue oxygen delivery

Population data provide evidence against the presence of a set point for hemoglobin levels or tissue oxygen delivery

High serum erythropoietin levels are related to heart failure development in subjects from the general population with albuminuria: data from PREVEND

The Effect of Recombinant Human Erythropoietin on Bacterial Growth: A Dual-Edged Sword

Contact Info

Product

Resources

About