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Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans

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Abstract

Purpose

Erythropoietin (EPO) is mainly synthesized within renal peritubular fibroblasts, and also other tissues such as the liver possess the ability. However, to what extent non-kidney produced EPO contributes to the hypoxia-induced increase in circulating EPO in adult humans remains unclear.

Methods

We aimed to quantify this by assessing the distribution of EPO glycoforms which are characterized by posttranslational glycosylation patterns specific to the synthesizing cell. The analysis was performed on samples obtained in seven healthy volunteers before, during and after 1 month of sojourn at 3,454 m altitude.

Results

Umbilical cord (UC) plasma served as control. As expected a peak (p < 0.05) in urine (2.3 ± 0.5-fold) and plasma (3.3 ± 0.5-fold) EPO was observed on day 1 of high-altitude exposure, and thereafter the concentration decreased for the urine sample obtained after 26 days at altitude, but remained elevated (p < 0.05) by 1.5 ± 0.2-fold above the initial sea level value for the plasma sample. The EPO glycoform heterogeneity, in the urine samples collected at altitude, did not differ from values at sea level, but were markedly lower (p < 0.05) than the mean percent migrated isoform (PMI) for the umbilical cord samples.

Conclusion

Our studies demonstrate (1) UC samples express a different glycoform distribution as compared to adult humans and hence illustrates the ability to synthesis EPO in non-kidney cells during fetal development (2) as expected hypoxia augments circulating EPO in adults and the predominant source here for remains being kidney derived.

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Abbreviations

EPO:

Erythropoietin

Glc-NAc:

N-acetylglucosamine

HA:

High altitude

MAIIA:

Membrane-assisted isoform immunoassay

PMI:

Percent migrated isoform

SL:

Sea level

WGA:

Wheat germ agglutinin

UC:

Umbilical cord

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Conflict of interest

The authors declare not to have any conflict of interest with regard to the study.

Author information

Authors and Affiliations

  1. Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Winterthurerstrasse 190, 8057, Zürich, Switzerland

    Anne-Kristine Meinild Lundby, Stefanie Keiser, Christoph Siebenmann & Carsten Lundby

  2. Department of Obstetrics, University Hospital Zürich, Zürich, Switzerland

    Leonhard Schäffer

  3. Food and Nutrition and Sport Science, Gothenburg University, Gothenburg, Sweden

    Carsten Lundby

Authors
  1. Anne-Kristine Meinild Lundby
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  2. Stefanie Keiser
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  3. Christoph Siebenmann
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  4. Leonhard Schäffer
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  5. Carsten Lundby
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Corresponding author

Correspondence to Carsten Lundby.

Additional information

Communicated by Guido Ferretti.

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Lundby, AK.M., Keiser, S., Siebenmann, C. et al. Kidney-synthesized erythropoietin is the main source for the hypoxia-induced increase in plasma erythropoietin in adult humans. Eur J Appl Physiol 114, 1107–1111 (2014). https://doi.org/10.1007/s00421-014-2844-7

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  • DOI: https://doi.org/10.1007/s00421-014-2844-7

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