The oxygen cascade in hemodialysis patients and native high altitude dwellers- lessons from extreme physiology to benefit patients with end-stage renal disease

Kooman, J. P., Stenvinkel, P., Shiels, P. G. , Feelisch, M., Canaud, B. and Kotanko, P. (2021) The oxygen cascade in hemodialysis patients and native high altitude dwellers- lessons from extreme physiology to benefit patients with end-stage renal disease. American Journal of Physiology: Renal Physiology, 320(3), F249-F261. (doi: 10.1152/ajprenal.00540.2020) (PMID:33356957)

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Abstract

Hemodialysis patients repeatedly undergo intradialytic low arterial oxygen saturation, as well as low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. Dialysis treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, capillary rarefaction and reduced mitochondrial efficacy can further affect the balance between cellular oxygen supply and demand. Whereas it has been convincingly demonstrated that a reduced perfusion of heart and brain during dialysis contributes to organ damage, the significance of systemic hypoxia remains uncertain, although it may contribute to oxidative stress, systemic inflammation and accelerated senescence. These abnormalities along the oxygen cascade of dialysis patients appear to be diametrically opposite to the situation in Tibetan highlanders and Sherpa, whose physiology adapted to the inescapable hypobaric hypoxia of their living environment over many generations. Their adaptation includes pulmonary, vascular and metabolic alterations with enhanced capillary density, nitric oxide production and mitochondrial efficacy without oxidative stress. Improving the tissue oxygen supply in dialysis patients depends primarily on preventing hemodynamic instability by increasing dialysis time/frequency or prescribing cool dialysis. Whether dietary or pharmacological interventions, such as the administration of L-arginine, fermented food, nitrate, Nrf2 agonists or prolyl hydroxylase 2 inhibitors improve clinical outcome in dialysis patients warrants future research.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Shiels, Professor Paul
Authors: Kooman, J. P., Stenvinkel, P., Shiels, P. G., Feelisch, M., Canaud, B., and Kotanko, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:American Journal of Physiology: Renal Physiology
Publisher:American Physiological Society
ISSN:1931-857X
ISSN (Online):1522-1466
Published Online:28 December 2020
Copyright Holders:Copyright © 2020 American Journal of Physiology-Renal Physiology
First Published:First published in American Journal of Physiology: Renal Physiology 320(3): F249-F261
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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