Renal oxygenation: From data to insight

Abstract

Computational models have made a major contribution to the field of physiology. As the complexity of our understanding of biological systems expands, the need for computational methods only increases. But collaboration between experimental physiologists and computational modellers (ie theoretical physiologists) is not easy. One of the major challenges is to break down the barriers created by differences in vocabulary and approach between the two disciplines. In this review, we have two major aims. Firstly, we wish to contribute to the effort to break down these barriers and so encourage more interdisciplinary collaboration. So, we begin with a “primer” on the ways in which computational models can help us understand physiology and pathophysiology. Second, we aim to provide an update of recent efforts in one specific area of physiology, renal oxygenation. This work is shedding new light on the causes and consequences of renal hypoxia. But as importantly, computational modelling is providing direction for experimental physiologists working in the field of renal oxygenation by: (a) generating new hypotheses that can be tested in experimental studies, (b) allowing experiments that are technically unfeasible to be simulated in silico, or variables that cannot be measured experimentally to be estimated, and (c) providing a means by which the quality of experimental data can be assessed. Critically, based on our experience, we strongly believe that experimental and theoretical physiology should not be seen as separate exercises. Rather, they should be integrated to permit an iterative process between modelling and experimentation.

Influence of blood haemoglobin concentration on renal haemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep

“…The mechanisms underlying these phenomena remain unknown. However, arterial‐to‐venous (and in the medulla descending to ascending vasa recta) oxygen shunting 12,39 and increased heterogeneity of tissue perfusion 40 and thus oxygenation 41 could potentially lead to less efficient oxygen transport to tissue. Regardless, our current findings show that, during experimental CPB in sheep, renal venous blood PO 2 can be increased by increasing blood [Hb] without appreciable changes in cortical or medullary tissue PO 2 .…”

“…Experimental models of CPB in rats, 7 pigs, 8 and sheep 5,6 are all associated with renal medullary tissue hypoxia. Computational models of renal oxygenation also predict medullary hypoxia during CPB 9‐12 . Furthermore, risk of AKI is associated with indices of intra‐operative renal hypoxia, as assessed by urinary oxygen tension (PO 2 ) 13‐15 or near infrared spectroscopy 16,17 .…”

Renal microvascular oxygen tension during hyperoxia and acute hemodilution assessed by phosphorescence quenching and excitation with blue and red light

“…8,9 As such, oxygen is not impacted by anatomical divisions within organs; it does not differentiate between renal cortex or medulla, other than by local aspects of metabolic supply (perfusion) and demand (cellular metabolic requirement) and by vascular anatomy. [10][11][12] The anatomy and physiology of the kidney reflect its multiple functions including waste removal, fluid and electrolyte homeostasis, and erythrogenesis. To perform these functions, the kidney receives 25% of the cardiac output and consumes about 20% of global oxygen delivery.…”

How to increase cellular oxygen availability in COVID‐19?

“…As various diseases are associated with hypoxia, 12 , 13 , 14 , 15 it could be beneficial to modify the baseline Hb‐O 2 affinity. As mentioned above, the Hb‐O 2 affinity can be modulated through various endogenous effectors.…”