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Is oxidative stress differentially regulated in the renal cortex and medulla?

Nature Clinical Practice Nephrology volume 2, pages 118–119 (2006)Cite this article

In biological systems, one-electron and two-electron reductions of oxygen (O2) generate reactive oxygen species (ROS) including superoxide (O2−•), hydrogen peroxide (H2O2), hypochlorous acid and hydroxyl radicals. To lessen the potentially injurious effects of these ROS, superoxide dismutase (SOD) and catalases have evolved to remove O2−• and H2O2, respectively, within eukaryotic cells. This story becomes more complex, however, as O2−• is also produced by NADPH oxidases for use in intracellular signaling and in bacterial killing by leukocytes. Furthermore, in the kidney and elsewhere, ROS control transport across epithelia and modulate microvascular reactivity.

Renal O2 consumption is largely dedicated to reclamation of sodium (Na+) from glomerular filtrate. Loosely speaking, the kidney is a multistage processor that performs the majority of Na+ reabsorption in the cortex, with delicate adjustment of the final urine Na+ content in the medulla. The tubular–vascular relationships in these regions are tailored to their respective tasks. In the cortex, a dense capillary plexus reabsorbs filtrate reclaimed by the proximal nephron. In the medulla, the counterflow arrangement of microvessels and nephrons accomplishes urinary concentration. As a consequence of medullary countercurrent exchange, shunting of O2 from the descending vasa recta causes low O2 tension (pO2). The hypothesis that the medulla exists at the brink of hypoxic injury is supported by both natural and laboratory observations. Early in the life of humans with sickle cell anemia, hypoxic sickling induces papillary necrosis and loss of urine concentrating capacity. Experimental hypoxic insults to the kidney tend to injure the thick ascending limb of Henle, the medullary nephron segment that most avidly consumes O2.1

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Acknowledgements

Studies in our laboratory have been supported by NIH grants DK42495, DK68492, DK67621, HL68686 and HL78870.

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  1. Professor of Medicine at the University of Maryland, Baltimore, MD, USA

    Thomas L Pallone

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Correspondence to Thomas L Pallone.

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Pallone, T. Is oxidative stress differentially regulated in the renal cortex and medulla?. Nat Rev Nephrol 2, 118–119 (2006). https://doi.org/10.1038/ncpneph0083

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