Take My Breath Away: Hypoxia and the Kidney #xBio

Apr 27 2014 Published by under EB2014

Fredrik Palm220

Nils Axel Fredrik Palm

On Sunday, April 27, Fredrik Palm, PhD, will be honored with the APS Renal Section Young Investigator Award Lecture, Cause and Consequence of Intrarenal Tissue Hypoxia.

Dr. Palm has searched for the cause and significance of diabetic renal hypoxia (sometimes called pseudohypoxia) and the role of mitochondrial dysfunction in this pathology. He is currently a Professor in Experimental Renal Medicine at Linkoping University in Sweden, with a lab at Uppsala University as well. He also continues to have an adjunct appointment at Georgetown University where he did postdoctoral studies and had his first faculty appointments.

In case you don’t catch his Sunday morning lecture (10:30 in room 27 of the convention center), notes will be posted from it shortly afterwards. Check back later, but don’t hold your breath!

 Lecture Notes

Studies in patients with hypoxia from living at high altitude or sleep show that these reductions in O2 tension can produce chronic kidney disease (CKD) or accelerate a preexisting renal condition. Since blood flow to the kidney is not under humoral control, oxygen consumption by the kidney is often the driving force in early disease (leading some investigators to refer to this condition as pseudohypoxia).

From Clin Exp Pharmacol Physiol. 2013 Feb;40(2):123-37. doi: 10.1111/1440-1681.12034.

From Clin Exp Pharmacol Physiol. 2013 Feb;40(2):123-37. doi: 10.1111/1440-1681.12034.

Obviously, oxygen is vital to life. There are multiple levels of entry into the tissue hypoxia schema proposed by Dr. Palm (see figure; it's complex). His work focuses on mitochondrial O2 consumption driven by oxidative stress and uncoupling of ATP production. Oxidative stress stimulates production of uncoupling protein which results in "waste" of oxygen without corresponding energy storage in the mitochondria.

Mice that lack uncoupling protein, when made diabetic, do not get evidence of kidney damage such as proteinuria. These observations are not specific for diabetes; virtually all progressive kidney diseases are states of oxidative stress and uncoupling.

Even in the absence of oxidative stress, hypoxia at the tissue level can induce proteinuria and scarring. For example, chronic treatment with thyroid hormone can elevate oxygen consumption and produce or accelerate kidney damage.

Of course, the kidney does have some defense systems built in for hypoxic occasions. Hypoxia-inducible factors (HIF) are proteins induces by low oxygen (duh). Upregulation of HIF can protect diabetic animals from kidney damage by preventing downstream effects of hypoxia.

Dr. Palm presented an incredible collection of data to support the central role of tissue hypoxia in the pathogenesis of kidney disease, especially diabetes, and the progression of CKD. Congratulations!

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