Maintenance of effective renal function during hibernation and arousal from torpor

The kidneys of hibernating mammals shut down during bouts of torpor, when blood pressure decreases to levels insufficient for maintenance of kidney filtration. As a consequence, the kidneys lose the cortico-papillary osmotic gradients necessary for concentrating urine. Yet these animals need to regain kidney function within a time period of several hours during their weekly arousal bouts. To achieve this goal, hibernators must carefully orchestrate perfusion of the kidney such that blood homeostasis is maintained while simultaneously protecting renal cells from rapid changes in extracellular osmolality and urea concentration. My research has found that arousing prairie dogs orchestrate this suite of events by dissociating kidney perfusion and filtration from blood pressure during the early stages of arousal. This occurs as a result of elevated vasoconstrictors and altered sensitivity of the renal artery to these vasoconstrictors such that glomerular filtration resumes at a body temperature of 26.5°C. This delay is important so that cortico-papillary gradients have sufficient time to return before filtration resumes. To enhance the speed at which the cortico-papillary gradients return, I also found that arousing prairie dogs recruit distinct nephron populations differentially to ensure an expeditious return of this gradient and the subsequent ability to concentrate urine. But this rapid return poses a particular challenge to renal cells: a drastic change in extracellular osmolality and urea concentration. This challenge is dealt with by relying on intracellular heat shock proteins (HSP's) and a switch to protective organic osmolytes that can be accumulated more readily through cellular uptake as opposed to de novo synthesis. In sum, prairie dogs precisely match the levels of protective osmolytes to extracellular salt and urea concentrations at all stages of arousal. Despite a return of filtration during arousal, overall kidney perfusion and filtration never return to euthermic levels during arousal. This depression, coupled with extensive periods of immobility, should predispose prairie dogs to bone loss and calcium-based kidney stone formation. However, prairie dogs accumulate significant bone mineral density in the period leading up to hibernation with a concomitant decrease in plasma calcium. Bone mineral density is then maintained during hibernation while plasma calcium remains depressed. A side effect of this result is that filtered calcium loads decrease and at the end of a hibernation season prairie dogs have very few calcium deposits within the kidney. The conditions encountered by hibernating animals are analogous to those faced by chronic and acute renal failure patients, in addition to humans confined to bed rest or long-distance space travel. This dissertation research illuminates the strategies that hibernating animals employ to survive analogous conditions and may offer insight to developing novel treatment strategies for these pathologies.