Keynote Message

Chronic kidney disease (CKD) is a common naturally occurring medical condition in elderly cats, yet an etiology for this disease process has not been elucidated. Human CKD is associated with progressive loss of renal parenchyma and function with age. Renal aging also involves loss of an appropriate response toward injury, as seen in aging human populations where kidney injury is more common, clinically more severe, and kidney function is less likely to recover. Whether feline CKD results from similar aging processes that predispose the organ to failure, or if other factors are involved remains to be determined. Telomeres are protective structures that serve to cap chromosome ends and so are critical for maintaining genome stability. When telomeres reach a critically shortened state they are no longer able to effectively cap the end of the chromosome, and so they themselves are detected as DNA damage and trigger a response resulting in permanent cell cycle arrest known as cellular senescence. Senescence can also occur via non-telomere-dependent pathways. Associations between oxidative stress, telomere shortening, senescence, and inflammation have been suggested. Thus, the investigation of these processes is particularly pertinent for feline CKD, as it is a disease characterized by tubulointerstitial inflammation, and decreased antioxidant defense mechanisms and increased oxidative stress have been documented in these patients. This session will discuss the pathophysiology of these processes as well as recent work demonstrating associations between telomere shortening, cellular senescence and feline CKD, which serve to further our understanding of renal aging and disease, and have the potential to present novel treatment strategies.

Key References

1.  Quimby JM, Maranon DG, Battaglia CL, McLeland SM, Brock WT, Bailey SM. Feline chronic kidney disease is associated with shortened telomeres and increased cellular senescence. Am J Physiol Renal Physiol. 2013;305(3):F295–303. doi: 10.1152/ajprenal.00527.2012.
http://ajprenal.physiology.org/content/305/3/F295.long

2.  Schmitt R, Melk A. New insights on molecular mechanisms of renal aging. Am J Transplant. 2012;12(11):2892–900. doi: 10.1111/j.1600-6143.2012.04214.x
http://onlinelibrary.wiley.com/doi/10.1111/j.1600-6143.2012.04214.x/abstract

3.  Schmitt R, Cantley LG. The impact of aging on kidney repair. Am J Physiol Renal Physiol. 2008;294(6):F1265–72. doi: 10.1152/ajprenal.00543.2007
http://ajprenal.physiology.org/content/294/6/F1265.long

4.  Melk A, Ramassar V, Helms LM, Moore R, Rayner D, Solez K, Halloran PF. Telomere shortening in kidneys with age. J Am Soc Nephrol. 2000;11(3):444–53
http://jasn.asnjournals.org/content/11/3/444.long