Abstract
The aging kidney is a marked by a number of structural and functional changes, including an increased susceptibility to acute kidney injury (AKI). Previous studies from our laboratory have shown that aging male Fischer 344 rats (24 month) are more susceptible to apoptosis-mediated injury than young counterparts. In the current studies, we examined the initial injury and early recovery phases of mercuric chloride-induced AKI. Interestingly, the aging kidney had decreased serum creatinine compared to young controls 1 day following mercuric chloride injury, but by day 4, serum creatinine was significantly elevated, suggesting that the aging kidney did not recover from injury. This conclusion is supported by the findings that serum creatinine and kidney injury molecule-1 (Kim-1) gene expression remain elevated compared to young controls at 10 days post-injury. To begin to elucidate mechanism(s) underlying dysrepair in the aging kidney, we examined the expression of Twist2, a helix-loop-helix transcription factor that may mediate renal fibrosis. Interestingly, Twist2 gene expression was elevated following injury in both young and aged rats, and Twist2 protein expression is elevated by mercuric chloride in vitro.
Highlights
A number of studies have linked aging with a higher risk for acute kidney injury (AKI) [1,2]
Previous studies from our laboratory have demonstrated that aged male Fischer 344 rats are more susceptible to cisplatin-induced AKI than young counterparts [23], an effect that is linked to an increased susceptibility to apoptosis [23,24]
At day 2 following injury, serum creatinine was elevated in both young (4 month) and aged (20 month) rats, levels were significantly higher in young animals (Figure 1)
Summary
A number of studies have linked aging with a higher risk for acute kidney injury (AKI) [1,2]. Previous studies from our laboratory showed similar results; renal slices from aged Fischer 344 rats fed ad libitum, but not aged caloric-restricted animals which do not develop renal fibrosis and dysfunction [7], were more susceptible to ischemic injury when compared with slices from young animals as assessed by histological and biochemical evaluation [8]. These ex vivo studies demonstrated that the aged proximal tubular epithelial cells had an inherent susceptibility to injury. Mercuric chloride-induced AKI is a relatively pure nephrotoxic model; injury is not responsive to anti-inflammatory treatment [21,22]; this allows the investigation of injury and repair without the important, yet confounding, variable of inflammation-mediated changes
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