Enhanced sensitivity to ischemia reperfusion injury in a mouse model of accelerated aging is associated with blunted upregulation of urine KIM1

Autor: Helen Goodluck, Natalia Lopez, Yuji Oe, Sadhana Kanoo, Young Chul Kim, Pamela Maher, Volker Vallon
Rok vydání: 2023
Předmět:
Zdroj: Physiology. 38
ISSN: 1548-9221
1548-9213
DOI: 10.1152/physiol.2023.38.s1.5733840
Popis: Objective: Advanced age enhances the risk of acute kidney injury (AKI) but the mechanisms remain unclear. Kidney injury molecule 1 (KIM1) is a sensitive measure of tubular injury (PMC2915578) but also confers a phagocytic phenotype on epithelial cells important for kidney recovery (PMC2293335), and a higher KIM1/serum creatinine (SCr) ratio was associated with better kidney recover over 6 months (PMID31646460). Here we compared the response to kidney ischemia reperfusion injury (IR) in regular C57BL6 mice with a mouse strain of accelerated aging (Senescence Accelerated Mouse-Prone 8, SAMP8). Methods: Bilateral renal artery clamping for 15 or 25 minutes (15IR, 25IR) or sham operation was performed under ketamine-xylazine anesthesia and temperature-controlled conditions (36-37°C) in 3 months old male C57BL6 and SAMP8 mice (n=6-8 mice/group). Results: In response to 25IR, none of the SAMP8 mice survived beyond day 5, while 87% of C57BL6 mice survived for 24 days (end of study) together with all 15IR and sham mice. In response to 15IR, the rise in plasma creatinine on day 1 was significantly greater in SAMP8 vs C57BL6, associated with greater urine NGAL/creatinine ratios but a blunted rise in urine KIM1/creatinine. The same phenotype was observed on day 1 in 25IR, except that the rise in urine NGAL/creatinine was likewise blunted in SAMP8. In a second set of mice we compared 15IR in SAMP8 with 25IR in C57BL6 to induce similar kidney injury in both strains as indicated by a similar rise in plasma creatinine and urine NGAL/creatinine on day 1. Also under these conditions, the increase in urine KIM1/creatinine observed in C57BL6 was absent in SAMP8. Conclusions: Mice with accelerated aging show an increased sensitivity to renal ischemia reperfusion injury. This was associated with, and potentially in part due to, blunted KIM1 expression, cleavage and/or function. Supported by National Institutes of Health (NIH) Grants RF1AG061296 (PM, VV), R01DK132690 (VV), and P30 DK079337 (VV), the Department of Veterans Affairs, and a fellowship of the Manpei Suzuki Diabetes Foundation (YO). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Databáze: OpenAIRE
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