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Kidney Week

Abstract: SA-PO727

Impact of Aging on Kidney and Gut Cross-Talk in AKI

Session Information

  • Geriatric Nephrology
    October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Geriatric Nephrology

  • 1100 Geriatric Nephrology

Authors

  • Kim, Myung-Gyu, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
  • Yoon Sook, Ko, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
  • Hee Young, Lee, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
  • Lee, Junyong, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
  • Yang, Jihyun, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
  • Oh, Sewon, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
  • Jo, Sang-Kyung, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea (the Republic of)
Background

Recently, the high incidence of acute kidney damage (AKI) and the mortality rate in elderly population are important healthcare burdens. Although, experimental studies showed that interaction between the kidney and the remote organ (lung, heart, bowel, etc.) could significantly affect the outcome of AKI, the impact of aging on the remote organ effects of AKI are still unknown. Here, we investigated the effects of aging on AKI outcomes, especially kidney and gut crosstalk in animal models.

Methods

In old (10mo) and young (2mo) C57BL/6 mice, 25min bilateral ischemia reperfusion injury (IRI) was applied, and then expression of inflammatory cytokines as well as functional and histological changes of kidney and colon were examined on day 1 and 3 after IRI. Intestinal barrier integrity was assessed by permeability to FITC-dextran.

Results

There was no significant difference in renal function between old and young mice on day1 post IRI, but the mRNA expression of IL-6, TNF-α, IL-12 and IFN-r was significantly higher in the kidneys of old mice than in young mice on day 1, and the expressions of TNF-α and IL-12 were also increased in old mice on day3. The balance of the M1/M2 markers (iNOS/mannose receptor) skewed towards M2 phenotype on day3 post IRI in young mice, however it was significantly blunted in old mice. Interestingly, this intrarenal inflammatory milieu in old mice was similarly observed in the colon. In the aged colon, TNF-α and IL-12 mRNA expression was significantly higher and mannose receptor and arginase-1 expression was lower than in young mice on day3 post IRI. Increased inflammatory cytokines in the colon were accompanied by an increase in TUNEL-positive apoptotic colon epithelial cells and increased permeability of the colon in old mice. The AKI-induced “leaky gut” showed a strong positive correlation with high TNF-α expression in mesenteric lymph nodes, suggesting that persistent inflammation of the kidney after IRI in old mice contributes to increased colon inflammation and permeability.

Conclusion

We conclude that AKI in old mice results in a more M1-related inflammation in the kidney and colon, and worsens AKI-induced “leaky gut”. These results suggest that strategies for targeting intestine might provide novel therapeutic opportunities for reducing poor outcomes in elderly patients with AKI.