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Kidney Week

Abstract: PO0402

Probiotics Supplementation Protects the Transition from AKI to CKD in Aged Mice via the Kidney-Gut Axis

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kim, Myung-Gyu, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Fang, Yina, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Yoon Sook, Ko, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Hee Young, Lee, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Yang, Jihyun, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Oh, Sewon, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Jo, Sang-Kyung, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Cho, Won-Yong, Korea University Anam Hospital, Seoul, Korea (the Republic of)
Background

Several epidemiological studies have reported that acute kidney injury (AKI) is more frequent in the elderly and they often progress to chronic kidney disease (CKD). Chronic inflammation has recently been reported as an important mechanism mediating CKD progression after AKI in the elderly. This study investigated how kidney and intestinal crosstalk is involved in exacerbation of inflammation in AKI and whether microbial targeted therapy could modulate the transition from AKI to CKD in aged mice.

Methods

In young and aged C57BL/6 mice, 25min bilateral ischemia reperfusion injury (IRI) was applied, and then colon inflammation, histological changes and intestinal barrier integrity were compared for 28 days post-IRI. To determine the role of the microbiome on kidney-gut crosstalk, we analyzed microbiome from feces in young and aged mice and examined the effects of probiotics supplementation.

Results

M1 predominant inflammation was observed in the kidneys of aged mice compared to young mice for 28 days after IRI. Interestingly, this intrarenal inflammatory milieu in aged mice was similarly observed in the colon on day3 post IRI. The increased inflammatory cytokines in the colon were accompanied by an increase in TUNEL-positive apoptotic colon epithelial cells, resulting in increased intestinal permeability in aged mice for 28 days. The AKI-induced “leaky gut” also showed a strong positive correlation with high TNF-α expression in mesenteric lymph nodes. Microbiome analysis revealed changes in Lactobacillus and Bifidobacterium in aged mice at the genus level. To clarify the role of the microbiota, probiotics were administered for 2 months during the AKI recovery period. We observed that administration of Bifidobacterium (B. longum + B. bifidum) altered intestinal Th17/Treg balance and improved kidney inflammation, but not intestinal leakage. They finally resulted in improvements in GFR and kidney fibrosis, suggesting that kidney-gut crosstalk in aged mice makes an important contribution to AKI to CKD transition.

Conclusion

Our study suggests that exacerbation of chronic inflammation through the kidney-gut axis is an important mediating mechanism of the transition from AKI to CKD in the elderly. Therefore, strategies to modulate the microbiota are considered promising to improve outcomes in elderly AKI.

Funding

  • Government Support – Non-U.S.