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Kidney Week

Abstract: TH-PO122

Selective Decontamination of Digestive Tract Attenuates Kidney Ischemia/Reperfusion Injury and Distant Organ Damage via Immune Modulatory Effect

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Yang, Jihyun, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Jo, Sang-Kyung, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Oh, Sewon, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Lee, Junyong, Korea University Anam Hospital, Seoul, Korea (the Republic of)
  • Kim, Myung-Gyu, Korea University Anam Hospital, Seoul, Korea (the Republic of)
Background

Emerging evidence suggests the critical role of gut as an amplifier of systemic inflammation in diverse pathological conditions. Selective decontamination of digestive tract (SDD) is known to inhibit colonization by aerobic gram-negative bacilli while preserving anaerobic microflora and is currently being used to prevent infection and also to reduce mortality in critically ill patients. We aimed this study to examine the effect of SDD on the severity of kidney injury as well as on distant organ damage and also the underlying mechanisms.

Methods

We used male C57L/B6 mouse bilateral ischemia/reperfusion injury(IRI) after SDD, which was the mixture of three antibiotics (neomycin 25mg/kg, ampicillin 60mg/kg, and metronidazole 25mg/kg) given by orogastric gavage once daily for 12 days. The renal function, colon immunity, local and systemic inflammation level was assessed. We measured liver function test to check distant organ injury.

Results

Kidney IRI but not bilateral nephrectomy provoked increased intestinal permeability. The “leaky gut” following IRI was accompanied by increased colon apoptosis, decreased claudin-1 expression. Ly6G+ neutrophil infiltration and M1proinflammatory macrophages increased in colon after kidney IRI. SDD before IRI but not bilateral nephrectomy resulted in significant attenuation of kidney injury and inflammation as well as distant organ injury. The protective effect of SDD was associated with better preservation of intestinal permeability, reduced colon apoptosis and restored claudin-1 expression. SDD also led to the expansion of M2 anti-inflammatory macrophages and Tregs in colon. Spleen Tregs and Foxp3 expression were also increased in SDD mice. Mesenteric lymph node cells from SDD mice showed reduced proliferative response upon TCR stimulation, suggesting the state of immune tolerance compared to control mice.

Conclusion

Our results showed the critical role of intestine as an amplifier of kidney injury, inflammation and distant organ damage after IRI. We also showed the protective effect of SDD might be partially mediated by immune modulatory effect through expansion of M2 macrophages and Tregs. Strategies aimed at restoring intestinal integrity, microbiome and intestinal mucosal tolerance could be novel therapeutics in acute kidney injury.