Abstract: FR-PO121

Raised Serum Creatinine and Decrease in Renal Cyp2c11 Gene Expression in Bile Duct Ligated Rats Is Attenuated by the Adsorbent of Gut Bio-Toxins: YAQ001

Session Information

Category: Acute Kidney Injury

  • 003 AKI: Clinical and Translational

Authors

  • Oomatia, Amin, University College London, London, United Kingdom
  • Chiara, Francesco, University College London, London, United Kingdom
  • Macnaughtan, Jane, University College London, London, United Kingdom
  • Jalan, Rajiv, University College London, London, United Kingdom
Background

Renal dysfunction confers a poor prognosis in patients suffering from acute-on-chronic liver failure. Bile duct ligation (BDL), an established model for cholestatic liver injury, potentiates LPS mediated acute kidney injury (AKI) in rats. Gut decontamination using antibiotics attenuates this, suggesting translocation of gut flora products in cirrhosis may prime the kidney for exaggerated inflammatory responses. Yaq001 (YQ) is a non-absorbable, ingested carbon polymer, which adsorbs and reduces translocation of biotoxins. We investigated the effect it has on BDL rats.

Methods

Sprague-Dawley rats underwent either BDL or sham laparotomy and were then randomised to normal or YQ supplemented chow for 2-weeks. At four weeks, LPS or saline was injected intraperitoneally. Rats were sacrificed two hours later. Serum and tissue were collected. Next generation sequencing of RNA expression in rat kidney (sham vs BDL vs BDL+YQ, n=2 vs 3 vs 3) was performed for 17,327 and then analysed using DESeq2 workflow.

Results

Serum creatinine (SC) of groups of interest are shown in table 1. A difference in SC in BDL+LPS+YQ vs BDL+LPS rats was seen (32vs41 µmol/L), and tended towards statistical significance (p=0.086). Differential gene expression was significant (q<0.05) for a 107 genes in the BDL vs Sham groups, and 886 in the BDL vs BDL+YQ groups. Shrunken log2 fold change of expression for Cyp2c11, a CYP450 enzyme, was decreased in Sham vs BDL (8.66 vs 6.64, q=0), only to return to normal levels with treatment Yaq001 (5.87 vs 8.11, q=0.001).

Conclusion

BDL predisposes rats to AKI when faced with a septic insult, which is attenuated by Yaq001. Decrease in Cyp2c11 expression in BDL animals, which is normalised by Yaq001, suggests that disruption of cellular responses to oxidative stress may account for why kidneys in BDL rats and possibly cirrhotic patients are more susceptible to septic injury. Further research is needed to determine the effects of Cyp2C11 dysregulation and its effects on kidneys in cirrhosis.

Table 1
 ShamBDLBDL+YQSham+LPSBDL+LPSBDL+LPS
+YQ
(n)2229278128
Median SC
(µmol/L)
28.1323124.54132
Range
(µmol/L)
21.2-3923-4018.8-44.219.8-32.622.4-6025.3-38
 p=0.024 p=0.004 

Funding

  • Commercial Support