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Defective renal autoregulation in the chronic bile duct ligation model of liver failure

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Abstract

Background

Cirrhosis of the liver is often associated with an impairment of renal function that is usually not associated with consistent structural abnormalities of the renal parenchyma, but is thought to be the functional consequence of arterial underfilling and reduced arterial blood pressure.

Method

We have used the cirrhosis model of chronic bile duct ligation (BDL) to assess the response of renal blood flow to a change of blood pressure. We have measured renal haemodynamics in BDL rats.

Result

Three weeks after BDL, rats showed elevated levels of total bilirubin, AST, and ALT as well as reduced arterial blood pressure. Creatinine clearance was significantly reduced, and plasma creatinine and urea nitrogen were elevated. Renal blood flow at baseline blood pressure was significantly lower in the BDL group than in the sham group. Clamp-induced reductions of renal perfusion pressure caused significantly greater changes of renal blood flow in BDL than control rats. The autoregulatory index over a comparable blood pressure range averaged 0.28 ± 0.35 in control rats and 1.26 ± 0.6 in BDL rats (p = 0.0004) indicating impairment of renal autoregulation in liver cirrhosis.

Conclusion

Tubuloglomerular feedback (TGF) responses were significantly attenuated in BDL rats, especially in the subnormal flow range. Impairment of renal blood flow autoregulation, to some extent mediated by reduced TGF-mediated vasodilatation, may contribute to the renal vascular constrictor state in liver cirrhosis by preventing the full dilatory response to the blood pressure reduction.

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Authors and Affiliations

  1. Department of Nephrology, NTT East Japan Sapporo Hospital, South 1, West 15, Chuou-ku, Sapporo, 060-0061, Japan

    Tomchika Maoka

  2. Department of Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Tetsuya Kawata, Takao Koike & Toshio Mochizuki

  3. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, 20892, USA

    Jurgen Schnermann

  4. Department of Nephrology, Wakayama Medical University, Wakayama, Japan

    Seiji Hashimoto

Authors
  1. Tomchika Maoka
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  2. Tetsuya Kawata
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  3. Takao Koike
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  4. Toshio Mochizuki
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  5. Jurgen Schnermann
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  6. Seiji Hashimoto
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Corresponding author

Correspondence to Seiji Hashimoto.

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Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

All animal experiments were conducted in accordance with “Hokkaido University Animal Experiment Guidelines”. And all animal experiments were receiving research approval from Hokkaido University animal experiment facility. (2008 − 168).

Informed consent

No relationship. All experiments were done on animals.

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Maoka, T., Kawata, T., Koike, T. et al. Defective renal autoregulation in the chronic bile duct ligation model of liver failure. Clin Exp Nephrol 22, 1052–1060 (2018). https://doi.org/10.1007/s10157-018-1551-9

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  • DOI: https://doi.org/10.1007/s10157-018-1551-9

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