Acute bile duct ligation ameliorates ischemic renal failure

Nephron Physiol. 2003;95(2):p28-35. doi: 10.1159/000073677.

Abstract

Background: Biliary obstruction affects the renal response to ischemia and also elicits a hepatic cytokine response. Using a murine model, we now test the hypothesis that these hepatic cytokines help determine the outcome of ischemic acute renal failure.

Methods: C3H/HEN mice were subjected to bile duct ligation 24 h (ABDL) or 7 days (CBDL) prior to induction of acute ischemic renal failure (ARF). Serum creatinine (Scr), cytokine mRNA abundance, and renal histology were studied 24 h after renal ischemia.

Results: ABDL prior to ARF resulted in amelioration of renal injury (Scr 0.7 +/- 0.1 mg/dl compared to 2.5 +/- 0.1 mg/dl in sham/ARF group, (mean +/- SE, n = 11/group). CBDL exacerbated renal injury. Increased hepatic mRNA for interleukin-10 (IL10) and interleukin-1 receptor antagonist (IL1RA) was detected in the ABDL/ARF group but not in the CBDL/ARF group. These data suggest that hepatic production of IL10 and IL1RA in response to ABDL ameliorates ischemic ARF, an effect that is lost after several days of BDL.

Conclusion: Our data support the concept that hepatic cytokines modulate renal injury. This adds a new dimension in our understanding of renal injury in the setting of hepatic disease.

MeSH terms

  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Cholestasis / physiopathology
  • Common Bile Duct / physiopathology
  • Common Bile Duct / surgery*
  • Creatinine / blood
  • Disease Models, Animal
  • Ischemia / blood
  • Ischemia / complications*
  • Ischemia / physiopathology
  • Kidney / blood supply*
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / prevention & control*
  • Ligation
  • Liver / chemistry
  • Liver / physiopathology
  • Male
  • Mice
  • Mice, Inbred C3H
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / antagonists & inhibitors
  • Receptors, Interleukin / metabolism
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / metabolism
  • Receptors, Interleukin-10

Substances

  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Receptors, Interleukin-10
  • Creatinine