Hyperglycaemia emerging during general anaesthesia induces rat acute kidney injury via impaired microcirculation, augmented apoptosis and inhibited cell proliferation

Shai Efrati*, Sylvia Berman, Ramzia Abu Hamad, Yariv Siman-Tov, Michael Chanimov, Joshua Weissgarten

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Aim: Major surgery under general anaesthesia frequently triggers acute kidney injury by yet unknown mechanisms. We investigated the role of anaesthesia-triggered systemic hyperglycaemia in impairment of renal functioning, renal tissue injury, intra-renal Angiotensin-II synthesis and endogenous insulin production in anaesthetized rats. Methods: Eighty-eight Sprague-Dawley rats underwent general anaesthesia for 1 h by different anaesthetic compounds. Some of the animals were either injected with high glucose, or received insulin prior to anaesthesia. Blood pressure, renal functioning estimated by cystatin-C and urea, renal perfusion evaluated by laser Doppler technique, blood glucose and insulin were surveyed. Subsequently, rat kidneys were excised, to be used for immunohistochemical examinations or preparation of renal extracts for intra-renal Angiotensin-II measurements. Results: Elevated blood sugar was observed 5 min following induction of anaesthesia, concurrently with deterioration of renal functioning, drop of systemic blood pressure and decreased renal blood flow. Blood insulin concentrations positively correlated with glucose levels. Intra-renal Angiotensin-II was significantly augmented. Immunohistochemical examinations demonstrated enhanced staining for pro-apoptotic proteins and negligible cell proliferation in tubular tissues. Renal damage resultant from anaesthesia-induced hyperglycaemia could be attenuated by insulin injections. Rats challenged with glucose prior to anaesthesia demonstrated cumulative hyperglycaemia, further increase in insulin secretion, drop of renal blood flow and increased apoptosis. The effects were specific, since they could not be mimicked by replacing glucose with mannose. Conclusion: Anaesthesia-induced hyperglycaemia affects intra-renal auto-regulation via decreased renal perfusion, thus triggering renal function deterioration and tubular injury. Increased intra-renal Angiotensin-II aggravates the damage. Tight hypoglycaemic control might prevent or, at least, attenuate anaesthesia-induced renal injury. This experimental study investigated the role of hyperglycaemia emerging during general anaesthesia in induction of acute kidney injury (AKI). Hyperglycaemia may increase the risk of AKI by disturbing intra-renal autoregulation, increasing intra-renal Angiotensin-II and augmenting renal cell apoptosis.

Original languageEnglish
Pages (from-to)111-122
Number of pages12
JournalNephrology
Volume17
Issue number2
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

  • acute kidney injury
  • anaesthesia
  • hyperglycaemia
  • renal auto-regulation

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