Effect of the Surgical Intervention of Laparoscopic Donor Nephrectomy on Proteomic Changes in Living Kidney Donors using either Propofol or Sevoflurane Anaesthesia

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Abstract

Introduction

Surgical intervention i.e. ‘trauma’ induces perioperative stress impacting on systemic inflammatory and humoral responses that are associated with postoperative comorbidity. Different types of anaesthesia and anaesthetic agents are shown to have differential effects on the innate and adaptive immunity. In this study, the biological effect of the surgical intervention combined with propofol or sevoflurane anaesthesia in the healthy cohort of living kidney donors undergoing laparoscopic surgery was assessed by proteome profiling of blood plasma samples.

Materials and Methods

Plasma samples of healthy living donors (LD) participating in the VAPOR-1 trial were used. Sample points were: before surgery (T0), immediately after surgery (T1), and 24 hours after surgery (T2). LDs were anaesthetised with either propofol (n=19) or sevoflurane (n=17) and matched by age, gender, BMI, comorbidity and medication. Anaesthetic and hemodynamic management was strictly protocolised. Samples were subjected to proteome profiling by mass spectrometry followed by data analysis with MaxQuant software. Student’s T-Test and multiple testing correction were applied to detect significant changes in protein abundance between comparisons.

Results

Quantitative protein identification resulted in detection of 633 plasma proteins. A subset of 28 proteins showed statistically significant (P<0.05) expression level changes between time points. Proteins with over two-fold change comprised a smaller group of nine upregulated targets that are known to be involved in acute phase inflammatory response (CRP, SAA1, SAA2, LBP, SERPINA1, SERPINA3) and tissue regeneration (FGL1, LRG1, MAN1A1). These targets were common in all LDs, except MAN1A1 that was upregulated only in propofol anaesthesia.

Discussion

In this study, we have evaluated the effect of a major surgical intervention in a unique cohort of healthy subjects selected to donate a kidney, using systems biology by analysing individual sequential proteomic profiles. The predominant changes in profiles before and after surgery involved pathways of acute phase response and tissue remodelling. The highest detected changes in protein levels were found to be independent of anaesthesia type, while proteome profiles also displayed a number of moderate level anaesthesia-specific changes. More proteins with statistically significant level changes were detected one day after surgery (T2) when compared to immediately after surgery (T1), in both anaesthesia groups.

Conclusion

This study is a first attempt to gain better insight in molecular effects of surgical intervention in a selected healthy ‘control’ group using systems biology. Quantitative proteome analysis identified upregulated proteins in response to laparoscopic intervention independent of anaesthetic type, which known to be involved in acute phase inflammatory response, immunogenicity and tissue remodelling.

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