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Faculty of Medical Sciences

Impact of Hydrogen Sulphide on Warm Ischemic Kidneys

Tourdanov, I. (Ingrid) (2019) Impact of Hydrogen Sulphide on Warm Ischemic Kidneys. thesis, Medicine.

Full text available on request.

Abstract

Introduction Due to an organ shortage problem in renal transplantology, donation after cardiac death (DCD) kidneys are used to fill the demand gap. They however need to be subjected to long warm ischemic times, which causes ischemia induced injury. In order to tackle this problem, this study investigated whether administering hydrogen sulphide (H2S) to porcine kidneys will protect the organ during ischemic time and lead to a better kidney function and diminished damage, compared to controls. Methods In total 6 porcine kidneys were used for this project. The experimental group (n=2) consisted of kidneys treated with a bolus of H2S of 100 ppm prior to undergoing room temperature ischemia of 3 hours. The control group (n=2) was also left at room temperature ischemic conditions for 3 hours, however didn’t receive a prior bolus of H2S. The reference group (n=2) was represented by kidneys treated with 3 hours of hypothermic machine perfusion (HMP). All groups subsequently underwent 4 hours of normothermic machine perfusion (NMP), during which amongst others kidney function, damage markers aspartate aminotransferase and lactate dehydrogenase (AST, LDH), perfusion parameters and oxygen consumption were measured to assess the level of preservation of the kidney and its functionality. Moreover, biopsies were taken at different time points for histological images and ATP determination. Results were statistically analysed using a linear mixed model. Results Kidney function, as measured by creatinine clearance was the primary outcome in this project. Creatinine clearance was on average highest in the control group (85% higher than the experimental group and 90% lower than the reference group), however this difference was not statistically significant (P= 0.132). AST levels were on average lowest in the experimental group (57.92 mmol/L) and LDH levels lowest in the reference group (198.42 mmol/L), while both damage markers were highest in the control group (average of 149 mmol/L for LDH and 282 mmol/L for AST). This difference was also not statistically significant (P=0.743 for AST and P=0.862 for LDH). Oxygen consumption was on average highest in the experimental group (10% higher than the reference group and 5% higher than the control group). This difference is statistically significant (P=0.000). Conclusion The results obtained from this series of experiments are as of yet inconclusive as they come from a sample of only two subjects per group. Some results could suggest that particular protective mechanisms of H2S took place, most other findings however, were inconsistent with the hypothesis that H2S perfusion protects kidneys from ischemic damage. Further research involving larger subject groups and shorter warm ischemic times is required to make a definite statement about the extent of organ protection that can be achieved in these specific conditions by administering H2S.

Item Type: Thesis (Thesis)
Supervisor name: Leuvenink, Prof. dr. H. and Goor, Prof. dr. H. van and Department of Surgery and University Medicical Center Groningen
Faculty: Medical Sciences
Date Deposited: 25 Jun 2020 10:57
Last Modified: 25 Jun 2020 10:57
URI: https://umcg.studenttheses.ub.rug.nl/id/eprint/1756

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