Hydrogen Gas Does Not Ameliorate Renal Ischemia Reperfusion Injury in a Preclinical Model

Abstract

In renal transplantation, ischemia reperfusion injury impairs early graft function and can reduce long term graft survival. Hydrogen has antioxidant and anti-inflammatory properties that can reduce the effects of ischemic injury. The aim of this study was to examine the effects of hydrogen gas administered during reperfusion in a preclinical model of kidney ischemia reperfusion injury. Porcine kidneys underwent 15 min of warm ischemia followed by 22 h of cold ischemia. They were then reperfused for 6 h with whole autologous blood on an ex vivo reperfusion circuit. Paired kidneys were randomized to control (n = 6) (25% oxygen, 5% carbon dioxide, 70% nitrogen) or hydrogen (n = 6) (2% hydrogen, 25% oxygen, 5% carbon dioxide, 68% nitrogen) groups. Tissue, urine, and blood samples were collected at baseline and hourly throughout the reperfusion period. Baseline measurements were similar across groups. Following perfusion, there was no significant difference between control and hydrogen groups in urine output (693 mL vs. 608 mL, P = 0.86), renal blood flow (105.9 vs. 108 mL/min/100g, P = 0.89), acid-base homeostasis, or creatinine clearance. There was a significant increase in cytokine levels from baseline to 6 h in both groups (IL-1β P = 0.002; IL-6 P = 0.004; IL-8 P = 0.002). However, there were no significant differences in levels of inflammatory cytokines (IL1β, IL-6, and IL-8) between the groups. The administration of hydrogen gas did not improve renal function, reduce oxidative damage, or inflammation during the reperfusion of ischemically damaged kidneys.

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“…The determination of has been performed in numerous preclinical and clinical NMP studies, which have focused on therapeutic strategies [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ], the ideal NMP experimental setup [ 42 , 43 , 44 , 45 , 46 , 47 ], or the performance of NMP compared to other preservation methods [ 48 , 49 , 50 ], among others. In these studies, either Fick’s principle (e.g., [ 35 , 42 ]) or the simplified form, the arteriovenous pO 2 difference without consideration of hemoglobin concentration (e.g., [ 37 , 39 ]), served as the basis for calculation.…”

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“…This suggested that both inhalation of hydrogen gas and administration of hydrogen-containing solution contribute equally to eliminate excessive ROS and preserve IR-injured organs . However, hydrogen gas administration showed no significant improvements in renal function and inhibitory effects in inflammation and oxidative damage during reperfusion period, and this potential mechanism remains to be elucidated . Unlike hydrogen, nitric oxide, hydrogen sulfide, and carbon monoxide are endogenous substances and play important roles in cellular signaling transduction and regulation of cell cycle, apoptosis, and oxidative stress .…”

“…25 However, hydrogen gas administration showed no significant improvements in renal function and inhibitory effects in inflammation and oxidative damage during reperfusion period, and this potential mechanism remains to be elucidated. 26 Unlike hydrogen, nitric oxide, hydrogen sulfide, and carbon monoxide are endogenous substances and play important roles in cellular signaling transduction and regulation of cell cycle, apoptosis, and oxidative stress. 27 Multiple studies demonstrated that restraining endogenous nitric oxide synthase could exacerbate IR injury, indicating that NO has potential in treating IR injury.…”

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“…Sarah A. Hosgood et al of the University of Cambridge, Addenbrookes's Hospital, Cambridge, UK, investigated if hydrogen gas can ameliorate renal ischemia reperfusion injury in a porcine model. Porcine kidneys underwent 15 minutes of warm ischemia followed by 22 hours of cold ischemia.…”