Detection of ATP by "in line” 31P magnetic resonance spectroscopy during oxygenated hypothermic pulsatile perfusion of pigs' kidneys

Object: To demonstrate that adenosine triphosphate (ATP), which provides a valuable biomarker for kidney viability in the context of donation after cardiac death (DCD) transplantation, can be detected by means of 31P magnetic resonance spectroscopy (MRS) if kidneys are perfused with oxygenated hypothermic pulsatile perfusion (O2+HPP). Materials and methods: Porcine kidney perfusion was carried out using a home made, MR-compatible HPP-machine. Consequently, kidney perfusion could be performed continuously during magnetic resonance imaging and magnetic resonance spectroscopy recording. 31P MR spectroscopy consisted of 3-dimensional chemical shift imaging (CSI), which allowed for the detection of ATP level in line. 31P CSI was performed at 3tesla in 44min with a nominal voxel size of 6.1cc. Results: 31P CSI enabled the detection of renal ATP when pO2 was equal to 100kPa. With pO2 of 20kPa, only phosphomonoester, inorganic phosphate and nicotinamide adenine dinucleotide could be found. Semi-quantitative analysis showed that ATP level was 1.3mM in normal kidney perfused with pO2 of 100kPa. Conclusions: This combined technology may constitute a new advance in DCD organ diagnostics prior to transplantation, as it allows direct assessment of ATP concentration, which provides a reliable indicator for organ bioenergetics and viability. In this study, kidneys presenting no warm ischemia were tested in order to establish values in normal organs. The test could be easily integrated into the clinical environment and would not generate any additional delay into the transplantation clinical workflo

A new disposable perfusion machine, nuclear magnetic resonance compatible, to test the marginal organs and the kidneys from non-heart-beating donors before transplantation

This article is the first report about our new hypothermic pulsatile perfusion machine (HUG's HPP-machine) for kidney perfusion. This machine will be used for (31)P NMR spectroscopy. The aim is to obtain scores of viability of marginal kidneys and those from non-heart-beating donors (NHBD) before transplantation using HPP as it has been demonstrated necessary in these situations. The most predictable test is the ratio of phosphomonoester on inorganic phosphorus (PME/Pi) that can be obtained from (31)P spectroscopy. The machine has been built to allow perfusion of kidneys in the range of that performed with the traditional Belzer, Mox-Waters machines and others, but compatible with the magnetic fields of the MRI apparatus used for (31)P NMR spectroscopy. In this publication, the technical aspects of this new aerobic HPP-machine compatible with MRI is presented

La viabilité des reins marginaux testée par perfusion de gadolinium sous IRM pendant leur réanimation

INTRODUCTION: Marginal kidneys must be reanimated before their transplantation. Reanimation is conducted with hypothermic pulsatile perfusion. The tests used generally to demonstrate the viability is the vascular resistance which is not convenient for everybody. We have developed a magnetic resonance compatible perfusional technology allowing us to test the organs during the perfusion by Gd-perfusion MRI. METHODS AND RESULTS: We have used pigs' kidneys with no warm ischemic time to establish the basis in a normal kidney. After an eight-hour hypothermic pulsatile perfusion, kidneys are submitted to a Gd perfusion. First, we measure the anatomy of the vessels, then the distribution of Gd in the kidney. We obtain simultaneously a dynamic study of the organs where T0 represents the Gd bolus arrival in the cortex and TP the maximum saturation time of Gd. CONCLUSION: We have observed that a normal T0 is inferior to 30s and TP is inferior to one minute. We have compared these values with ATP resynthesis in these organs and found that they correlate. We hope for the future through that predictive use of Gd-MRI to avoid the clinical use of "too" marginal kidneys or the discard of good kidneys but not corresponding with the vascular resistance theory

Transplantation d'organes avec assistance robotique

Advanced surgical procedures have traditionally been a domain of open surgery. However, minimally invasive approaches are evolving with the development of robotic technology which appears capable to overcome technical limitations of conventional laparoscopy. While traditionally perceived as impossible indications for minimally invasive surgery, reports on robotic organ transplantations have surfaced with promising results

Intra-abdominal cooling system limits ischemia-reperfusion injury during robot-assisted renal transplantation

Robot-assisted kidney transplantation is feasible; however, concerns have been raised about possible increases in warm ischemia times. We describe a novel intra-abdominal cooling system to continuously cool the kidney during the procedure. Porcine kidneys were procured by standard open technique. Groups were as follow: Robotic renal transplantation with (n=11) and without (n=6) continuous intra-abdominal cooling and conventional open technique with intermittent 4°C saline cooling (n=6). Renal cortex temperature, magnetic resonance imaging and histology were analyzed. Robotic renal transplantation required a longer operative time, either with or without the cooling system, compared to the open approach (70.4±17.7 min and 74.0±21.5 min vs. 49.4±12.4 min, p-values<0.05). The temperature was lower in the robotic group with cooling system compared to the open approach group (6.5±3.1°C vs. 22.5±6.5°C; p=0.002) or compared to the robotic group without the cooling system (28.7±3.3°C; p=0.133). MRI parenchymal heterogeneities and histologic ischemia-reperfusion lesions were more severe in the robotic group without cooling than in the cooled (open and robotic) groups. Robot-assisted kidney transplantation prolongs the warm ischemia time of the donor kidney. We developed a novel intra-abdominal cooling system that suppresses the non-controlled rewarming of donor kidneys during the transplant procedure and prevents ischemia-reperfusion injuries. This article is protected by copyright. All rights reserved

Detection of ATP by "in line" 31P magnetic resonance spectroscopy during oxygenated hypothermic pulsatile perfusion of pigs' kidneys

To demonstrate that adenosine triphosphate (ATP), which provides a valuable biomarker for kidney viability in the context of donation after cardiac death (DCD) transplantation, can be detected by means of (31)P magnetic resonance spectroscopy (MRS) if kidneys are perfused with oxygenated hypothermic pulsatile perfusion (O(2)+HPP)

DCD Pigs' Kidneys Analyzed by MRI to Assess Ex Vivo Their Viability

Magnetic resonance imaging (MRI) gadolinium-perfusion was applied in simulated Donation after Cardiac Death (DCD) in porcine kidneys to measure intrarenal perfusion. Adenosine triphosphate (ATP) resynthesis during oxygenated hypothermic perfusion was compared to evaluate the "ex vivo organ viability". Adenine nucleotide (AN) was measured by P nuclear magnetic resonance (NMR) spectroscopy. Whereas this latter technique requires sophisticated hardware, gadolinium-perfusion can be realized using any standard proton-MRI scanner. The aim of this work was to establish a correlation between the two methods

Oxygenated hypothermic pulsatile perfusion versus cold static storage for kidneys from non heart-beating donors tested by in-line ATP resynthesis to establish a strategy of preservation

The scarcity of kidneys for transplantation impels an expansion of the donor source to include the use of organs from Maastricht II and Maastricht I non heart-beating donors. The aim of this study was to establish the best method to preserve kidneys from non heart-beating donors (NHBD): cold static storage (CSS) or perfusion. ATP production during kidney preservation has been retained as a measure of their energetic levels and, consequently, their viability. The presence of warm ischemia with both types of preservation was studied