Tissue pH in human kidney transplants during hypothermic ischemia

Area of Science:

• Biomedical Engineering
• NMR Spectroscopy
• Transplant Medicine

Background:

• Hypothermic storage is crucial for kidney transplant viability.
• Assessing transplant health non-invasively remains a challenge.
• Preservation solutions like HTK aim to minimize ischemic injury.

Purpose of the Study:

• To investigate the utility of ex vivo NMR spectroscopy for monitoring pH in human kidney transplants.
• To correlate pH measurements with transplant function and predict acute tubular necrosis (ATN).
• To evaluate the role of pH and the nucleotide pool in ischemic injury during hypothermic storage.

Main Methods:

• Ex vivo 1.5 T 1H and 31P NMR spectroscopy on 67 human kidney transplants.
• Storage in histidine-tryptophane-alpha-ketoglutarate (HTK) solution.
• pH estimation using chemical shifts and titration studies; prediction of ATN via metabolite ratios (PME/Pi, gamma-NTP/Pi).

Main Results:

• Cytosolic pH was similar in kidneys with immediate function (6.86±0.10) and ATN (6.84±0.10).
• A consistent monoexponential pH decay was observed (0.14±0.07 h(-1)).
• Grafts with immediate function showed higher PME/Pi and gamma-NTP/Pi ratios, indicating a larger nucleotide pool.

Conclusions:

• Non-invasive intra- and extracellular pH monitoring is feasible during hypothermic storage.
• The pH gradient reflects the preservation medium's buffer capacity.
• Acidification is not the primary cause of ATN in HTK storage; the nucleotide pool is key to reversible ischemic injury.