Preprint: protein profiles in pig kidneys moved closer to controls three months after perfusion with clot-dissolving drugs

Preprint: protein profiles in pig kidneys moved closer to controls three months after perfusion with clot-dissolving drugs

A preprint published on Research Square on September 11 examined pig kidneys after uncontrolled circulatory arrest. The authors followed four treated kidneys, collecting tissue samples at retrieval, after each perfusion phase, and three months after transplantation back into the same animal. For comparison, four kidneys from living donors were transplanted using the same surgical protocol. In total, 8 011 protein groups were measured.

When circulation stops, the kidney is left without oxygen for several hours. Fibrin and red blood cells can become trapped in small vessels. Fibrin forms a mesh that retains blood cells, reducing blood flow through some capillaries, the smallest blood vessels. This can allow injury to persist after blood flow through the larger vessels has been restored.

The researchers injected lys-plasminogen, the precursor of the fibrin-cleaving enzyme plasmin, tissue plasminogen activator tPA, and antithrombin into the renal artery. They then placed the organ on machine perfusion, pumping solutions through it outside the body during cold and warm phases before transplanting it back into the pig.

Within a preselected panel of 93 proteins, 39 changed during perfusion after adjustment to reduce the risk of chance findings from multiple tests. For five common plasma proteins, 91% of the total decrease occurred during the initial flush. Fibrinogen chains and plasminogen continued to decrease during the cold phase in all four kidneys. The authors attribute this difference to the cleavage and removal of fibrin fragments during perfusion.

At three months, the overall protein profiles of the treated kidneys had moved closer to those of kidneys from living donors, although differences remained. Levels of proteins in the extracellular matrix, the tissue’s supporting network, also increased; the authors interpret this as remodeling after injury. An earlier study by the same group had already described the function of kidneys transplanted this way over three months. The current preprint adds a timeline of tissue changes from retrieval to the three-month timepoint.