Study pinpoints reason why transplanted kidneys can be rejected, scientists say

Scientists believe they have found a major reason why transplanted kidneys can be rejected by the body, paving the way for new treatments that may help transplants last longer.

Experts used new imaging techniques to look at the organ’s “plumbing system” to understand what these vessels do during transplantation.

For the study, published in the Journal of Clinical Investigation, scientists at the Wellcome Sanger Institute, University College London (UCL) and the University of Cambridge, studied samples from healthy patients and those whose bodies had rejected a transplant.

The team combined single-cell sequencing – technology that determines the genetic or RNA sequence of individual cells – with powerful 3D imaging to look at the lymphatic vessels in kidney tissue.

These vessels form a network in the kidney that collects and transports fluid, waste and immune cells in the organ.

Researchers discovered that during transplant rejection, the vessels change dramatically.

They spread to deeper parts of the kidney known as the medulla, which does not normally contain lymphatic vessels.

Menna Clatworthy, professor of translational immunology at the University of Cambridge and the Wellcome Sanger Institute, added: “By uncovering how lymphatic vessels change at both the structural and molecular level, we now have a much clearer picture of the immune environment during transplant rejection.

“This could help us identify new therapeutic targets to preserve kidney transplants for longer.”

Meanwhile, the study found that the endothelial junctions, connections between cells that line the blood and lymph vessels that control what passes through the vessel walls, undergo “remodelling” and shift from looking like buttons to tightening up like zippers.

It was also discovered that the balance of T cells, the white blood cells that help fight infection, became disrupted.

Dr Daniyal Jafree, of the Wellcome Sanger Institute and a clinician-scientist at UCL Great Ormond Street Institute of Child Health, said: “You can think of lymphatic vessels as the kidney’s plumbing system, clearing away excess fluid, immune cells and inflammation.

“Until now, we have struggled to really understand what these vessels do in kidney transplantation because they are so difficult to study.

“Using new imaging techniques, we’ve shown that these vessels undergo dramatic changes during rejection and are themselves a target of the immune system.”

David Long, professor of paediatric nephrology at UCL Great Ormond Street Institute of Child Health, and deputy theme lead of the NIHR GOSH Biomedical Research Centre, added: “Our innovative methods have allowed us to clearly demonstrate the important role of lymphatic vessels in transplant rejection.

“By combining single-cell sequencing with advanced 3D imaging, we’ve made a significant step forward in kidney transplant research.”

The kidney is the most commonly transplanted organ in the UK. Figures from NHS Blood and Transplant show more than 8,000 people are on the waiting list.