New treatment improves viability of donor kidneys affected by ischaemia

Matilda Olsson, research nurse, Clara Paul, transplant surgeon, and Carl Raihle, consultant physician specialising in kidney transplantation.

Researchers at Skåne University Hospital have successfully treated and transplanted donated kidneys with ischaemic injury. In the longer term, the findings may lead to a higher number of successful kidney transplantations and a reduced need for dialysis.

The treatment, which was evaluated within a clinical study, protects renal cells during periods of oxygen deprivation and reduces the risk of rejection of the transplanted organ.

“This is, to our knowledge, the first-in-human study evaluating this treatment in 18 patients undergoing kidney transplantation. The results are encouraging and indicate that the treatment is safe and shows promise,” says Clara Paul, transplant surgeon, Section Head at Skåne University Hospital and principal investigator of the study.

The study has now been completed, and the initial results were presented at the international conference ASN Kidney Week, organised by the American Society of Nephrology (ASN), in the United States.

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The results from the preclinical development phase have also recently been published in the scientific journal American Journal of Transplantation (AJT).

Ischaemia causes complications

“The method is innovative because we treat the organ itself rather than the patient. By attenuating the immune response during the first critical minutes after blood flow is restored, the kidney is given time to recover and preserve its function,” says Clara Paul.

A common challenge in organ transplantation is cellular damage caused by oxygen deprivation, known as ischaemic injury. This occurs because there is often a prolonged interval between retrieval of the kidney from the donor and transplantation. The problem is particularly pronounced in kidneys donated after the donor has died, but even organs from living donors are exposed to several hours without oxygen.

Protection of renal cells

“The injury that occurs when blood flow is re-established is related to the fact that, during ischaemia, renal cells undergo changes in both morphology and surface structure. When circulation is restored, the recipient’s immune system may perceive these altered cells as abnormal and elicits a rapid immune response. This rapid reaction can impair graft function in both the short and long term,” explains Clara Paul.

The treatment involves a single-dose intervention administered directly to the kidney immediately prior to transplantation and before reperfusion. The investigational drug creates a transient protective barrier on the surface of renal cells and blocks the initial, intense interaction with the recipient’s immune system—an interaction that would otherwise often trigger inflammation and tissue injury.

Increasing the number of transplantable kidneys

In the longer term, the method may increase access to donor kidneys, as organs that were previously considered unsuitable for transplantation due to ischaemic injury may prove to be of sufficient quality for clinical use.

All patients included in the study have also been followed up for one year.

“The treatment appears to provide a better initial outcome and has demonstrated an acceptable safety profile over one year of follow-up. One year after transplantation, the patients show preserved renal function and no unexpected complications,” says Clara Paul.

Facts

The treatment has been developed in Sweden through a collaboration between five researchers at Lund University and Uppsala University.
The researchers are also co-founders of the company that is continuing the development of the technology.