More donor kidneys and livers through improved selection

Donor blood plays a vital role not only in critical care but also in supporting diverse research initiatives such as organ transplantation procedures.

The demand for donor organs significantly outstrips the supply, leading to lengthy waiting lists. Consequently, scientists are actively investigating the criteria that determine the suitability of a donor organ for transplantation. Among them is Jason Doppenberg, a technical physician at the Leiden University Medical Center (LUMC), who utilizes donor blood from Sanquin in his research.

Dr. Doppenberg, a postdoctoral researcher and coordinator of the Organ Preservation and Regeneration Unit at the LUMC, currently focuses primarily on donor livers and kidneys, both of which face substantial waiting lists. At the end of last year, 77 patients in the Netherlands were awaiting a liver transplant, and a staggering 1,074 were on the kidney transplant list. Imagine the impact if donor organs currently deemed unsuitable could still be safely used. This is the very possibility Dr. Doppenberg has been exploring for years. "Consider organs from donors with conditions like diabetes, advanced age, obesity, and/or a history of smoking. We typically wouldn't use these, even though their quality might still be acceptable. That's why we're identifying parameters to accurately assess their quality."

Warm perfusion technique

Historically, only organs from brain-dead donors were considered viable for transplantation. However, it is now also possible to transplant organs from donors who have died following cardiac arrest, a process known as donation after circulatory death (DCD), as Dr. Doppenberg explains. "This advancement is partly due to the development of warm perfusion. This technique involves a perfusion machine that pumps a warm fluid through the donor organ, maintaining its activity and good condition. This warm fluid, or perfusate, contains red blood cells obtained from Sanquin blood donors." The advent of warm perfusion allows Dr. Doppenberg and his colleagues to conduct tests to ascertain the functionality of seemingly less optimal donor organs. For this scientific research, they rely on red blood cells donated through Sanquin. Prior to donation, individuals are specifically asked for their consent to use their red blood cells for this purpose.

Identifying key parameters

The researchers in Leiden are working to pinpoint parameters that can reliably indicate the quality of a donor organ. According to Dr. Doppenberg, they have made significant progress in this area for donor livers. "A healthy liver produces bile. We collect this fluid, and its composition can predict the success of a liver transplant. For instance, a higher pH, lower glucose levels, and a greater bicarbonate concentration are favorable indicators. We have been applying this knowledge in clinical practice for several years." However, the situation is different for kidneys, which produce urine. "The composition of urine provides limited information about the outcomes of a kidney transplant," the technical physician clarifies. This is why he is seeking alternative parameters that can accurately reflect the quality of a donor kidney. This investigation has yielded some promising results. It involves blood gas parameters and metabolism within the kidney."

Optimizing resource use and rejuvenation strategies

Dr. Doppenberg emphasizes that this research is made possible in part by the donor blood provided by Sanquin. To minimize the waste of this valuable resource, the scientists handle it with utmost care. For example, they have refined the blood storage protocols. Given the limited shelf life of blood, the same blood is now used for testing both donor livers and kidneys. Previously, separate storage led to greater blood wastage. Dr. Doppenberg explains, "Furthermore, we wash out the perfusate after use, retaining only the red blood cells. We can then reuse these for another organ. We are also exploring methods to extend the storage life of older red blood cells by 'revitalizing' them. One possibility we are considering is rejuvesol, a substance that boosts the energy supply of red blood cells."

Medicines and stem cells: future regeneration strategies

The research undertaken by Dr. Doppenberg and his colleagues aims to refine the selection process for donor organs, ultimately increasing their availability. Looking ahead, he envisions further advancements: "We are exploring whether organs that don't meet the enhanced selection criteria can be made suitable for transplantation through regenerative medicine. For instance, fatty livers – a condition affecting approximately 20 percent of the population – are currently unusable. However, if the fat can be removed, these organs could become viable for transplant. Similarly, if a donor kidney exhibits insufficient clearance, treatment with medication or stem cells prior to transplantation might restore its function. While these approaches are still in the planning stages, they represent exciting future possibilities."

Not-for-transfusion blood products

Sanquin prioritizes the use of residual blood products, deemed unsuitable for transfusion, for the provision of not-for-transfusion (NFT) blood products. This includes blood remnants in test tubes after donor infectious disease screening and buffy coats. However, some research necessitates the use of a portion or even a full blood donation when residual products are insufficient. In such exceptional cases, ethical approval from a medical ethics committee of an academic center is required. The NFT physician, in collaboration with the medical director, assesses whether Sanquin can approach donors for research-specific donations, ensuring that the blood supply is not compromised. Dr. Doppenberg's research exemplifies this process, allowing Sanquin donors to contribute to addressing the critical shortage of transplantable organs. All participating donors provide separate informed consent for this specific use of their donation.