Harnessing Innovative Transplant Diagnostics to Improve Patient Outcomes

Despite advances in the field of organ transplantation, industry challenges such as a shortage of viable organs for transplantation remain. It’s an unfortunate truth: the number of patients who need transplants far exceeds the number of donor organs currently available. According to data from the United Network for Organ Sharing (UNOS), the need for organ transplants is steadily rising, with over 100,000 people currently on the waitlist in the U.S. alone. The list continues to grow, with a new person added every 10 minutes. While the number of organ transplants performed has also been increasing, reaching a record high of over 46,000 in the U.S. in 2023, there’s a still a significant ongoing gap between supply and demand for organs. 

Even for those who successfully receive a compatible donor organ, it’s only one part of a laborious transplant journey that often presents additional struggles, such as balancing the risk of organ rejection with the side effects of the drugs that are prescribed to prevent rejection. Fortunately, innovative transplant diagnostics and novel paradigms that give a clearer picture of a recipient’s immune system at various phases of the transplant journey can enable transplant teams to mitigate some of these challenges and make more accurate and faster donor assessments, as well as more informed and patient-centric decisions post-transplant.

Pre-transplant challenges

The first step in the transplant process is placing the patient on the transplant waiting list. Data shows that finding a potential kidney donor could take up to three years on average and 17 people die each day waiting for an organ transplant. While supply and demand plays a role in the wait time, so does the immunologic assessment between patient and donor to ensure that the organ transplant is successful. On average, between 10% to 15% of kidney transplant recipients experience a rejection episode in the first year  – rising to up to 40% in heart transplant recipients.  Fortunately, innovative pre-transplant diagnostics can increase the chances of a successful transplant. 

The pre-transplant screening process involves three main types of clinical diagnostics as part of determining transplant eligibility and needs, including blood-group testing, human leukocyte antigen (HLA) typing and HLA antibody testing. HLA proteins are responsible for the regulation of the immune system and help the body determine self from non-self. Different people have different types of HLA, and when the body sees an HLA protein it doesn’t recognize, it can produce an immune response against the foreign cells or tissues containing those proteins. 

Prior to transplantation, clinicians use HLA typing tests to determine the HLA type of each recipient and donor. To help lower the risk of organ rejection, it is crucial to find as close an HLA match between the donor and recipient as possible. While HLA typing has been around for decades, more recent innovations in next-generation sequencing (NGS) have provided more accurate, high-resolution data. This can enable clinicians to make more precise assessments of donor and recipient compatibility.

HLA antibody testing is used pre-transplant to determine whether the recipient’s body already has antibodies formed against a potential donor’s HLA proteins. Patients may develop antibodies from previous transplants, blood transfusions or pregnancy, for example. Similar to HLA typing, innovation in HLA antibody testing has provided clinicians with more precise data to enable better decision-making.

There is no single definitive test that can provide all the answers, but these diagnostic tests offer more data to help clinicians increase the probability for a successful transplant and reduce the risk of organ transplant rejection, particularly as the number of people waiting for a transplant continues to increase.

Assessing transplant risk with virtual crossmatching 

Traditionally, a physical crossmatch test is performed prior to the transplant surgery to verify that the donor organ is compatible, and the recipient’s body will not immediately reject it. Typically this involved mixing donor cells and recipient serum (the component of blood where antibodies are detected) and looking to see if the patient is reactive against the donor. Some newer protocols allow for “virtual” crossmatching, which is an alternative approach to assessing compatibility prior to transplantation. 

Unlike a physical crossmatch, a virtual crossmatch does not require viable donor cells, but instead relies on complete HLA typing of the donor and highly accurate antibody assessment of the recipient. Removing the safety net of the physical crossmatch means that we are more reliant than ever before on the accuracy, reliability and reproducibility of the diagnostics testing upon which virtual crossmatching so heavily relies. 

Virtual crossmatching can help streamline the assessment process as it can be performed in just minutes, enabling swifter transplant decision making. Donor organs need to be transplanted within hours to ensure viability, so time is precious. Every minute saved helps to increase the likelihood of a successful transplant. That makes virtual crossmatching particularly helpful in determining whether a donor organ located in a different geographical area than a potential recipient would be a suitable match in a timely manner.

Post-transplant monitoring

The journey is not over once the transplant surgery is complete. The post-transplant phase can present another set of challenges and potential complications for organ transplant recipients, who require lifelong immunosuppressive drugs to reduce the risk of rejection and often invasive monitoring to assess the health of their transplanted organ. An organ transplant is not a cure; it is a lifelong treatment that requires ongoing surveillance. Invasive biopsies and aggressive immunosuppression to prevent rejection can have a tremendous impact on both the physical and mental health of a patient due to uncertainty and heightened anxiety surrounding the results.

Fortunately, novel transplant diagnostics can help make monitoring more convenient and less invasive. For example, urine-based biomarker tests can provide valuable data about the risk of organ rejection in as little as 24 hours. Blood tests such as donor derived cell-free DNA also provide useful information, and offer a less invasive option, and better patient experience in contrast with invasive biopsies. 

These innovative, lower-cost and non-invasive testing options can also help address health disparities by expanding access to care since samples can be collected at a doctor’s office or local clinic. This can also help reduce the financial burden for patients, who might otherwise have to travel long distances to a transplant center.  In the future, these non-invasive samples may also be collected at home or elsewhere remotely, offering further convenience for patients who may not have the means to travel long distances to healthcare facilities. 

Informing personalized approaches to improve patient outcomes 

The need for innovative tests that inform more personalized approaches to post-transplant management is greater than ever. Significantly reducing the risk of side effects or rejection can be transformative, both in terms of improving patient health and health economics, as treatment of rejection or dealing with unwanted side effects of medication can be financially burdensome. 

With this in mind, the newest wave of transplant diagnostic solutions aim to enable clinicians to tailor immunosuppression regimes based on a patient’s individual risk of rejection, allowing for more targeted and optimized patient care versus relying solely on standard protocols which are broadly applied to all patients. 

That said, widespread adoption of these predictive tests hinges on a variety of factors, including more research, clinical use cases and reimbursement through both private and public payors. Collaboration among clinicians, lawmakers, diagnostic solution providers and patients is required to harness their full potential. The first step is raising awareness and promoting adoption of innovative solutions within the transplant community, emphasizing the crucial role novel diagnostics play in alleviating challenges along the transplant journey.

Photo: Murat Göçmen, Getty Images

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