Biotechnology to reduce the risk of kidney transplant failure and adverse events related to immunosuppression

According to data collected by World Kidney Day, 10% of the global population suffers from chronic kidney disease. An increasingly pressing public health problem that already affected more than 850 million people worldwide in 2019 and resulted in over 3.1 million deaths.

Chronic kidney disease can be fatal if not given proper attention and management, as evidenced by it already being the eighth leading cause of death worldwide. The non-profit organization reports that high blood pressure (hypertension) and diabetes (the second most common cause of end-stage renal disease in most developed countries) are the most frequent causes of kidney disease.

The current picture reveals an alarming horizon: projections indicate that chronic kidney disease will be the fifth leading cause of death globally by the year 2040. Kidney transplantation emerges as the chosen treatment in cases of chronic kidney disease or end-stage renal disease. Current figures indicate that around 1.5 million people worldwide live with a kidney transplant, but 50% of transplants are lost within 10 years.

This is a problem to which biotechnology is offering a response, as evidenced by the work carried out by Biohope, a biotechnology company focused on precision medicine in the areas of immunosuppression and autoimmune diseases.

Biohope is developing Immunobiogram® (IMBG), a kit to determine a patient's sensitivity to a panel of the most commonly used immunosuppressive drugs in blood, in order to personalize each patient's immunosuppressive therapy throughout their life. And today, on World Kidney Day, we interview its founder and CEO, Isabel Portero.

AseBio: Around 1.5 million people worldwide live with a kidney transplant. What are the main risks they face?

Isabel Portero: End-stage renal failure is the final stage of chronic kidney disease, and if left untreated, it leads to premature death. Although it can be managed with dialysis, kidney transplantation is currently the preferred therapeutic option because it provides higher survival rates, significant improvement in patients' quality of life, and greater cost-effectiveness.

Each year, 150,000 solid organs are transplanted worldwide, of which 100,000 are kidney transplants. In Spain, in 2023, 3688 kidney transplants were performed.

Transplanted patients have a persistent risk of organ rejection due to immune-mediated kidney injury. The recipient's immune system may recognize the donor's specific antigens expressed by the organ as foreign and develop an immune response against them, causing tissue damage to the organ and potentially leading to transplant failure. Additionally, immunosuppressive drugs, used to prevent rejection as much as possible, increase the risk of infections and cancer, two major issues also faced by these patients.

AseBio: What is the current situation in terms of immunosuppression in the field of kidney transplantation?

Isabel Portero: Transplant recipients are treated with a combination of immunosuppressive drugs to avoid the risk of graft rejection and achieve greater long-term survival of the transplanted organ.

It is estimated that around 30-50% of patients will lose the kidney allograft in the following 10 years after transplantation, often due to organ rejection or complications associated with chronic use of immunosuppressive drugs. The loss of the organ would necessitate the patient's return to dialysis or the need for a new transplant.

The physician decides on a therapeutic regimen that includes one or more immunosuppressants, with the main clinical goal being graft viability, i.e., preventing rejection. At the same time, they attempt, as much as possible, to use the least amount of immunosuppression (in terms of drugs and doses) to prevent rejection while avoiding the risks of over-immunosuppression.

Side effects related to immunosuppression also have a significant impact on patients' health; the leading causes of death among patients are cancer (29%), cardiovascular disease (23%), and infection (12%), mostly related to immunosuppression and chronic inflammation.

Despite the high demographic and clinical heterogeneity of kidney transplant donors and recipients, the selection and dosing adjustment of immunosuppressive drugs are essentially empirical. Treatment is adjusted throughout follow-up considering target drug concentrations in peripheral blood (plasma levels) and the occurrence of medication-related side effects. However, toxicity related to immunosuppressive treatment and organ rejection still occur within acceptable concentration ranges.

Adjusting immunosuppressive therapy is considered by clinicians following transplanted patients as one of the most complex aspects of treatment. Although combination immunosuppressive therapy is commonly used in clinical practice, clinicians typically modify treatment on individual drugs, with few objective clues or biomarkers to help the physician choose which drugs to act on.

For these reasons, the current strategy may lead in a considerable number of cases to insufficient immunosuppression or excessive immunosuppression.

Until now, there hasn't been a test available in clinical practice that could predict the patient's response to each immunosuppressive drug, so this information can complement the information available to physicians, aiding them in decision-making regarding the adaptation of immunosuppressive therapy for each patient.

There is, therefore, an unmet clinical need for tools that allow more individualized decision-making, based on the patient's immunological risk profile and response to immunosuppressive treatment.

AseBio: You have developed and validated Immunobiogram®, a clinical test that only requires a blood sample to analyze the response of individual immune cells from the patient to different kidney transplant treatments. What does this test entail?

Isabel Portero: The Immunobiogram® is a novel tool developed by the company Biohope Scientific Solutions for Human Health SL to enable the in vitro measurement of the response to individual immunosuppressants commonly used in the treatment of patients with a kidney transplant.

It is a functional test that predicts the response to immunosuppressive treatment by measuring in vitro the metabolic activity of PBMCs (peripheral blood mononuclear cells) from patients, immunologically activated, in response to immunosuppressive drugs.

The Immunobiogram is designed for use in patients treated or who may receive treatment with the immunosuppressive drugs tested in the Immunobiogram.

AseBio: What benefits does the information obtained through Immunobiogram offer from the perspective of the medical professional?

Isabel Portero: The potential benefits of Immunobiogram are based on the possible reduction of transplant failures due to rejection or adverse events related to immunosuppression, thanks to a more individualized adjustment of immunosuppressive medication.

AseBio: From the perspective of healthcare systems, what benefits can this test provide?

Isabel Portero: The use of Immunobiogram could generate savings for the healthcare system over a five-year period linked to the reduction of transplant complications. From a social perspective, gains could be made in terms of years of life gained and quality of life for patients.

Therefore, the use of Immunobiogram could contribute to a reduction in the risk of transplant failure and adverse events related to immunosuppression, with a gain in quality of life, as well as savings for the healthcare system.

Currently, the technique is already starting to be used in the main hospitals performing kidney transplants in Spain.