The search for predictive markers associated with allograft rejection is a key focus in transplant research. Post-transplant monitoring relies mainly on serial serum creatinine (Cr) measurements and in biopsies.
- Serum Cr level is a highly insensitive indicator of the degree of damage in the kidney. It has a lag time of weeks to months while on-going damage is occurring, and changes are non-specific with regards to the cause of the injury.
- Surveillance biopsies are the gold standard to detect graft rejection, but they are performed infrequently after kidney transplantation. Biopsies are invasive, expensive, and subject to inter-grader variability of approximately 30%; therefore, performing invasive biopsies is not suitable for frequent monitoring.
- To date, the only validated and accepted marker by the clinical community is the -de novo – appearance of DSA (Donor Specific Antigens), which advise about the risk of graft rejection.
- Currently, there is no validated test to measure or monitor the adequacy of the immunosuppression regimen. The lack of this test may result in under-immunosuppression and cause graft rejection, or in over-immunosuppression causing a higher risk of opportunistic infections and malignancies.
- Immuknow® is an IVD approved by the US Food and Drug Administration (FDA) (not in the EU) under the 510K pathway in 2002. This bioassay quantifies the amount of intracellular ATP that is released from CD4+ T cells in response to a non-specific mitogenic stimulus. It only identifies if there is a certain risk of rejection (due to underimmunosuppression), but it doesn´t provide a specific result regarding the sensitivity/resistance profile of each patient to the IMSs they are taking.
- Other tools (like Trugraf) have been developed to tests on gene-expression “signatures”, but again they only identify if there is a certain risk of rejection and only differenciate between a state of trasplant eXcellence (TX= adequately immunosuppressed) from a not-TX situation.
- Molecular biomarkers have been studied in the graft, urine and blood of kidney transplant recipients, but recent reviews have highlighted the need for robust multicenter validation studies, and underscored the potential role for biomarker monitoring of immunosuppressive therapy and transplant outcomes. They are not used in daily clinical practice (Menon 2017).