Transbiohope | Transbiohope
Transbio project, oriented to the development of an in vitro diagnostic kit for the treatment of chronic rejection with immunosuppressants. H2020 program of the European Union
"trasplante riñón” “diagnóstico in vitro” “in vitro diagnosis” “trasplante renal” “H2020” “European Commission project” “renal transplant” “kidney transplant” “start-up” “Tres Cantos” “biomedicina” “biomedicine” “biotechnology” “immunobiogram” “inmunobiograma” “tratamiento inmunosupresores” “Treatment with immunosuppressants”
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End-stage kidney disease (ESKD) is the last stage of a chronic kidney disease, which if not addressed leads to premature death and, although it can be addressed by dialysis, kidney transplantation is the preferred treatment due to better survival rates, improved quality of life and cost efficiency.

 

However, although surgical techniques and postoperative care have greatly advanced, renal transplantation is not empty of challenges. The most important challenge is to achieve the long-term survival of the transplanted organ (also known as graft or allograft).

Graft survival depends on the ability of the recipient of not rejecting the donor organ. Rejection is a naturally occurring process triggered by a biological response of the immune system, which main function in the body is to defend it against infectious organisms and other invaders.

The most important challenge in renal transplantion is to achieve the long-term survival of the transplanted organ
About 50% of transplanted kidneys are lost during the first 10 years and this is because of an immune response usually described as chronic rejection

As such, the immune system is prepared to reject a donor organ, something that is nowadays prevented by prescribing immunosuppressive therapies (drugs that suppress/reduce the effectiveness of the immune system) to the patients for their whole life. However, although immunosuppressive therapies have represented a huge step forward in organ transplantation, their use still entails important problems. On one side, suppressing the immune system implies severe side effects like opportunistic infections, cancer and other severe pathologies. On the other side, even under immunosuppressive therapies, about 50% of transplanted kidneys are lost during the first 10 years and this is because of an immune response usually described as chronic rejection. Therefore, the major challenges in kidney transplantation deal with avoiding the side effects associated with immunosuppressant drugs and avoiding chronic rejection. The key question is… how this can be made possible?

To answer this question, we should first explain that patients undergoing a kidney transplant can show 3 different main
immune response profiles in the long term (~10 years after transplantation), as graphically shown below:

Every patient requires different immunosuppression type and load,
according to their immune response profile

50%

CLASSICAL RESPONSE

Graft in not rejected but requiring immunosuppressive therapy for the whole patient´s life

40%

CHRONIC REJECTION

Long-term loss of function in transplanted organs, even under immunopressive therapy

10%

OPERATIONAL TOLERANCE

Patient who develop immunological unresponsiveness (tolerance) towards graft, so for whom the immunosuppressive therapy can be withdrawn.

The main goal in organ transplantation is to identify the optimal immunosuppressant therapy to assure the effective prevention of rejection, while side effects are minimized

In accordance with these three immune response profiles, the immunosuppressive therapy should be adapted to avoid organ rejection and reduce treatment side effects:

  • Patients with a classical response (50%) should reduce their immunosuppressant treatment to the actual patient needs.
  • Patients whose outcome is chronic rejection (40%) could be prevented by the early identification of this phenomenon and adjustment (increase/change) of immunosuppressive therapy.
  • Patients showing an operational tolerance (10%) could be considered to gradually reduce or withdrawn immunosuppressive drugs, without compromising graft survival.

 

Accordingly, the main goal in organ transplantation is to identify the optimal immunosuppressant therapy to assure the effective prevention of rejection, while side effects are minimized.

However, currently there is no way to determine in an objective way the immune profile of patients that undergone a transplant, and the gradual reduction of mediations and evaluation of graft function along time is performed only based on empirical observations.

In one hand, patients at risk of chronic rejection or those developing any kind of operational tolerance could be at huge risk under this try and error approach, as it can lead to the irreversible organ rejection. So, majority of doctors do not recommend to withdrawn the medication even for patients suspicious of having developed operational tolerance and need objective tools to choose the best medication combo possible to treat an evolving rejection process.

On the other hand, for those patients with a classic immune response profile, side effects could be reduced significantly if a rational approach is used in the selection of the optimal treatment for the specific patient needs (personalized treatment).

For all of them, the previous determination of the effects of different drug combinations in the “immune response profile” of the patient and monitorization of the evolution along time, would led to rational and specific medication adjustments.