Evaluation of Immunobiogram® as a Tool in Adjustment of Immunosuppressant Therapy for Renal Transplant

Rejection in renal transplants is a major problem unsolved in the long term, as 30-50% of
patients lose their kidney due to rejection, or rejection mechanisms are involved elsewhere.
One of the presumed key factors that may deliver such bad outcomes is the difficulties to
personalise immunosuppressive treatment; a medical need that currently relies on
immunosuppressive levels for some medications (pharmacokinetics), clinical guideline
recommendations, adverse events profiles and some expensive biomarkers which are not widely
used. Immunobiogram® (IMBG) is a tool that evaluates the sensitivity/resistance profile of
patients to each of the most widely used and representative immunosuppressant drugs (IM).
Thus, IMBG offers information that could become pivotal in clinical management of renal
transplanted patients, if its potential benefits are proven. In this clinical study, a
technology validation will be performed in which the robustness of the bioassay will be
evaluated; and a correlation between the current clinical prognoses of each patient and
resistance patterns will be explored.

Inclusion Criteria:

- Age > 25 years and < 70 years.

- Male and Female.

- Renal transplant performed at least 1 year before inclusion.

ARM 1:

- Bad clinical evolution: patients with renal dysfunction and positive biopsy to
rejection OR significant increase in strength of DSA expressed as Luminex MFI.
Specifically, the following two criteria must comply:

- Renal function progressive deterioration, with significant creatinine increase of
at least 15% for 18 months and/or proteinuria over > 500 mg/day or ratio
protein/creatinine> 500 mg/g DE NOVO or increase in 50%.

- Biopsy in the last 12 months that shows positive signs attributable to any kind
of immunological response compatible with any type of rejection AND/OR at least
50% increase in strength of DSA expressed as Luminex MFI in comparison with
previous determination and always at titers more than 3000UI.

- Good clinical evolution: patients without rejection episodes, negative DSA, stable
renal function and no changes in treatment in the past 12 months. ALL the following
criteria must apply

- Stable renal function in the past 12 months

- NO DSA titers

- No history of previous rejection episodes

- Stable immunosuppressive medication (No change in prednisone or MPA dose and
tacrolimus dose with changes <20% of the dose) in the past 12 months

ARM 2:

- Stable renal function

- No DSA titers

- No history of previous rejection episodes

- Stable immunosuppressive medication (No change in prednisone or MPA dose and
tacrolimus dose with changes <20% of the dose) at least in the past 18 months

Exclusion Criteria:

- Rejection of informed consent

- Active systemic infections that needed antimicrobial treatment in the past two months

- Active immune-based diseases with acute outbreaks in the past 12 months, despite
immunosuppressive treatment

- Severe ischemia-reperfusion injury of current renal transplant with delayed graft
function objectively evident at more than 20 days after transplant AND/OR kidney
transplanted from a deceased, very elderly donor (>80 years)

- Double transplant (renal + another organ)

- HIV, HBV, HCV infection or other severe infectious diseases that prevent blood samples
from being processed in a conventional laboratory

- Chronic Allograft Injury (CAI) unlikely related to immune processes, by the
Investigator´s judgement

- Recurrent primary kidney disease