Systemic Activation of Inflammasomes and Frailty in Older Candidates to Kidney Transplantation

ConditionsChronic Kidney Failure Frailty Aging Inflammation

Trial statusNot yet recruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age70+

SponsorUniversity Hospital, Bordeaux

About this trial

Kidney transplantation (KT) benefit-risk ratio assessment is a challenge in a growing population of older patients with end-stage kidney disease. A pre-KT frailty phenotype has been found predictive of post-KT complications, but biological mechanisms of frailty are poorly known is these patients. Frailty is associated with chronic low-grade inflammation in the older general population, possibly through the inflammasome pathway. Our main objective is to assess if systemic activation of inflammasomes is associated with frailty in older candidates to KT.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥ 70

Patient candidate to kidney transplantation (during assessment for inscription on the waiting-list, or during waiting time after effective inscription), without absolute contraindication

Free, informed and written consent signed by the participant and the investigator (at the latest, on the day of inclusion and before any examination required by the research).

Person affiliated or beneficiary of a social security scheme

Disqualifiers

Inclusion in an industrial study refusing co-inclusion in our study

Person under guardianship, assisted decision-making or under temporary guardianship

Trial design

Design model

Parallel

Treatments tested in this trial

Blood sample
Biological/Vaccine
* Immunophenotyping of peripheral lymphocytes, with a focus on proportions of naïve / central memory / effector memory / TEMRA cells, and markers of activation and senescence * Serum inflammatory markers : CRP, IL-6, MCP-1, TNF, sTNFR1 * Single Molecule Array for IL1 and LUMINEX for IL18 in patient's sera * RT-qPCR for inflammasomes genes (NLRP3, NLRC4, NLRC5, AIM2, ASC, casp1, IL1b, IL18) expression among peripheral blood mononuclear cells * Assembly of the inflammasome platform will be measured in monocytes using intra-cellular staining of the ASC protein and flow cytometry
Geriatric assessment standardized
Behavioral
* Exhaustion (2 standardized questions) * Physical activity \<383 kcal/week (men) or \<270 kcal/week (women), measured using a standardized questionnaire (IPAQ) * 4-meters gait speed, with sex and height-specific cutoffs * Handgrip strength, measured using a dynamometer, with sex and BMI-sp Comorbidity (CIRS-G score ) * Screening for intrinsic capacity decline (first step of ICOPE program, adapted to the study, ) * Physical performance (SPPB score ) * Cognitive functions (MoCA score ), * Depression (GDS-15 score ), * Nutrition (MNA score ) * Sensory functions (Snellen test for vision, HHIES questionnaire for hearing) -- Dependency in activities of daily living (ADL and IADL scores)

Treatment groups

60 Participants

are divided into 2 treatment groups

Group A: Frail PatientsActive comparator 2 interventions

Group B: non frail patientsActive comparator 2 interventions

Trial outcomes