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

University Hospital of Bordeaux

Status: Not yet enrolling

Conditions: Aging; Chronic Kidney Failure; Inflammation; Frailty

Treatments: Biological: Blood sample; Behavioral: Geriatric assessment standardized

Study type: Interventional

Funder types: Other

Identifiers

NCT06887075

CHUBX 2022/31

Details and patient eligibility

About

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.

Full description

Kidney transplantation (KT) benefit-risk ratio assessment is a challenge in a growing population of older patients with end-stage kidney disease. Chronic low-grade inflammation is a hallmark of biological aging and is associated with age-related diseases and frailty. Frailty is conceptually defined as an agerelated reduction in physiological reserve increasing vulnerability to stressors. A pre-KT frailty phenotype is associated with post-KT complications, including re-hospitalizations, delayed graft function, delirium and 5-year mortality. Taking pre-KT inflammation into account (serum level of CRP, IL6, sTNFR1) improves prediction of mortality on KT waiting-list, independently of comorbidity.

Molecular and cellular pathways of this inflammation are poorly known, and may involve inflammasomes. Inflammasomes are intra-cellular protein complexes whose assembly, upon stress signals, triggers maturation and release of pro-inflammatory cytokines named interleukine (IL)-1 and IL-18. Inflammasomes are involved in locomotor, cognitive and immune aging in mice, and systemic expression of inflammasomes genes is associated with mortality in older humans. Data is lacking about systemic activation of inflammasomes in older patients with end-stage kidney disease. Our main objective is to assess if pre-KT systemic activation of inflammasomes is associated with frailty in older candidates to KT.

We will measure systemic activation of inflammasomes in peripheral blood of older candidates to KT using cytokine bead-based multiplex assay, Single Molecule Array, intra-cytoplasmic staining, flow cytometry and RT-qPCR in peripheral blood mononuclear cells. Frailty will be measured using validated standardized criteria. A frailty phenotype is defined by at least 3 of the following criteria:

weight loss, exhaustion, muscle weakness, low physical activity, low gait speed.

Enrollment: 60 estimated patients

Sex: All

Ages: 70+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

• Inclusion criteria:

  • 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

• Exclusion criteria:

  • Inclusion in an industrial study refusing co-inclusion in our study
  • Person under guardianship, assisted decision-making or under temporary guardianship

Trial design

Primary purpose: Diagnostic

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Frail Patients

Active Comparator group

Description:

Frailty will be measured clinically using reference criteria in the general population and validated in Kidney Transplantation (KT), i.e. predictive of post-KT complications: delayed recovery of graft function, graft function, early re-hospitalization, occurrence of post-operative confusion, mortality. Fragile patients present at least 3 out of 5 criteria

Treatment:

Behavioral: Geriatric assessment standardized

Biological: Blood sample

non frail patients

Active Comparator group

Description:

Patients will be considered non-fragile if they present 0 to 2 criteria

Treatment:

Behavioral: Geriatric assessment standardized

Biological: Blood sample