Clinical trial NCT06887075: Systemic Activation of Inflammasomes and Frailty in Older Candidates to Kidney Transplantation
Official title: Systemic Activation of Inflammasomes and Frailty in Older Candidates to Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Chronic Kidney Failure
Frailty
Aging
Inflammation
Keywords: Older persons
End-stage kidney disease
Kidney transplantation
Immune aging
Chronic low-grade inflammation
Inflammasomes
Frailty
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2025-03-20
Enrollment: 60
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: IL1
timeFrame: at recruitment (up to 30 days)
measure: IL18
timeFrame: at recruitment (up to 30 days)
measure: inflammasomes genes
timeFrame: at recruitment (up to 30 days)
measure: inflammasome platform
timeFrame: at recruitment (up to 30 days)
measure: Weight
timeFrame: at enrollment (Day 0), at recruitment (up to 30 days)
measure: Activity
timeFrame: at enrollment (Day 0), at recruitment (up to 30 days)
measure: Gait
timeFrame: at enrollment (day 0), at recruitment (up to 30 days)
measure: Handgrip strength
timeFrame: at enrollment (day 0), at recruitment (up to 30 days)
Secondary outcomes:
measure: Comorbidity
timeFrame: at recruitment (up to 30 days)
measure: decline
timeFrame: at recruitment (up to 30 days)
measure: Physical performance
timeFrame: at recruitment (up to 30 days)
measure: Cognitive functions
timeFrame: at recruitment (up to 30 days)
measure: Depression
timeFrame: at recruitment (up to 30 days)
measure: Nutrition
timeFrame: at recruitment (up to 30 days)
measure: Snellen test
timeFrame: at recruitment (up to 30 days)
measure: ADL
timeFrame: at recruitment (up to 30 days)
measure: Immunophenotyping
timeFrame: at recruitment (up to 30 days)
measure: CRP
timeFrame: at recruitment (up to 30 days)
measure: IL-6
timeFrame: at recruitment (up to 30 days)
measure: MCP-1
timeFrame: at recruitment (up to 30 days)
measure: TNF
timeFrame: at recruitment (up to 30 days)
measure: sTNFR1
timeFrame: at recruitment (up to 30 days)
measure: HHIES questionnaire
timeFrame: at recruitment (up to 30 days)
measure: IADL
timeFrame: at recruitment (up to 30 days)
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux - Hôpital Pellegrin -
city: Pessac
country: France
facility: CHU de Bordeaux, Hôpital Xavier Arnozan- Gérontologie Clinique
city: Toulouse
country: France
facility: CHU de Toulouse - Hôpital Rangueil
Study officials:
affiliation: University Hospital, Bordeaux
name: Florent GUERVILLE, MD
role: PRINCIPAL_INVESTIGATOR
References: