Clinical trial NCT06130046: MR-proADM as a Early Biomarker for DGF and AR in Kidney and Liver Transplantation
Official title: MR-proADM as a Early Biomarker for DGF and AR in Kidney and Liver Transplantation
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Kidney Transplant; Complications
Liver Transplant; Complications
Keywords: MR-proADM
Adrenomedullin
Kidney Transplantation
Liver Transplantation
DGF
Acute rejection
Lead sponsor: University of Rome Tor Vergata
Sponsor class: OTHER
First posted: 2023-11-13
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Any adult kidney or liver transplant recipients who underwent OLT or KT at the University of Rome Tor Vergata with no indication for autoimmune diseases or for combined/dual transplant or re-transplantation

Brief summary: To define the sensibility and the specificity of increased levels of MR-proADM for early, non-invasive, diagnosis of AR and DGF after kidney and liver transplantation creating a predictive model for related complications after kidney and liver transplantation based on the pre-operative and post-operative levels of MR-proADM and by a machine learning process.

Detailed description: Despite long-term outcomes of kidney and liver transplantation significantly improved in the last decades, high morbidity and mortality is still an issue at short term after transplantation. Specifically, occurrence of delayed graft function (DGF) and early acute rejection (AR) may cause multi-organ failure or graft failure, admission to intensive care unit, prolonged hospitalization and high-dosage immunosuppressive therapy which might expose patients to several further complications such as infections, neoplasm, and metabolic disease. Consequently, solid organ transplant recipients represent a very frail population at high risk of complications. Therefore, development of new biomarkers for the prevention and early diagnosis of the major post-transplant complications influencing the morbidity and mortality of solid organ transplant recipients are needed. Adrenomedullin (ADM) is a 52-amino acid peptide with a variety of physiologic functions such as immunemodulating activity, direct bactericidal activity, maintenance of renal homeostasis, and vasodilatory activity. Recent study has shown that midregional proADM (MR-proADM) is co-synthesized with ADM in equimolar amounts and has the advantages of a longer half-life, lack of bioactivity and lack of protein binding. MR-proADM has been recognized as a prognostic marker, stratifying the mortality risk in patients with sepsis in intensive care units. Moreover, recently MD-proADM has been also associated with risk of specific organ failure such as acute kidney injury, acute liver damage, acute respiratory distress syndrome and acute cardiac injury. Literature results suggest that recovery of graft function after KT may lead to decrease in plasma MR-proADM level in patients with ESRD, and that plasma MR-proADM level may could increase in the early phases of DGF and AR after KT and LT as a response damage and to the immune activation. The study will allow to evaluate the utility MR-proADM as an early biomarker of DGF and AR in patients undergoing kidney and liver transplantation at our Institution. Also, the study aims to analyze how the value of this biomarker can change in association with post-transplant complication and to create a predicting model by machine cut-off values of references for MR-proADM.

Eligibility criteria: Inclusion Criteria:

* Kidney transplant recipient at our Institution
* Liver transplant recipient at our Institution

Exclusion Criteria:

* Re-transplantation
* Dual kidney transplantation
* Combined transplant (kidney-liver, kidney-pancreas)
* Autoimmune disease as indication to transplant

Primary outcomes:
measure: Accuracy of MR-proADM as biomarker of DGF and AR in OLT/KT
timeFrame: 3 years
Secondary outcomes:
measure: Accuracy of MR-proAMD for early detection of other complications in OLT/KT
timeFrame: 3 years
measure: Algorithm for risk prediction
timeFrame: 3 years
measure: Digital Pathology Dataset
timeFrame: 3 years
measure: MR-proADM Online Dataset
timeFrame: 3 years
Other outcomes:
Locations:
city: Rome
country: Italy
facility: University of Rome Tor Vergata
Study officials:
affiliation: University of Rome Tor Vergata
name: Roberta Angelico, PhD FEBS
role: PRINCIPAL_INVESTIGATOR
References:
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