MR-proADM as a Early Biomarker for DGF and AR in Kidney and Liver Transplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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MR-proADM as a Early Biomarker for DGF and AR in Kidney and Liver Transplantation

Conditions
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Kidney Transplant; Complications, Liver Transplant; Complications

Intervention / Treatment
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* Biological: MR-proADM dosage


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| OLT<br>Observation of MR-proADM levels at protocol timepoints to predict main (DGF and AR) and secondary (surgical complications, infections, others) complications after liver transplantation at our Institution. | Biological: MR-proADM dosage<br>* Dosage of MR proADM at OLT/KT, 1, 3, 5, 15 POD and 1, 3, 6, 9, 12 months F-U<br>|
| KT<br>Observation of MR-proADM levels at protocol timepoints to predict main (DGF and AR) and secondary (surgical complications, urological complications, infections, others) complications after kidney transplantation at our Institution. | Biological: MR-proADM dosage<br>* Dosage of MR proADM at OLT/KT, 1, 3, 5, 15 POD and 1, 3, 6, 9, 12 months F-U<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of MR-proADM as biomarker of DGF and AR in OLT/KT | 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. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy of MR-proAMD for early detection of other complications in OLT/KT | Creating a predictive model of complications after kidney and liver transplantation based on the pre-operative and post-operative levels of MR-proADM by machine learning process. | 3 years | 
| Algorithm for risk prediction | Development of a software algorithm predicting the risk of post-transplant complications | 3 years | 
| Digital Pathology Dataset | Development of digital pathology for graft biopsy | 3 years | 
| MR-proADM Online Dataset | Development of an online platform to collect and correlate data on post-transplant biopsy and MRPro-ADM levels. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MR-proADM, Adrenomedullin, Kidney Transplantation, Liver Transplantation, DGF, Acute rejection