Kidney Transplant; ComplicationsDARENCT06130046
MR-proADM as a Early Biomarker for DGF and AR in Kidney and Liver Transplantation
An observational study of Kidney Transplant; Complications and Liver Transplant; Complications, run by University of Rome Tor Vergata at 1 site in Italy.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Kidney Transplant; Complications, Liver Transplant; Complications
- What is being tested?
- MR-proADM dosage
- How many people
- 300 participants
- Where
- 1 siteItaly
- Study dates
- 1 Dec 2022to 1 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Who may be able to join
- Kidney transplant recipient at our Institution
- Liver transplant recipient at our Institution
Who cannot join
- Re-transplantation
- Dual kidney transplantation
- Combined transplant (kidney-liver, kidney-pancreas)
- Autoimmune disease as indication to transplant
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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.
Read the 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.
- Being tested
- MR-proADM dosage
- Keywords
- MR-proADM, Adrenomedullin, Kidney Transplantation, Liver Transplantation, DGF, Acute rejection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MR-proADM dosageBiological
Dosage of MR proADM at OLT/KT, 1, 3, 5, 15 POD and 1, 3, 6, 9, 12 months F-U
| Study group | Role | What they receive |
|---|---|---|
| OLT | 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. Receives: Biological: MR-proADM dosage | |
| KT | 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. Receives: Biological: MR-proADM dosage |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 3 years
Secondary outcomes (4)
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.
Measured: 3 years
Algorithm for risk prediction
Development of a software algorithm predicting the risk of post-transplant complications
Measured: 3 years
Digital Pathology Dataset
Development of digital pathology for graft biopsy
Measured: 3 years
MR-proADM Online Dataset
Development of an online platform to collect and correlate data on post-transplant biopsy and MRPro-ADM levels.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start1 Dec 2022
- Primary completion1 May 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Kidney Transplant; ComplicationsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Rome Tor Vergata
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roberta Angelico, University of Rome Tor Vergata
- Investigators
- Roberta Angelico, PhD FEBS, Principal investigator, University of Rome Tor Vergata
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06130046
- Sponsor's protocol ID
- DARE
- Acronym
- DARE
- Status last verified
- Jul 2025
- First submitted
- 12 Oct 2023
- Last updated
- 1 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Legramante JM, Mastropasqua M, Susi B, Porzio O, Mazza M, Miranda Agrippino G, D Agostini C, Brandi A, Giovagnoli G, Di Lecce VN, Bernardini S, Minieri M. Prognostic performance of MR-pro-adrenomedullin in patients with community acquired pneumonia in the Emergency Department compared to clinical severity scores PSI and CURB. PLoS One. 2017 Nov 21;12(11):e0187702. doi: 10.1371/journal.pone.0187702. eCollection 2017.
PubMed 29161297Minieri M, Di Lecce VN, Lia MS, Maurici M, Bernardini S, Legramante JM. Role of MR-proADM in the risk stratification of COVID-19 patients assessed at the triage of the Emergency Department. Crit Care. 2021 Nov 26;25(1):407. doi: 10.1186/s13054-021-03834-9. No abstract available.
PubMed 34836547Manzia TM, Lai Q, Hartog H, Aijtink V, Pellicciaro M, Angelico R, Gazia C, Polak WG, Rossi M, Tisone G. Graft weight integration in the early allograft dysfunction formula improves the prediction of early graft loss after liver transplantation. Updates Surg. 2022 Aug;74(4):1307-1316. doi: 10.1007/s13304-022-01270-0. Epub 2022 Mar 19.
PubMed 35306614Angelico R, Gerlach UA, Gunson BK, Neil D, Mergental H, Isaac J, Muiesan P, Mirza D, Perera MTP. Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation. Transplantation. 2018 Aug;102(8):1307-1315. doi: 10.1097/TP.0000000000002139.
PubMed 29470351Marutsuka K, Nawa Y, Asada Y, Hara S, Kitamura K, Eto T, Sumiyoshi A. Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in human colonic epithelia and exert an antimicrobial effect. Exp Physiol. 2001 Sep;86(5):543-5. doi: 10.1113/eph8602250.
PubMed 11571480Minamino N, Kikumoto K, Isumi Y. Regulation of adrenomedullin expression and release. Microsc Res Tech. 2002 Apr 1;57(1):28-39. doi: 10.1002/jemt.10048.
PubMed 11921354Kita T, Kitamura K. Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases. Hypertens Res. 2022 Mar;45(3):389-400. doi: 10.1038/s41440-021-00806-y. Epub 2022 Jan 6.
PubMed 34992239Ueda S, Nishio K, Minamino N, Kubo A, Akai Y, Kangawa K, Matsuo H, Fujimura Y, Yoshioka A, Masui K, Doi N, Murao Y, Miyamoto S. Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. Am J Respir Crit Care Med. 1999 Jul;160(1):132-6. doi: 10.1164/ajrccm.160.1.9810006.
PubMed 10390390Eto T, Kitamura K. Adrenomedullin and its role in renal diseases. Nephron. 2001 Oct;89(2):121-34. doi: 10.1159/000046059. No abstract available.
PubMed 11549894Suzuki Y, Itoh H, Katagiri F, Sato F, Kawasaki K, Sato Y, Sato Y, Mimata H, Takeyama M. Relationship between plasma mid-regional pro-adrenomedullin level and resistance to antihypertensive therapy in stable kidney transplant recipients. Peptides. 2013 Oct;48:45-8. doi: 10.1016/j.peptides.2013.08.001. Epub 2013 Aug 13.
PubMed 23954711Reuken PA, Kiehntopf M, Stallmach A, Bruns T. Mid-regional pro-adrenomedullin (MR-proADM): an even better prognostic biomarker than C-reactive protein to predict short-term survival in patients with decompensated cirrhosis at risk of infection? J Hepatol. 2012 Nov;57(5):1156-8; author reply 1158-9. doi: 10.1016/j.jhep.2012.06.036. Epub 2012 Aug 11. No abstract available.
PubMed 22892248Valenzuela-Sanchez F, Valenzuela-Mendez B, Rodriguez-Gutierrez JF, Estella-Garcia A, Gonzalez-Garcia MA. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure. Ann Transl Med. 2016 Sep;4(17):329. doi: 10.21037/atm.2016.08.65.
PubMed 27713887
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MR-proADM as a Early Biomarker for DGF and AR in Kidney and Liver Transplantation
- ClinicalTrials.gov ID
- NCT06130046
- Acronym / sponsor ID
- DARE / DARE
- Keywords
- MR-proADM, Adrenomedullin, Kidney Transplantation, Liver Transplantation, DGF, Acute rejection
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- University of Rome Tor VergataUniversity, hospital or other
- Study start
- 1 Dec 2022 (actual)
- Primary completion
- 1 May 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 13 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| OLT | – | Biological: MR-proADM dosageObservation 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. |
| KT | – | Biological: MR-proADM dosageObservation 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (2 listed)
- Kidney transplant recipient at our Institution
- Liver transplant recipient at our Institution
Key exclusion criteria (4 listed)
- Re-transplantation
- Dual kidney transplantation
- Combined transplant (kidney-liver, kidney-pancreas)
- Autoimmune disease as indication to transplant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MR-proADM dosageDosage of MR proADM at OLT/KT, 1, 3, 5, 15 POD and 1, 3, 6, 9, 12 months F-U | Biological | KT, OLT |
Primary outcome
Accuracy of MR-proADM as biomarker of DGF and AR in OLT/KT
Time frame: 3 years
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.
4 secondary outcomes
Accuracy of MR-proAMD for early detection of other complications in OLT/KT
Time frame: 3 years
Algorithm for risk prediction
Time frame: 3 years
Digital Pathology Dataset
Time frame: 3 years
MR-proADM Online Dataset
Time frame: 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2025.
- Background: PubMed 29161297Legramante JM, Mastropasqua M, Susi B, Porzio O, Mazza M, Miranda Agrippino G, D Agostini C, Brandi A, Giovagnoli G, Di Lecce VN, Bernardini S, Minieri M. Prognostic performance of MR-pro-adrenomedullin in patients with community acquired pneumonia in the Emergency Department compared to clinical severity scores PSI and CURB. PLoS One. 2017 Nov 21;12(11):e0187702. doi: 10.1371/journal.pone.0187702. eCollection 2017.
- Background: PubMed 34836547Minieri M, Di Lecce VN, Lia MS, Maurici M, Bernardini S, Legramante JM. Role of MR-proADM in the risk stratification of COVID-19 patients assessed at the triage of the Emergency Department. Crit Care. 2021 Nov 26;25(1):407. doi: 10.1186/s13054-021-03834-9. No abstract available.
- Background: PubMed 35306614Manzia TM, Lai Q, Hartog H, Aijtink V, Pellicciaro M, Angelico R, Gazia C, Polak WG, Rossi M, Tisone G. Graft weight integration in the early allograft dysfunction formula improves the prediction of early graft loss after liver transplantation. Updates Surg. 2022 Aug;74(4):1307-1316. doi: 10.1007/s13304-022-01270-0. Epub 2022 Mar 19.
- Background: PubMed 29470351Angelico R, Gerlach UA, Gunson BK, Neil D, Mergental H, Isaac J, Muiesan P, Mirza D, Perera MTP. Severe Unresolved Cholestasis Due to Unknown Etiology Leading to Early Allograft Failure Within the First 3 Months of Liver Transplantation. Transplantation. 2018 Aug;102(8):1307-1315. doi: 10.1097/TP.0000000000002139.
- Background: PubMed 11571480Marutsuka K, Nawa Y, Asada Y, Hara S, Kitamura K, Eto T, Sumiyoshi A. Adrenomedullin and proadrenomudullin N-terminal 20 peptide (PAMP) are present in human colonic epithelia and exert an antimicrobial effect. Exp Physiol. 2001 Sep;86(5):543-5. doi: 10.1113/eph8602250.
- Background: PubMed 11921354Minamino N, Kikumoto K, Isumi Y. Regulation of adrenomedullin expression and release. Microsc Res Tech. 2002 Apr 1;57(1):28-39. doi: 10.1002/jemt.10048.
- Background: PubMed 34992239Kita T, Kitamura K. Translational studies of adrenomedullin and related peptides regarding cardiovascular diseases. Hypertens Res. 2022 Mar;45(3):389-400. doi: 10.1038/s41440-021-00806-y. Epub 2022 Jan 6.
- Background: PubMed 10390390Ueda S, Nishio K, Minamino N, Kubo A, Akai Y, Kangawa K, Matsuo H, Fujimura Y, Yoshioka A, Masui K, Doi N, Murao Y, Miyamoto S. Increased plasma levels of adrenomedullin in patients with systemic inflammatory response syndrome. Am J Respir Crit Care Med. 1999 Jul;160(1):132-6. doi: 10.1164/ajrccm.160.1.9810006.
- Background: PubMed 11549894Eto T, Kitamura K. Adrenomedullin and its role in renal diseases. Nephron. 2001 Oct;89(2):121-34. doi: 10.1159/000046059. No abstract available.
- Background: PubMed 23954711Suzuki Y, Itoh H, Katagiri F, Sato F, Kawasaki K, Sato Y, Sato Y, Mimata H, Takeyama M. Relationship between plasma mid-regional pro-adrenomedullin level and resistance to antihypertensive therapy in stable kidney transplant recipients. Peptides. 2013 Oct;48:45-8. doi: 10.1016/j.peptides.2013.08.001. Epub 2013 Aug 13.
- Background: PubMed 22892248Reuken PA, Kiehntopf M, Stallmach A, Bruns T. Mid-regional pro-adrenomedullin (MR-proADM): an even better prognostic biomarker than C-reactive protein to predict short-term survival in patients with decompensated cirrhosis at risk of infection? J Hepatol. 2012 Nov;57(5):1156-8; author reply 1158-9. doi: 10.1016/j.jhep.2012.06.036. Epub 2012 Aug 11. No abstract available.
- Background: PubMed 27713887Valenzuela-Sanchez F, Valenzuela-Mendez B, Rodriguez-Gutierrez JF, Estella-Garcia A, Gonzalez-Garcia MA. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure. Ann Transl Med. 2016 Sep;4(17):329. doi: 10.21037/atm.2016.08.65.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Roberta Angelico, PhD FEBS principal investigator
University of Rome Tor Vergata
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Kidney Transplant; Complications and Liver Transplant; Complications, run by University of Rome Tor Vergata at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Roberta Angelico, PhD FEBS (0620908294, roberta.angelico@med.uniroma2.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Accuracy of MR-proADM as biomarker of DGF and AR in OLT/KT (time frame: 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06130046, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2025; AzTrials last refreshed its copy on 26 Oct 2026.