Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
| |
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MR-proADM dosage | Biological | Dosage of MR proADM at OLT/KT, 1, 3, 5, 15 POD and 1, 3, 6, 9, 12 months F-U |
|
| 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 |
| 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 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
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
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Roberta Angelico, PhD FEBS | Contact | 0620908294 | roberta.angelico@med.uniroma2.it | |
| Domiziana Pedini, MD | Contact | +393488869569 | domiziana.pedini@libero.it |
| Name | Affiliation | Role |
|---|---|---|
| Roberta Angelico, PhD FEBS | University of Rome Tor Vergata | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Rome Tor Vergata | Recruiting | Rome | 00133 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29161297 | Background | 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. | |
| 34836547 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
EDTA Blood Samples
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 |
| Background |
| Minieri 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. |
| 35306614 | Background | Manzia 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. |
| 29470351 | Background | Angelico 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. |
| 11571480 | Background | Marutsuka 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. |
| 11921354 | Background | Minamino 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. |
| 34992239 | Background | Kita 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. |
| 10390390 | Background | Ueda 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. |
| 11549894 | Background | Eto T, Kitamura K. Adrenomedullin and its role in renal diseases. Nephron. 2001 Oct;89(2):121-34. doi: 10.1159/000046059. No abstract available. |
| 23954711 | Background | Suzuki 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. |
| 22892248 | Background | Reuken 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. |
| 27713887 | Background | Valenzuela-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. |