VOCs in Kidney and Liver Transplants

Exhaled Volatile Organic Compounds as Potential Predictive Biomarkers of Chronic Kidney and Liver Rejection After Transplants

Kidney and liver trasplants represent very challenging lifesaving and effective surgical procedures for patients with end-stage kidney and/or liver disease.

Chronic rejection may occur in 3 to 17% livers transplants and in 20 to 40% kidney transplants.

While acute rejection is clearly detected due to the clinical features and laboratory tools, the early identification of chronic rejection is still challenging since the clinical features are often silents and laboratory tests become suggestive when the damage due to the rejection is almost irreversible.

Considering the recent application of the breathomic to liver and kidney disease and the difficulty in the early detection of chronic rejection after liver and kidney transplants, the analysis of the exhaled VOCs pattern could help early detection of chronic rejection allowing a prompt medical treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Kidney Transplant; Complications; Liver Transplant Rejection
• Intervention / Treatment: Other: Breath analysis

Detailed Description

Kidney and liver trasplants represent very challenging lifesaving and effective surgical procedures for patients with end-stage kidney and/or liver disease.

Nowadays the short and long term success rate of kidney and liver trasplants is pretty hight. Nevertheless, transplant rejection remains one of the biggest limitations with a strong impact on patients survival.

Usually acute rejection occurs within 3 months after the transplant and is the most common cause of transplant failure and the most common indication for re-transplantation .

Chronic rejection may occur in 3 to 17% livers transplants and in 20 to 40% kidney transplants.

While acute rejection is clearly detected due to the clinical features and laboratory tools, the early identification of chronic rejection is still challenging since the clinical features are often silents and laboratory tests become suggestive when the damage due to the rejection is almost irreversible.

Chronic renal transplant rejection is the result of a gradual decrease in the kidney function that starts to become evident three months after surgery.

Kidney chronic rejection is, by definition, immune-mediated and generally divides into chronic active antibody-mediated rejection and chronic active T cell-mediated rejection.

Transplant vasculopathy is the single most important feature of chronic renal transplant rejection and it is the direct consequence of an immune reaction that activates a cytokines cascade with a tissue fibrosis and chronic rejection.

Hypertension and proteinuria are the most important features of declining renal function.

Laboratory tests such as serum creatinine and estimated glomerular filtration rate (eGFR)ccan help to early identify kidney allograft dysfunction. The eGFR is suggested to be a more accurate indicator and predictor of graft function and long term graft loss.

However, a biopsy is mandatory for diagnosing chronic renal transplant rejection. C4d complement fragment deposition in the peritubular capillaries represents the marker for antibody-mediated tissue injury.

Although the incidence of acute and chronic rejection has declined with improvement of immunosuppression regimens, chronic rejection may lead to re-transplant or death.

Chronic liver allograft rejection usually occurs more than 2 months after transplantation and most frequently develops after an unresolved or multiple episodes of acute rejection or indolently over a period of months to years, with few or no clinically apparent acute cellular rejection episodes.

Chronic rejection characterized primarily by fibrointimal hyperplasia of arteries, or obliterative arteriopathy, interstitial fibrosis and atrophy of parenchymal elements.

Often the only reliable early indicator of chronic rejection is persistent and preferential elevation of γ-glutamyl transpeptidase and alkaline phosphatase, which is related to bile duct damage. In most of cases the only clinical sign is jaundice and it appears when allograft dysfunction becomes. Biliary sludging or appearance of biliary strictures, hepatic infarcts, and finally loss of hepatic synthetic function, which can manifest as coagulopathy, malnutrition, and hepatosplenomegaly are late findings presaging allograft failure. Biopsy is mandatory to assess the liver damage.

Breath analysis (Breathomics) is applied widely nowadays in clinical setting in order to identify and evaluate exhaled molecular volatile compounds as expression of a metabolic derangement of the organism including chronic diseases and cancer disease.

A novel approach, a breath test based on the metabolomic evaluation of the volatile organic compounds (VOCs) in the exhaled breath, has recently been developed by our group to identify patients with Colorectal cancer, showing good reliability and compliance.

VOCs analysis has also been demonstrated to find an application in the diagnosis of chronic liver and kidney disease with high sensitivity and specificity.

Considering the recent application of the breathomic to liver and kidney disease and the difficulty in the early detection of chronic rejection after liver and kidney transplants, the analysis of the exhaled VOCs pattern could help early detection of chronic rejection allowing a prompt medical treatment.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • Dept of Emergency and Organ transplantation
    • Contact: Arcangelo F Picciariello, MD; Phone Number: 00393492185104; Email: arcangelopicciariello@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both sex
• Patients eligible for liver or kidney transplant
• Written informed consent

Exclusion Criteria:

• Acute liver failure
• Acute liver and kidney rejection
• HCC
• Re-transplant
• Pregnancy
• IBD
• Any psychiatric disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Liver/kidney transplant; The breath of patients undergoing liver or kidney transplant will be sampled and analysed	Other: Breath analysis; The breath of patients undergoing liver or kidney transplant will be sampled and volatile organic compounds will be identified

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volatile organic compounds in end stage liver disease	to evaluate the pattern of volatile organic compounds in patients elegible for liver transplant	30 days
Volatile organic compounds in end stage kidney disease	to evaluate the pattern of volatile organic compounds in patients elegible for kidney transplant	30 days
Volatile organic compounds after liver transplant	to evaluate the pattern of volatile organic compounds able to identify the onset of chronic failure/rejection after liver transplants	1 year
Volatile organic compounds after liver transplant	to evaluate the pattern of volatile organic compounds able to identify the onset of chronic failure/rejection after kidney transplants	1 year

Collaborators and Investigators

• Sponsor: Societa Italiana di Chirurgia ColoRettale

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 2, 2021
• Primary Completion (ANTICIPATED): October 2, 2022
• Study Completion (ANTICIPATED): March 2, 2023

Study Registration Dates

• First Submitted: August 12, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (ACTUAL): August 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 20, 2021
• Last Update Submitted That Met QC Criteria: April 17, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 38/2020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No