Immune Monitoring of Prevalent Kidney Transplant Recipients Using Torque Teno Virus: A Single-Center, Prospective Cohort Study

Active, not recruiting

• Conditions: Kidney Transplant Infection; Kidney Transplant Rejection; Kidney Transplant; Complications

• Registration Number: NCT05836636
• Lead Sponsor: Singapore General Hospital

Brief Summary

Kidney transplant recipients (KTRs) suffer from immunosuppression-related adverse events (iRAEs), such as infections and malignancy from chronic immunosuppression exposure but are also at risk of graft loss from rejection with under-immunosuppression. Biomarkers that predict both iRAEs and rejection and allow individualisation of immunosuppression exposure are lacking. While plasma viral DNA levels of Torque Teno Virus (TTV), a widely prevalent, non-pathogenic virus, have been shown to predict both iRAE and rejection in incident KTRs within 1 year after transplant, its role for prevalent KTRs on stable immunosuppression is unclear.

The investigators hypothesise that plasma TTV levels can predict iRAEs and rejection in KTRs on stable immunosuppression and propose a pilot study to pursue three specific aims: (1) To determine the TTV levels and its relationship with clinical factors affecting the 'net state of immunosuppression' in prevalent KTRs. (2) To analyse the prognostic value of TTV levels for iRAEs and rejection in prevalent KTRs. (3) To compare the prognostic performance of TTV levels to commonly available biomarkers and composite prognostic scores.

The investigators seek pursue these aims by performing a single-centre, prospective, observational cohort study of 172 KTRs on stable immunosuppression for more than 3 months. TTV levels will be measured, using the TTV R-GENE® kit, upon recruitment and when kidney allograft biopsies are performed. Subjects will be monitored for iRAEs and rejection for at least 12 months.

The study will provide data on the distribution of TTV levels in a prevalent cohort of KTRs and analyse its relationship with clinical factors and important clinical outcomes. If the study indicates that TTV may be predictive of iRAEs and rejection, the investigators aim to conduct further studies including interventional studies using TTV levels to guide immunosuppression. Ultimately, the investigators aim to use TTV as a biomarker to optimise long-term immunosuppression exposure, reduce the risk of iRAEs without increase in rejection, and improve long-term outcomes for KTRs.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-04-19
• Study First Submitted QC: 2023-04-19
• Study First Posted: 2023-05-01
• Study Start: 2023-06-27
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Primary Completion: 2025-07-31
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 172

Inclusion Criteria

• Kidney transplant recipients on follow up at Singapore General Hospital (SGH)
• More than 21 years old
• On stable doses of immunosuppression for more than 3 months

Exclusion Criteria

• Titration of immunosuppression (e.g. for rejection or infection) less than 3 months ago
• Active infection requiring treatment
• Less than 21 years old
• Unable to provide informed consent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Severe infections defined as any infection requiring hospitalization	1 year	Any infection requiring hospitalization

Secondary Outcome Measures

Name	Time	Method
Glomerulonephritis - de novo or recurrent (biopsy-proven)	1 year
Opportunistic infections	1 year	intracellular bacteria, mycobacteria, Listeria monocytogenes, and Nocardia spp., herpesviruses (CMV, HSV, and VZV), polyomaviruses, yeasts (Candida and Cryptococcus), molds (invasive aspergillosis and mucormycosis), and parasites (Toxoplasma gondii, PJP, and Leishmania)
De novo malignancy	1 year	De novo malignancy
Graft loss	1 year	Censored and non-censored for death
Immunosuppression-related adverse event	1 year	Composite outcome of severe infections defined as any infection requiring hospitalization, opportunistic infections, de novo malignancy and calcineurin inhibitor nephrotoxicity
Calcineurin inhibitor nephrotoxicity (biopsy-proven)	1 year	Calcineurin inhibitor nephrotoxicity (biopsy-proven)
Rejection (biopsy-proven)	1 year	With and without borderline T cell-mediated rejection
Graft function	1 year	serum creatinine, estimated glomerular filtration rate by the CKD-EPI equation and urine protein-to-creatinine ratio
Mortality	1 year	All-cause and cause-specific - i.e., infection, malignancy, cardiovascular, others
Immune-mediated adverse event	1 year	Composite outcome of rejection (biopsy-proven) and glomerulonephritis (biopsy-proven)

Trial Locations

Locations (1)

Singapore General Hospital; 🇸🇬 Singapore, Singapore