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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Transplant Infection; Kidney Transplant Rejection; Kidney Transplant; Complications
• Intervention / Treatment: Other: Torque teno virus DNA measurement

• Study Type: Observational
• Enrollment (Actual): 172

Contacts and Locations

Study Locations

• Singapore
  • Singapore
    • Singapore, Singapore, Singapore, 767972
      • Singapore General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Kidney transplant recipients (KTRs) on stable doses of immunosuppression for more than 3 months

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severe infections defined as any infection requiring hospitalization	Any infection requiring hospitalization	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opportunistic infections	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)	1 year
De novo malignancy	De novo malignancy	1 year
Calcineurin inhibitor nephrotoxicity (biopsy-proven)	Calcineurin inhibitor nephrotoxicity (biopsy-proven)	1 year
Rejection (biopsy-proven)	With and without borderline T cell-mediated rejection	1 year
Glomerulonephritis - de novo or recurrent (biopsy-proven)		1 year
Graft function	serum creatinine, estimated glomerular filtration rate by the CKD-EPI equation and urine protein-to-creatinine ratio	1 year
Graft loss	Censored and non-censored for death	1 year
Mortality	All-cause and cause-specific - i.e., infection, malignancy, cardiovascular, others	1 year
Immunosuppression-related adverse event	Composite outcome of severe infections defined as any infection requiring hospitalization, opportunistic infections, de novo malignancy and calcineurin inhibitor nephrotoxicity	1 year
Immune-mediated adverse event	Composite outcome of rejection (biopsy-proven) and glomerulonephritis (biopsy-proven)	1 year

Collaborators and Investigators

• Sponsor: Singapore General Hospital

Publications and helpful links

General Publications

• Ho QY, Lai CMD, Liew IT, Oon LLE, Lim KL, Chung SJ, Thangaraju S, Tien SC, Tan CS, Kee T. Immune monitoring of prevalent kidney transplant recipients using Torque Teno Virus: Protocol for a single-centre prospective cohort study. BMJ Open. 2023 Sep 19;13(9):e076122. doi: 10.1136/bmjopen-2023-076122.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2023
• Primary Completion (Actual): July 31, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: April 19, 2023
• First Submitted That Met QC Criteria: April 19, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2023/2170

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No