Background: Graft and patient survival are mainly determined by rejections and infectious complications in transplant recipients. Subclinical graft rejection (SGR) is defined histologically as acute rejection characterized by tubule-interstitial infiltration of the renal allograft without clinical deterioration. SGR is not always studied.
Torque Teno Virus (TTV) is a highly prevalent, nonpathogenic DNA virus. TTV viral load is proposed as a biomarker of immunosuppression in transplant patients.
Objectives: 1- to determine SGR frequency up to 15 months post-transplantation; 2- to determine the association between SGR and TTV viral load in renal transplant patients.
Methods: A prospective cohort study on adult renal transplant recipients, transplanted from November 2018 up to date is being conducted at CEMIC University Hospital, Argentina.
Inclusion criteria: patients with thymoglobulin or basiliximab as induction therapy and tacrolimus, mycophenolic acid and steroids as immunosuppression maintenance.
Exclusion criteria: patients with Belatacep, Sirolimus or Everolimus as immunosuppression maintenance.
Patients were regularly screened for graft rejection (protocol and indication biopsies) and viral infections (CMV viremia or BK viremia).
Protocol biopsies are taken to detect subclinical events at 2 predefined times (3-6 months and 12-15 months). Indication biopsies are taken with renal dysfunction.   
TTV viral load was determined in plasma samples collected before (day -1) and after transplantation (at 1, 3, 6, 9 and 12 months) by real time PCR (R-GENE®).
For determining the association between TTV and SGR, the last sample before the rejection event was analyzed. TTV viral loads from patients with SGR and patients without graft rejection or viral infections (control group) were compared. 
Results: A total of 107 patients were enrolled from November 2018-April 2021. From them, 92 were evaluated; 35 renal biopsies (protocol and indication) and 652 plasma samples were obtained during the studied period. All patients, regardless of their clinical outcome, remained with a functional graft.
Graft rejection (clinical and subclinical) was diagnosed in 28/92 (30%) recipients and 10/92 (10%) recipients had SGF.
All SGR occurred after the 3rd month: 4 between months 3-6; 4 between months 6-9 and 2 between months 12-15.
TTV median viral load between months 6-9 post-transplantation was 2.4 Log10 copies/mL in patients with SGR, compared to 6.0 Log10 copies/mL (R-GENE®) from the control group (p=0.017).
Conclusions: Clinical and subclinical graft rejection occurred in 30% of our cohort. A third of them had SGR.
TTV viral load was consistently lower in patients with SGR compared to control group patients. This difference was statistically significant at 6-9 months post-transplantation.
TTV could be used as an early biomarker to identify patients at higher risk of developing SGR.