MO1022: Torque Teno Virus Load in Kidney Transplantation: Association with Donor and Recipient Characteristics and Clinical Follow-Up Data
Authors: Mayer Katharina , Haupenthal Frederik , Strassl Robert , Schiemann Martin , Doberer Konstantin , Bauernfeind Florian , Naar Luis , Görzer Irene , Puchhammer-Stöckl Elisabeth , Bond Gregor 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The apathogenic and torque teno virus (TTV) is associated with the state of immunosuppression in solid organ transplant recipients. After kidney transplantation, quantification of TTV viral load may serve as a risk stratification tool for allograft rejection and infectious events. Besides a robust and independent association between recipient age, sex and TTV load, respectively, limited data exists on other potential determinants of TTV load. This trial was designed to analyse the association between TTV and detailed recipient and donor baseline characteristics and clinical follow-up parameters.

METHOD
This retrospective analysis included all 386 consecutive adult recipients of a kidney allograft transplanted between 1 January 2016 and 30 June 2018 at the Medical University Vienna from the prospective observational TTV-POET trial (institutional review board approval number: 1785/2016; German Clinical Trials Registry number: DRKS00012335). For the present analysis, we included TTV measures before transplantation (d0), at month 1 (m1), at month 3 (m3) and at month 12 (m12) after transplantation. TTV DNA was extracted from patient plasma and assessed by real-time PCR with laboratory-developed primers. TTV load was associated with recipient and donor baseline characteristics and follow-up data.

RESULTS
The median recipient and donor age at transplantation was 55 years. A total of 135 (35%) kidney allograft recipients were female; 74 patients (19%) had a history of prior kidney transplantation; and 318 patients (82%) received a deceased donor kidney transplant. A total of 34 patients (9%) had pre-formed donor-specific antibodies (DSA); 19 patients (5%) received an AB0-incompatible transplant. For the whole cohort, 1-year patient survival was 95.6% and 1-year death censored graft survival was 94.8%.
Baseline TTV load (d0) was lower in female recipients (P = 0.003) and higher in older recipients {β 0.033, [95% confidence interval (95% CI) 0.002–0.066]; P = 0.039}. Baseline TTV load was not associated with recipient body mass index and a history of immunological causes of end-stage renal disease and diabetes mellitus, respectively. TTV load within the first year after kidney transplantation did not show an association with the prevalence of preformed DSA, induction treatment, AB0-incompatibility and HLA-mismatch, respectively. Our trial detected an association between donor age and TTV load. Recipients from older donors showed higher TTV loads (m1, β 0.037, 95% CI 0.008–0.065, P = .01; m3, β 0.04, 95% CI 0.012–0.068, P = .005; m12, β 0.065, 95% CI 0.028–0.01, P = .001). There was no association between TTV load during the first year after transplantation and donor sex. When investigating the association between TTV load and clinical follow-up data, TTV levels showed a negative correlation with peripheral blood leukocyte and lymphocyte counts during the first year after transplantation [lymphocytes: m1, β –0.867, 95% CI –1.367–0.364, P = .01; m3, β –0.985, 95% CI –1.709–0.260, P = .008; m12, β –1.304, 95% CI –2.156–0.452, P = .003; data on leukocytes not shown). These findings might reflect the role of lymphocytes for TTV control. Additionally, TTV viral load negatively correlated with the estimated glomerular filtration rate (MDRD) within the first year after kidney transplantation (m1, β –0.043, 95% CI –0.066–0.02, P &lt; .001; m3, β –0.024, 95% CI –0.049–0.001, P = .06; m12, β –0.078, 95% CI –0.111–0.045, P &lt; .001). One might speculate that a higher eGFR might be a proxy for a healthier donor being more capable of controlling TTV infection. TTV viral load was associated with tacrolimus trough levels in month 12 after transplantation (β 1.262, 95% CI 0.0221–0.250; P = .019), but not with the amount of mycophenolic acid dosage.

CONCLUSION
This study revealed an association between TTV viral load and distinct baseline donor and recipient characteristics and clinical follow-up data, including kidney function. Further analysis, especially longitudinal assessment of TTV levels, may help to further dissect the interplay between TTV viral load and the state of immunosuppression in patients undergoing kidney transplantation.