The association of torque teno viral (TTV) load with acute rejection and viral infections in the first-year post renal transplantation
Natalia Boccia1, Noelia S. Reyes2, Gustavo Laham1, Gonzalo Garcia1, Carmen Ricarte3, Raquel Jara3, Eliana Hermida3, Gervasio Soler Pujol1, Carlos Diaz1, G. Caraballal2, Marcela Echavarria2.
1Nephrology section, CEMIC University Hospital, Ciudad Autonoma de Buenos Aires, Argentina; 2Virology Unit (CEMIC‐CONICET), Centro de Educación Médica e Investigaciones Clínicas University Hospital (CEMIC), Villa Mitre, Argentina; 3Virology Laboratory, Centro de Educación Médica e Investigaciones Clínicas University Hospital (CEMIC), Villa Mitre, Argentina
Introduction: Graft survival after renal transplantation (RT) is mainly determined by rejections and infectious complications among others. The individual immune response to the dose of immunosuppressant is highly variable as trough levels are hampered by absorption and metabolism of drugs, and also non-modifiable factors such as age and associated comorbidities that can affect immunity. The non-enveloped DNA non-pathogenic and ubiquitous torque teno virus (TTV) has been postulated as a surrogate marker of immunosuppression in transplant patients. The aim of this study was to evaluate TTV replication as a marker for the appearance of acute rejections or viral infections such as cytomegalovirus (CMV) or BK virus (BKV) after RT.
Methods: This single-center prospective study at CEMIC University Hospital Buenos Aires, Argentina, included 64 patients followed during the first year after transplantation. TTV was detected by real time PCR using primers that amplify a highly conserved region of the 5´non-coding region from all TTV species (Maggi et al., 2003). TTV viral load was quantified on days 0, 3, 7, 14, 21, 30, 90, 180, 360 post-transplantations. Demographics data, clinical and subclinical acute rejection episodes and viral infections (CMV and BKV) detected during the follow-up period were recorded.
Results: The median age was 49.7 years old and 60.3 % were male. Fifty-two patients received a graft from a deceased donor, 98.4 % received thymoglobulin as induction, all patients were on steroids, tacrolimus and mycophenolic acid for maintenance immunosuppression. There were no graft losses and one patient died with a functioning graft within a year after transplantation. TTV was positive in 48/64 (75 %) of patients before transplantation. The median viral load was 2.6 (0.3-3.4) Log10 copies/mL. TTV levels increased rapidly after transplantation. Median viral load +7, +30, +90, +180, and +365 days after transplantation was 3.1, 4.4, 6.5, 5.5 and 5.1 Log10 copies/mL, respectively (p<0.000). On day 90, the prevalence of TTV was 95 %. There was no correlation between Tacrolimus trough levels and TTV throughout the study. During the first-year post-transplantation, 29.7 %, 34.4 %, and 39.7 % had acute rejection, CMV infection, and urine positive BKV, respectively. A total of 15/64 (23.4%) patients presented acute rejection between 3 and 12 months. TTV levels at 6 moths were significantly lower in those patients who rejected compared to those who did not, 4.4 vs. 5.9 Log10 copies/mL (p<0.010). Same trend was observed at 12 months, 4.4 vs. 5.3 Log10 copies/mL but without reaching statistical significance (Figure 1).
On day +90, TTV median viral load was higher in those patients with BKV infection compared to patients without infection (7.06 vs 6.42 Log10 copies/mL, respectively) (Figure 2). Similar results were found at day +90 in patients with CMV infection and without infection (6.69 and 6.37 Log10 copies/mL, respectively) (Figure 3). These differences were not statistically significant.
Conclusions: TTV replication increased after RT, reaching the pick on day +90. We found in this serial quantification a lower viral load at day 180 in patients who presented an acute rejection between 3-to-12-month post transplantation. An association of TTV viral load with viral infections during the first year after RT was observed, although not statistically significant. A higher number of patients are being enrolled for evaluation.
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