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Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients.

ABSTRACT: Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured using PCR in stable kidney transplant recipients at ≥1 year after transplantation, and smoking status and alcohol intake were assessed through questionnaires and measurements of urinary cotinine and ethyl glucuronide. A total of 666 KTRs were included (57% male). A total of 549 KTR (82%) had a detectable TTV load (3.1 ± 1.5 log₁₀ copies/mL). In KTR with a detectable TTV load, cyclosporin and tacrolimus use were positively associated with TTV load (St. β = 0.46, p < 0.001 and St. β = 0.66, p < 0.001, respectively), independently of adjustment for potential confounders. Current smoking and alcohol intake of >20 g/day were negatively associated with TTV load (St. β = -0.40, p = 0.004 and St. β = -0.33, p = 0.009, respectively), independently of each other and of adjustment for age, sex, kidney function, time since transplantation and calcineurin inhibitor use. This strong association of smoking and alcohol intake with TTV suggests a need to account for the smoking status and alcohol intake when applying TTV guided immunosuppression in KTR.

SUBMITTER: Doorenbos CSE

PROVIDER: S-EPMC10748022 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients.

Doorenbos Caecilia S E CSE Jonker Jip J Hao Jiasi J Gore Edmund J EJ Kremer Daan D Knobbe Tim J TJ de Joode Anoek A E AAE Sanders Jan Stephan F JSF Thaunat Olivier O Niesters Hubert G M HGM Van Leer-Buter Coretta C CC Bakker Stephan J L SJL

Viruses 20231206 12

Torque Teno Virus (TTV) is a non-pathogenic virus that is highly prevalent among kidney transplant recipients (KTRs). Its circulating load is associated with an immunological status in KTR and is considered a promising tool for guiding immunosuppression. To allow for optimal guidance, it is important to identify other determinants of TTV load. We aimed to investigate the potential association of smoking and alcohol intake with TTV load. For this cross-sectional study, serum TTV load was measured ...[more]

PMID: 38140628

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Project description:Torque teno virus (TTV) is emerging as a potential marker for monitoring immune status. In transplant recipients who are immunosuppressed, higher TTV DNA loads are observed than in healthy individuals. TTV load measurement may aid in optimizing immunosuppressive medication dosing in solid organ transplant recipients. Additionally, there is a growing interest in the role of HDL particles in immune function; therefore, assessment of both HDL concentrations and TTV load may be of interest in transplant recipients. The objective of this study was to analyze TTV loads and HDL parameters in serum samples collected at least one year post-transplantation from 656 stable outpatient kidney transplant recipients (KTRs), enrolled in the TransplantLines Food and Nutrition Cohort (Groningen, the Netherlands). Plasma HDL particles and subfractions were measured using nuclear magnetic resonance spectroscopy. Serum TTV load was measured using a quantitative real-time polymerase chain reaction. Associations between HDL parameters and TTV load were examined using univariable and multivariable linear regression. The median age was 54.6 [IQR: 44.6 to 63.1] years, 43.3% were female, the mean eGFR was 52.5 (±20.6) mL/min/1.73 m2 and the median allograft vintage was 5.4 [IQR: 2.0 to 12.0] years. A total of 539 participants (82.2%) had a detectable TTV load with a mean TTV load of 3.04 (±1.53) log10 copies/mL, the mean total HDL particle concentration was 19.7 (±3.4) μmol/L, and the mean HDL size was 9.1 (±0.5) nm. The univariable linear regression revealed a negative association between total HDL particle concentration and TTV load (st.β = -0.17, 95% CI st.β: -0.26 to -0.09, p < 0.001). An effect modification of smoking behavior influencing the association between HDL particle concentration and TTV load was observed (Pinteraction = 0.024). After adjustment for age, sex, alcohol intake, hemoglobin, eGFR, donor age, allograft vintage and the use of calcineurin inhibitors, the negative association between HDL particle concentration and TTV load remained statistically significant in the non-smoking population (st.β = -0.14, 95% CI st.β: -0.23 to -0.04, p = 0.006). Furthermore, an association between small HDL particle concentration and TTV load was found (st.β = -0.12, 95% CI st.β: -0.22 to -0.02, p = 0.017). Higher HDL particle concentrations were associated with a lower TTV load in kidney transplant recipients, potentially indicative of a higher immune function. Interventional studies are needed to provide causal evidence on the effects of HDL on the immune system.

Project description:Following kidney transplantation, lifelong immunosuppressive therapy is essential to prevent graft rejection. On the downside, immunosuppression increases the risk of severe infections, a major cause of death among kidney transplant recipients (KTRs). To improve post-transplant outcomes, adequate immunosuppressive therapy is therefore a challenging but vital aspect of clinical practice. Torque teno virus load (TTVL) was shown to reflect immune competence in KTRs, with low TTVL linked to an elevated risk for rejections and high TTVL associated with infections in the first year post-transplantation. Yet, little is known about the dynamics of TTVL after the first year following transplantation and how TTVL changes with respect to short-term modifications in immunosuppressive therapy. Therefore, we quantified TTVL in 106 KTRs with 108 clinically indicated biopsies, including 65 biopsies performed >12 months post-transplantation, and correlated TTVL to histopathology. In addition, TTVL was quantified at 7, 30, and 90 days post-biopsy to evaluate how TTVL was affected by changes in immunosuppression resulting from interventions based on histopathological reporting. TTVL was highest in patients biopsied between 1 and 12 months post-transplantation (N = 23, median 2.98 × 107 c/mL) compared with those biopsied within 30 days (N = 20, median 7.35 × 103 c/mL) and > 1 year post-transplantation (N = 65, median 1.41 × 104 c/mL; p < 0.001 for both). Patients with BK virus-associated nephropathy (BKVAN) had significantly higher TTVL than patients with rejection (p < 0.01) or other pathologies (p < 0.001). When converted from mycophenolic acid to a mTOR inhibitor following the diagnosis of BKVAN, TTVL decreased significantly between biopsy and 30 and 90 days post-biopsy (p < 0.01 for both). In KTR with high-dose corticosteroid pulse therapy for rejection, TTVL increased significantly between biopsy and 30 and 90 days post-biopsy (p < 0.05 and p < 0.01, respectively). Of note, no significant changes were seen in TTVL within 7 days of changes in immunosuppressive therapy. Additionally, TTVL varied considerably with time since transplantation and among individuals, with a significant influence of age and BMI on TTVL (p < 0.05 for all). In conclusion, our findings indicate that TTVL reflects changes in immunosuppressive therapy, even in the later stages of post-transplantation. To guide immunosuppressive therapy based on TTVL, one should consider inter- and intraindividual variations, as well as potential confounding factors.

Project description:IntroductionCytomegalovirus (CMV) is the most frequent infectious complication following solid organ transplantation. Torque teno viruses (TTV) viremia has been proposed as a biomarker of functional immunity in the management of kidney transplant recipients (KTR). The QuantiFERON®-CMV (QF-CMV) is a commercially available assay that allows the assessment of CD8+ T-cell responses in routine diagnostic laboratories.MethodsIn a prospective national multicenter cohort of 64 CMV-seropositive (R+) KTR, we analyzed the value of TTV load and the two markers of the QF-CMV assay [QF-Ag (CMV-specific T-cell responses) and QF-Mg (overall T-cell responses)], alone and in combination, in prediction of CMV reactivation (≥3 log10 IU/ ml) in the first post-transplant year. We compared previously published cut-offs and specific cut-offs optimized from ROC curves for our population.ResultsUsing the conventional cut-off (3.45 log10 copies/ml), TTV load at D0 [inclusion visit on the day of transplantation before induction (D0)], or at M1 (1-month post-transplant visit) perform better in predicting CMV viremia control than CMV reactivation. Survival analyses suggest a better performance of our optimized TTV cut-offs (3.78 log10 copies/ml at D0 and 4.23 log10 copies/ml at M1) for risk stratification of CMV reactivation in our R+ KTR cohort. The QF-CMV (QF-Ag = 0.2 IU/ml, and QF-Mg = 0.5 IU/ml) also appears to better predict CMV viremia control than CMV reactivation. Moreover, survival analyses suggest that the QF-Mg would perform better than the QF-Ag in stratifying the risk of CMV reactivation. The use of our optimized QF-Mg cut-off (1.27 IU/ml) at M1 further improved risk stratification of CMV reactivation. Using conventional cut-offs, the combination of TTV load and QF-Ag or TTV load and QF-Mg did not improve prediction of CMV viremia control compared to separate analysis of each marker but resulted in an increase of positive predictive values. The use of our cut-offs slightly improved risk prediction of CMV reactivation.ConclusionThe combination of TTV load and QF-Ag or TTV load and QF-Mg could be useful in stratifying the risk of CMV reactivation in R+ KTR during the first post-transplant year and thereby have an impact on the duration of prophylaxis in these patients.Clinical trial registrationClinicalTrials.gov registry, identifier NCT02064699.

Dataset Information

Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients.

Publications

Smoking, Alcohol Intake and Torque Teno Virus in Stable Kidney Transplant Recipients.

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