scholarly journals Predictors of CMV Infection in CMV-seropositive Kidney Transplant Recipients: Impact of Pre-transplant CMV-specific Humoral Immunity

2021 ◽  
Author(s):  
Similan Kirisri ◽  
Apirom Vongsakulyanon ◽  
Surasak Kantachuvesiri ◽  
Raymund R Razonable ◽  
Jackrapong Bruminhent
Keyword(s):  
At Risk ◽  
Kidney Transplant ◽  
Humoral Immunity ◽  
Induction Therapy ◽  
Cumulative Incidence ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Ischemic Time ◽  
Cold Ischemic Time

Abstract Introduction Although cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a relatively lower risk of CMV infection than CMV-seronegative recipients who receive allograft from CMV-seropositive donors, some patients remain at risk of CMV infection after transplant. We investigated the pre-transplant CMV-specific humoral immunity (CHI) and other CMV infection predictors in CMV-seropositive kidney transplant (KT) recipients. Methods This retrospective study was conducted on adult CMV-seropositive KT recipients during 2017 and 2018. The cumulative incidence of CMV infection was estimated with Kaplan–Meier methodology. CHI, measured with an enzyme-linked fluorescent immunoassay and other predictors for CMV infection, was analyzed using Cox proportional hazards models. Results Of the 340 CMV-seropositive KT recipients (37% female; age [mean ± SD]: 43±11 years), 69% received deceased-donor allograft and 64% received induction therapy. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%. In multivariate analysis, low pre-transplant CHI (defined as anti-CMV IgG titer <20 AU/ml) was significantly associated with CMV infection (HR, 2.98; 95% CI, 1.31–6.77, [p=0.009]). Other significant predictors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06, [p=0.005]), anti-thymocyte induction therapy (HR, 2.90; 95% CI 1.09–7.74, [p=0.033]), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10, [p=0.002]). Conclusion A low pre-transplant CHI is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. A quantitative anti-CMV IgG assay could potentially stratify CMV-seropositive patients at risk of CMV infection after KT.

scholarly journals 1198. Measurement of Pre-transplant Anti-cytomegalovirus (CMV) Immunoglobulin G Titer to Predict Risk of CMV Infection in CMV-seropositive Kidney Transplant Recipients

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S621-S621
Author(s):  
Similan Kirisri ◽  
Apirom Vongsakulyanon ◽  
Surasak Kantachuvesiri ◽  
Jackrapong Bruminhent
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Immunoglobulin G ◽  
Cumulative Incidence ◽  
Preventive Strategy ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection

Abstract Background Although cytomegalovirus (CMV)-seropositive solid organ transplant recipients have a lower risk of CMV infection compared with CMV-seronegative recipients, some patients remain at risk of CMV infection after transplant. Low pre-transplant anti-CMV immunoglobulin G (IgG) titer has been reported as a predictor of CMV infection in CMV-seropositive liver and heart transplant recipients, but this association in CMV-seropositive kidney transplant (KT) recipients has not been explored. We investigated the pre-transplant anti-CMV IgG titer and other CMV infection risk factors in CMV-seropositive KT recipients. Methods This retrospective study was conducted on CMV-seropositive KT recipients aged >18 years old at Ramathibodi Hospital during 2017 and 2018. The cumulative incidence of CMV infection was estimated with Kaplan–Meier methodology. The pre-transplant anti-CMV IgG titer was measured with an enzyme-linked fluorescent immunoassay. Risk factors for CMV infection were analyzed with Cox proportional hazards models. Results Of the 340 included CMV-seropositive KT recipients (37% female; age [mean±SD]: 43±11 years), 69% and 64% received deceased-donor allograft and induction therapy, respectively. The anti-CMV IgG titer was < 20 and >20 AU/ml in 7.1% and 92.9% of patients, respectively. During a mean follow-up of 14 months, the cumulative incidence of CMV infection was 14.8%, including both asymptomatic CMV infection (69%) and tissue-invasive disease (31%). A pre-transplant anti-CMV IgG titer of < 20 AU/ml was significantly associated with CMV infection in both the univariate analysis (HR, 2.70; 95%CI, 1.21–6.05, [p=0.02]) and the multivariate analysis (HR, 2.98; 95% CI, 1.31–6.77, [p=0.009]). Other significant risk factors of CMV infection included older donor age (HR, 1.03; 95% CI, 1.01–1.06, [p=0.005]), anti-thymocyte induction therapy (HR, 2.90; 95% CI 1.09–7.74, [p=0.033]), and prolonged cold ischemic time (HR, 1.06; 95% CI, 1.02–1.10, [p=0.002]). Conclusion A low pre-transplant CMV-specific humoral immunity is independently associated with post-transplant CMV infection in CMV-seropositive KT recipients. The universally available anti-CMV IgG titer test could potentially stratify those at risk and target preventive strategy appropriately. Disclosures All Authors: No reported disclosures

scholarly journals Impacts of Interleukin-18 Polymorphisms on the Incidence of Delayed-Onset Cytomegalovirus Infection in a Cohort of Kidney Transplant Recipients

2019 ◽  
Vol 6 (9) ◽  
Author(s):  
Isabel Pérez-Flores ◽  
Jose Luis Santiago ◽  
Cristina Fernández-Pérez ◽  
Elena Urcelay ◽  
María Ángeles Moreno de la Higuera ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Cytomegalovirus Infection ◽  
Disease Incidence ◽  
Defense Responses ◽  
Solid Organ ◽  
Nucleotide Polymorphisms ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection ◽  
Delayed Onset

Abstract Background The incidence of cytomegalovirus (CMV) infection in solid organ transplant recipients may be reduced by antiviral prophylaxis, but this strategy may lead to delayed-onset CMV infection. The proinflammatory cytokine interleukin (IL)-18 plays a major role in viral host defense responses. This study examines the impacts of 2 single-nucleotide polymorphisms (SNPs) in the promoter region of the IL-18 gene, -607C/A (rs1946518) and -137G/C (rs187238), on the incidence of delayed-onset CMV infection in patients undergoing kidney transplant. Methods This retrospective study analyzed 2 IL-18 SNPs in consecutive adult kidney transplant recipients using real-time polymerase chain reaction with TaqMan probes. Participants were enrolled over the period 2005–2013 and stratified according to their IL-18 SNP genotype. The concordance index (Harrell’s c-index) was used as a measure of the discriminatory power of the predictive models constructed with bootstrapping to correct for optimistic bias. Results Seven hundred nine patients received transplants in the study period, and 498 met selection criteria. Cytomegalovirus infection and disease incidence were 38% and 7.5%, respectively. In multivariate competing risk regression models, carriers of the -607C/-137G haplotype who received prophylaxis showed a higher incidence of CMV replication after antiviral agent discontinuation (hazard ratio = 2.42 [95% confidence interval, 1.11–5.26]; P = .026), whereas CMV disease was not observed in those given prophylaxis who were noncarriers of this polymorphism (P = .009). Conclusions Our findings suggest that the -607C/-137G IL-18 haplotype is associated with a higher incidence of postprophylaxis CMV replication. The prior identification of this polymorphism could help select alternative measures to prevent delayed-onset CMV infection in these patients.

Kinetic of the CMV-specific T-cell immune response and CMV infection in CMV-seropositive kidney transplant recipients receiving rabbit anti-thymocyte globulin induction therapy: A pilot study

2018 ◽  
Vol 20 (3) ◽  
pp. e12883 ◽  
Author(s):  
Cecilia Martín-Gandul ◽  
Pilar Pérez-Romero ◽  
Damián Mena-Romo ◽  
Alejandro Molina-Ortega ◽  
Francisco M. González-Roncero ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Pilot Study ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Cell Immune Response ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Cmv Infection

Immunosuppressive Management of Pediatric Kidney Transplant Recipients

2020 ◽  
Vol 26 (28) ◽  
pp. 3451-3459
Author(s):  
Tomáš Seeman
Keyword(s):  
Immunosuppressive Therapy ◽  
Kidney Transplant ◽  
Induction Therapy ◽  
Graft Loss ◽  
Calcineurin Inhibitors ◽  
Mtor Inhibitors ◽  
Therapeutic Drug ◽  
High Dose ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients

: Kidney transplantation is a preferable treatment of children with end-stage kidney disease. All kidney transplant recipients, including pediatric need immunosuppressive medications to prevent rejection episodes and graft loss. : Induction therapy is used temporarily only immediately following transplantation while maintenance immunosuppressive drugs are started and given long-term. There is currently no consensus regarding the use of induction therapy in children; its use should be decided based on the immunological risk of the child. : The recent progress shows that the recommended strategy is to use as maintenance immunosuppressive therapy a combination of a calcineurin inhibitor (preferably tacrolimus) with an antiproliferative drug (preferably mycophenolate mofetil) with steroids that can be withdrawn early or late in low-risk children. The mTOR-inhibitors (sirolimus, everolimus) are used rarely in pediatrics because of common side effects and no evidence of a benefit over calcineurin inhibitors. The use of calcineurin inhibitors, mycophenolate, and mTOR-inhibitors should be followed by therapeutic drug monitoring. : Immunosuppressive therapy of acute rejection consists of high-dose steroids and/or anti-lymphocyte antibodies (T-cell mediated rejection) or plasma exchange, intravenous immunoglobulines and/or rituximab (antibodymediated rejection). : The future strategies for research are mainly precise characterisation of children needing induction therapy, more specific indications for mTOR-inhibitors and for the far future, the possibility to reach the immuno tolerance.

Cytomegalovirus in Solid Organ Transplant Recipients: Clinical Updates, Challenges and Future Directions

2020 ◽  
Vol 26 (28) ◽  
pp. 3497-3506
Author(s):  
Raymund R. Razonable
Keyword(s):  
Organ Transplantation ◽  
Solid Organ Transplantation ◽  
Organ Transplant ◽  
Solid Organ Transplant ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Future Directions ◽  
Prevention And Treatment ◽  
Solid Organ Transplant Recipients

Cytomegalovirus is the classic opportunistic infection after solid organ transplantation. This review will discuss updates and future directions in the diagnosis, prevention and treatment of CMV infection in solid organ transplant recipients. Antiviral prophylaxis and pre-emptive therapy are the mainstays of CMV prevention, but they should not be mutually exclusive and each strategy should be considered depending on a specific situation. The lack of a widely applicable viral load threshold for diagnosis and preemptive therapy is emphasized as a major factor that should pave the way for an individualized approach to prevention. Valganciclovir and intravenous ganciclovir remain as drugs of choice for CMV management, and strategies for managing drug-resistant CMV infection are enumerated. There is increasing use of CMV-specific cell-mediated immune assays to stratify the risk of CMV infection after solid organ transplantation, and their potential role in optimizing CMV prevention and treatment efforts is discussed.

scholarly journals Comparison of Three Cellular Assays to Predict the Course of CMV Infection in Liver Transplant Recipients

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 88
Author(s):  
Smaranda Gliga ◽  
Melanie Fiedler ◽  
Theresa Dornieden ◽  
Anne Achterfeld ◽  
Andreas Paul ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Solid Organ Transplantation ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Cmv Infection ◽  
Cellular Assays ◽  
Risk Patients ◽  
Ifn Γ ◽  
Liver Transplant Recipients

To estimate protection from cytomegalovirus (CMV) replication after solid organ transplantation, CMV serology has been considered insufficient and thus CMV immunity is increasingly assessed by cellular in vitro methods. We compared two commercially available IFN-γ ELISpot assays (T-Track CMV and T-SPOT.CMV) and an IFN-γ ELISA (QuantiFERON-CMV). Currently, there is no study comparing these three assays. The assays were performed in 56 liver transplant recipients at the end of antiviral prophylaxis and one month thereafter. In CMV high- or intermediate-risk patients the two ELISpot assays showed significant correlation (p < 0.0001, r > 0.6) but the correlation of the ELISpot assays with QuantiFERON-CMV was weaker. Results of both ELISpot assays were similarly predictive of protection from CMV-DNAemia ≥500 copies/mL [CMV pp65 T-SPOT.CMV at the end of prophylaxis: area under curve (AUC) = 0.744, cut-off 142 spot forming units (SFU), sensitivity set to 100%, specificity 46%; CMV IE-1 T-Track CMV at month 1: AUC = 0.762, cut-off 3.5 SFU, sensitivity set to 100%, specificity 59%]. The QuantiFERON-CMV assay was inferior, reaching a specificity of 23% when setting the sensitivity to 100%. In conclusion, both CMV-specific ELISpot assays appear suitable to assess protection from CMV infection/reactivation in liver transplant recipients.

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