Evaluation of practices for the diagnosis and monitoring of cytomegalovirus infection in kidney transplant recipients in Brazil

Cytomegalovirus (CMV) remains a significant challenge in kidney transplantation. Despite prophylactic and preemptive antiviral strategies, clinical practices vary widely. This study assessed CMV diagnostic and monitoring practices in Brazilian kidney transplant centers, focusing on access to diagnostic tools, therapeutic thresholds, and logistical barriers. A nationwide electronic survey was conducted between August and October 2024, targeting all kidney transplant programs (TP) registered with the Brazilian Society of Organ Transplantation (ABTO). A total of 35 TP (20.6% response rate) participated, representing 62% of kidney transplants performed in Brazil in 2023. While most centers had CMV management protocols (94.3%), significant variability was observed in the initiation of preemptive therapy (PET). Among high-risk patients (D+/R-), 41.9% followed predefined thresholds. Specific cut-off values were applied in 71.0% of R+ patients and in 45.2% of the low-risk group (D-/R-). Quantitative PCR was the primary diagnostic method (97.1%), with whole blood (60%) and plasma (34.3%) as preferred sample types. A significant proportion of CMV TP (60%) relied on outsourced laboratories for CMV diagnostics, with 82.4% experiencing turnaround times exceeding three days for results. Only 8.6% TP had access to molecular testing for CMV-resistant strains. This survey reveals substantial variability in CMV diagnosis and management among Brazilian kidney transplant centers, with limited diagnostic access and delays due to reliance on outsourced laboratories. Expanding diagnostic capacity and standardizing guidelines are essential to improving patient outcomes.

Cytomegalovirus prevention strategies and the risk of BK polyomavirus viremia and nephropathy.

BackgroundVaricella zoster virus (VZV) infection is a well-known opportunistic infection in solid organ transplant recipients. Since the various strategies of the use of anti-herpetic drugs including ganciclovir or acyclovir have evolved, the epidemiology of VZV infection is changing. However, there are limited data on the recent incidence and risk factors of post-transplant VZV infection in popular preemptive ganciclovir era for CMV infection. We evaluated the incidence, risk factors and clinical characteristic of patients with development of post-transplant VZV infection in kidney transplant (KT) recipients after 1-month acyclovir prophylaxis in the hospital that adopted preemptive ganciclovir therapy for CMV infection.MethodsAll adult patients with seropositive CMV antibody admitted to a KT unit from January 2014 to December 2017 were retrospectively reviewed in a tertiary-care hospital in South Korea. Our hospital adopted preemptive ganciclovir therapy for CMV infection in all CMV seropositive KT recipients. We administered acyclovir prophylaxis for 1-month to CMV seropositive KT recipients. The primary endpoint was VZV infection development after KT.ResultsA total of 1295 KT recipients was followed up for 4295.8 person-years. The median follow-up period was 46.6 months (interquartile range (IQR) 34.3-59.5). Of the 1295 recipients, 100 (7.7%, 2.33 per 100 person-years, 95% confidence interval (CI) 1.89-2.83) patients developed VZV infection after KT. The median time for VZV infection development was 9.5 months (IQR 4.7-22.1). All patients had VZV-associated skin lesion, 9 postherpetic neuralgia, 2 visceral involvement and 3 disseminated infection. Of 100 patients, 16 patients need hospitalization due to VZV infection. In multivariate analysis, deceased donor KT (Hazard ratio (HR) 1.6; 95% CI 1.0-2.39, p = 0.05), mycophenolate maintenance immunosuppressive therapy (HR 0.3; 95% CI 0.14-0.75, p = 0.01) and rejection episode (HR 0.31; 95% CI 0.14-0.71, p = 0.01) were independently associated with VZV infection development after KT.ConclusionAbout one tenth of CMV seropositive KT recipients developed zoster after 1-month ACV prophylaxis during CMV preemptive strategy, especially in those who received deceased donor KT, mycophenolate therapy, and rejection episodes.DisclosuresAll Authors: No reported disclosures

Does the cytomegalovirus infection cause kidney transplant rejection in Erbil city patients, Kurdistan region of Iraq?

The Best Method for CMV Prevention in High-risk Kidney Transplant Recipients? Either, per National Norwegian Transplant Database: Commentary on Blom et al, Cytomegalovirus High-risk Kidney Transplant Recipients Show No Difference in Long-term Outcomes Following Preemptive Versus Prophylactic Management.

Introduction The specific mechanism that can explain the linking of Citomegalovirus (CMV) infection with diminished graft function is not totally clear due to there are numerous issues involved. Some cytokines with antiviral proprieties such as interferon gamma (IFN-γ) have been studied. In fact, the SNP +874 A/T of IFN-γ gene, which is linked to their levels, has been associated with increased risk of CMV infection in both lung and kidney transplant recipients. Our purpose was to replicate the association of this SNPin an independent population of kidney transplant patients. Materials and Methods A retrospective analysis was performed in 600 consecutive transplanted kidney recipients. The SNP+874 A/T (rs2430561) was genotyped by TaqMan chemistry under conditions recommended by manufacturer and analyzed in a 7900HT Fast Real-Time PCR System (Applied Biosystem, Foster City, CA, USA). CMV viral load was determined by quantitative nucleic acid amplification testing (QNAT). Results and Discussion Patients with CMV infection were 205 (34.2%) and the median time after transplant to the onset of CMV infection was 2.7 months (range 1.2-5.3 months).We found no association of IFN-γ+874 A/T polymorphism in either univariate or multivariate analyses and regardless of prophylactic treatment with valganciclovir (Tables 1 and 2). Due to antiviral properties of this cytokine and the implication of the aforementioned polymorphism in their level, it would seem the most appropriate approach to assess the risk of CMV infection; however, this association could not be stablished in our well powered cohort. The previously reported association of IFN-γ +874 A/T polymorphism with CMV infection in kidney transplant and lung transplant recipients showed 52 and 42 CMV positives patients respectively. In the adjusted model we found interactions between prophylaxis with status CMV D+ / R- (P-interaction = 0.010), with thymoglobulin induction therapy (P-interaction = 0.034) and with thymoglobulin anti-rejection therapy (P-interaction = 0.002). Data showed that CMV seropositive recipients and no thymoglobulin therapy, the prophylaxis with valganciclovir is not an advantage (Table 2); however if thymoglobulin is used for induction and/or rejection, valganciclovir profilaxis is a protective key for CMV infection (Table 2). Related to well-known associated factors, increased infection risk was observed for recipient age, delayed graft function and (initial immunosuppressive treatment with mammalian target of rapamycin inhibitors (mTORi), (Table 2).Conclusion Our data suggest that IFN-γ +874 A/T polymorphism is not a predictive marker of CMV infection in a Spanish cohort of kidney transplant patients, the thymoglobulin therapy is not a risk factor for CMV infection when it is associated with prophylaxis with valganciclovir and the protective effect of imTORis not improved with prophylactic treatment.

Clinical practice guidelines for the provision of renal service in Hong Kong: Potential Kidney Transplant Recipient Wait-listing and Evaluation, Deceased Kidney Donor Evaluation, and Kidney Transplant Postoperative Care.

Monitoring of CMV-specific cell-mediated immunity with a commercial ELISA-based interferon-γ release assay in kidney transplant recipients treated with antithymocyte globulin.

Peripheral Blood Absolute Lymphocyte Count as a Predictor of Cytomegalovirus Infection in Kidney Transplant Recipients

COVID-19 in Kidney Transplantation: Outcomes, Immunosuppression Management, and Operational Challenges.

Human Cytomegalovirus and Kidney Transplantation: A Clinician's Update

Clinical Usefulness of Plasma Quantitative Polymerase Chain Reaction Assay: Diagnosis of Cytomegalovirus Infection in Kidney Transplant Recipients

Background/Aims:Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy.Methods:We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period.Results:The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001).Conclusions:The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.

Cytomegalovirus (CMV) and BK polyomavirus (BKPyV) infections after kidney transplant have become increasingly prevalent. Based on previous studies, the mammalian target of rapamycin (mTOR) inhibitors seem like attractive alternatives with antiviral activity. The objective of this systematic review and meta-analysis was to investigate the incidence of CMV and BKPyV infections in kidney transplantation recipients receiving mTOR inhibitors. This meta-analysis included three comparisons of immunosuppressant regimens commonly used after kidney transplantation: Comparison 1: mTOR inhibitors versus calcineurin inhibitors (CNI); Comparison 2: mTOR inhibitors versus antimetabolites (AM); and Comparison 3: mTOR inhibitors plus a reduced-dose of CNI versus AM plus a standard-dose of CNI. The group containing mTOR inhibitors was the study group and the remaining one was the control group. The incidence of CMV or BKPyV infection defined by positive culture, serology, or polymerase chain reaction testing was the primary outcome. A total of 61 studies involving 13,609 patients were included. As compared with the control group, a significantly decreased risk of CMV and BKPyV infections favoring the mTOR inhibitors-based group was shown in comparisons 1, 2, and 3 (p < 0.05). Compared with the control group in all three comparisons, mTOR inhibitors made no difference in regard to death and graft loss (p > 0.05). Compared with CNI, the incidence of biopsy-proven acute rejection (BPAR) and anemia was higher with mTOR inhibitors (p < 0.05). In comparisons 2 and 3, the risk of new-onset diabetes mellitus (NODM) was higher with mTOR inhibitors (p < 0.05). Early introduction of mTOR inhibitors reduced more CMV infections in comparisons 1 and 2 (p < 0.05). The mTOR inhibitor-based regimen is an attractive alternative with lower risk of CMV and BKPyV infections in kidney transplant recipients. The combination regimen is more appropriate and acceptable than the mTOR-inhibitor monotherapy-based regimen. Early introduction of mTOR inhibitors is recommended, although it is worth noting that attention should be paid to wound healing when mTOR inhibitors are introduced early.

Background and Aims Kidney transplant recipients are vulnerable to viral infections due to immunosuppressive therapy. Whilst there is recognition on the increased risk of Monkeypox (Mpox) infection in kidney transplant recipients, there remain limited discussion detailing disease progression, the effectiveness of current management strategies, and how immunosuppression influences disease course in kidney transplant recipients diagnosed with Mpox infection. As Mpox infection could potentially be severe and fatal, with case incidence continuing to rise globally, there is a need to develop tailored guidance to manage kidney transplant recipients with Mpox infection. To this end, we conducted a systematic review of current publications which described Mpox infection in kidney transplant recipients. Method This study is registered with PROSPERO (CRD42024611601). A systematic literature search was performed for full-text articles published in English between Aug 2014 and Aug 2024 through the PRISMA guideline. The inclusion criteria encompassed publications which examined the prevalence, incidence and/or impact of Mpox infection in kidney transplant recipients, and publications reporting on clinical outcomes such as graft failure, mortality or adverse events in kidney transplant recipients with Mpox infection. Publications which did not report data on Mpox infection in kidney transplant recipients and inaccessible full-text publications were excluded. Literature search was conducted by three independent authors (H.H.L.W., O.S. and M.J.). Databases used included PubMed, EMBASE, MEDLINE, Cochrane Library and Scopus. Combination keywords used included: “Monkeypox” AND “Kidney Transplant” AND “Immunosuppression”; “Mpox” AND “Kidney transplant” AND “Immunosuppression”; “Monkeypox” AND “Renal Transplant” AND “Immunosuppression”; “Mpox” AND “Renal Transplant” AND “Immunosuppression”; “Monkeypox” AND “Kidney Transplant”; “Mpox” AND “Kidney Transplant”; “Monkeypox” AND “Renal Transplant”; “Mpox” AND “Renal Transplant”; “Monkeypox” AND “Immunosuppression”; “Mpox” AND “Immunosuppression”; “Monkeypox” AND “Kidney Transplant” AND “Infection Management”; “Mpox” AND “Kidney Transplant” AND “Infection Management”; “Monkeypox” AND “Renal Transplant” AND “Infection Management”; “Mpox” AND “Renal Transplant” AND “Infection Management”. Publications identified in the databases were imported into Mendeley, where duplicates were removed. H.H.L.W., O.S. and M.J. then independently reviewed the remaining publications. Results A total of 12,429 articles were initially screened through our search strategy. After evaluation for relevance and applying our defined inclusion and exclusion criteria, 16 publications were included in the final review (Fig. 1). Table 1 provides a summary of included publications. Severity of Mpox can manifest in disseminated forms, including multi-organ involvement such as skin, lung, and pleural complications. Acute kidney injury and aggravation of kidney function was not uncommonly observed. Clinical outcomes were poor and fatalities were high in kidney transplant recipients with other immunocompromised conditions such as HIV. Prompt diagnosis of Mpox infection in kidney transplant recipients to facilitate timely initiation of antiviral treatment may be critical to improving outcomes. In particular, Tecovirimat was reported as an effective treatment option to mitigate the severity of Mpox infection in kidney transplant recipients and aid patient recovery. Modifying or temporarily discontinuing immunosuppression with close monitoring for signs of graft rejection is also considered a key measure to improving outcomes. Conclusion This systematic review underscores the heightened risk of severe Mpox infections in kidney transplant recipients due to their immunocompromised status. Current publications revealed a range of clinical presentations from disseminated infections to severe systemic involvement, emphasizing the need for vigilant monitoring and timely intervention with antiviral therapies if indicated.