Improvement in Long-Term Renal Graft Survival due to CMV Prophylaxis with Oral Ganciclovir: Results of a Randomized Clinical Trial

Kliem, Volker; Fricke, Lutz; Wollbrink, T.; Burg, M. van der; Radermacher, Jörg; Rohde, Frank

doi:10.1111/j.1600-6143.2007.02133.x

Cited by 267 publications

(243 citation statements)

References 36 publications

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“…We found that eGFR was lower in both EOD and LOD patients than in patients without disease. This finding confirms the poorer prognosis associated with LOD but shows that EOD is also associated with more chronic allograft dysfunction than is seen in patients free of CMV disease, as has already been described by Kliem et al (32). Indeed, patients using a preemptive strategy (i.e.…”

Section: Discussionsupporting

confidence: 77%

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Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

Kaminski

Couzi

Garrigue³

et al. 2016

American Journal of Transplantation

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Universal prophylaxis for cytomegalovirus (CMV) prevention is viable but, compared with a preemptive strategy, leads to higher incidence of late-onset disease (LOD) associated with poor patient and graft survival. The purpose of this study was to compare LOD with early onset disease (EOD), with a focus on the highest risk kidney transplant recipients (KTRs): CMV seronegative recipients transplanted from seropositive donors (D+RÀ). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vd2-negative (Vd2 neg ) cd T cell expansion involved in CMV infection resolution. EOD was defined as occurring <3 mo and LOD as occurring >3 mo after transplantation. Depending on the period, universal prophylaxis or preemptive treatment was used. Overall, 168 D+RÀ KTRs were included between 2003 and 2011. LOD was associated with a lower peak DNAemia (p = 0.04), fewer recurrences (odds ratio 0.16; 95% confidence interval 0.05-0.55; p = 0.01) and shorter anti-CMV curative treatment (40 vs. 60 days, p < 0.0001). As a corollary, we found that Vd2 neg cd T cell expansion was faster in LOD than in EOD (31 vs. 168 days after the beginning of CMV disease, p < 0.0001). In D+RÀ KTRs, universal prophylaxis is associated with more LOD, which had better infection management and a faster immune response. These results support the use of universal prophylaxis over a preemptive strategy and reappraise outcomes of LOD.

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Section: Discussionsupporting

confidence: 77%

“…Indeed, patients using a preemptive strategy (i.e. a marker of early disease) had lower graft survival than patients who received universal prophylaxis (32), but direct comparison between EOD and LOD was not done.…”

Section: Discussionmentioning

confidence: 99%

Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

Kaminski

Couzi

Garrigue³

et al. 2016

American Journal of Transplantation

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“…Furthermore, most studies have indicated that successful antiviral prophylaxis has a beneficial effect on long-term graft function (8). This suggests that viral replication is a component of risk, but the precise mechanisms underlying this effect are debated (9,11,(26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

The Cell Biology of Cytomegalovirus: Implications for Transplantation

Kaminski

Fishman

2016

American Journal of Transplantation

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Interpretation of clinical data regarding the impact of cytomegalovirus (CMV) infection on allograft function is complicated by the diversity of viral strains and substantial variability of cellular receptors and viral gene expression in different tissues. Variation also exists in nonspecific (monocytes and dendritic cells) and specific (NK cells, antibodies) responses that augment T cell antiviral activities. Innate immune signaling pathways and expanded pools of memory NK cells and cd T cells also serve to amplify host responses to infection. The clinical impact of specific memory T cell anti-CMV responses that cross-react with graft antigens and alloantigens is uncertain but appears to contribute to graft injury and to the abrogation of allograft tolerance. These responses are modified by diverse immunosuppressive regimens and by underlying host immune deficits. The impact of CMV infection on the transplant recipient reflects cellular changes and corresponding host responses, the convergence of which has been termed the "indirect effects" of CMV infection. Future studies will clarify interactions between CMV infection and allograft injury and will guide interventions that may enhance clinical outcomes in transplantation.

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“…Important considerations are the indirect effects of CMV on transplant-related endpoints, such as rejection and long-term graft function, which are linked to CMV by circumstantial evidence. Some studies show an advantage of prophylaxis over preemption for these indirect effects [7], while others do not [8,9]. The major hurdles for the preemptive strategy are the logistics necessary not only to ensure timely assessment of biomarkers, but also to take appropriate and prompt action upon receipt of the result.…”

Section: Discussionmentioning

confidence: 99%

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

et al. 2012

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Background The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. Methods We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n = 84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n = 74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate-and high-risk group. Follow-up was truncated at 6 months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation.Results Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26 %) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p = 0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. Conclusions The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successful.

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Improvement in Long-Term Renal Graft Survival due to CMV Prophylaxis with Oral Ganciclovir: Results of a Randomized Clinical Trial

Cited by 267 publications

References 36 publications

Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

Easier Control of Late-Onset Cytomegalovirus Disease Following Universal Prophylaxis Through an Early Antiviral Immune Response in Donor-Positive, Recipient-Negative Kidney Transplants

The Cell Biology of Cytomegalovirus: Implications for Transplantation

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation

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