Abstract

Previous reports hypothesized that cytomegalovirus (CMV) may predispose to non-CMV infection after kidney transplantation (KT). We analysed the incidence of non-CMV infection (overall, bacterial and opportunistic) in 291 KT recipients according to the previous development of any level or high-level (≥1,000 IU/ml) CMV viremia. Exposure to CMV replication was assessed throughout fixed intervals covering first the 30, 90, 180 and 360 post-transplant days (cumulative exposure) and non-overlapping preceding periods (recent exposure). Adjusted Cox models were constructed for each landmark analysis. Overall, 67.7 and 50.5% patients experienced non-CMV and CMV infection, respectively. Patients with cumulative CMV exposure had higher incidence of non-CMV infection beyond days 30 (p-value = 0.002) and 90 (p-value = 0.068), although these associations did not remain after multivariable adjustment. No significant associations were observed for the remaining landmark models (including those based on high-level viremia or recent CMV exposure), or when bacterial and opportunistic infection were separately analysed. There were no differences in viral kinetics (peak CMV viremia and area under curve of CMV viral load) either. Our findings do not support the existence of an independent association between previous CMV exposure and the overall risk of post-transplant infection, although results might be affected by power limitations.

Highlights

  • Despite notable advances in diagnosis, prevention and treatment, cytomegalovirus (CMV) remains as a leading cause of morbidity after solid organ transplantation (SOT) due to its direct pathogenic effects

  • Previous studies have suggested that CMV replication increases the risk of bacterial infection (Listeria monocytogenes [23, 24] or Clostridioides difficile [21, 25, 26]), nonCMV viral infection (hepatitis C virus [27]) and, opportunistic events such as invasive aspergillosis, [28,29,30] nocardiosis [31] or Pneumocystis jirovecii pneumonia. [22, 32, 33] It should be noted that this evidence is mainly based on retrospective case-control studies with small sample sizes

  • Several reports have suggested that CMV would increase the risk of certain non-CMV infections in SOT and allo-HSCT recipients, [12, 22, 23, 25, 27, 29, 32, 33, 40, 41] which provided the clinical foundation for hypothesizing about its presumptive immunomodulatory effects

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Summary

Introduction

Despite notable advances in diagnosis, prevention and treatment, cytomegalovirus (CMV) remains as a leading cause of morbidity after solid organ transplantation (SOT) due to its direct pathogenic effects. [17, 18] These immunomodulatory effects, maintained over time, are thought to underlie the deleterious consequences allegedly caused by CMV It is controversial, whether reducing CMV replication with the use of antiviral prophylaxis would impact the incidence of post-transplant events [19,20,21,22]. Misclassification bias in case-control studies cannot be excluded, as recipients that had previously experienced infectious complications might have been more closely monitored for CMV replication during the subsequent follow-up. It remains unclear whether the demonstration of CMV infection merely acts as a surrogate marker for over-immunosuppression

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