CSI Clinical Science Investigations: Where Science Meets the Bedside

12:50 Cytomegalovirus disease in solid organ transplantation
J. Andrew Bradley, University of Cambridge, Cambridge, UK

Cytomegalovirus (CMV) remains the most common viral pathogen that results in clinically important infection in recipients of solid organ transplants. Primary infection causes the most severe disease and CMV seronegative recipients of grafts from CMV seropositive donors are at greatest risk. CMV infection in seropositive recipients is also common, as a result of reactivation of latent CMV infection or occasionally re-infection with a different strain of CMV, and may also result in significant morbidity and even mortality. There is currently much debate about the relative merits of routine anti-viral prophylaxis versus monitoring for viral load and pre-emptive anti-viral therapy. Although established CMV infection usually responds well to first-line anti-viral therapy, relapse is common and use of second-line therapy may sometimes be required for resistant disease.

Illustrative Case: A 56-year-old Caucasian with chronic renal failure of unknown cause (presumed glomerulonephritis), in otherwise good health, received a living donor kidney transplant from his haploidentical sister. Anti-CD25 induction therapy and calcineurin-based immunosuppression plus steroids and azathioprine were used. Both recipient and donor were CMV seropositive and no anti-viral prophylaxis was given. The patient made a good initial recovery but within several weeks developed CMV infection which responded well to intravenous ganciclovir. However, over the course of the next several months he required a number of hospital admissions for recurrent CMV infection and eventually developed ganciclovir-resistant CMV that required treatment with foscarnet.
Because of continuing complex CMV-related problems, it became necessary to significantly reduce and eventually stop immunosuppressive therapy. His renal graft failed as a result and transplant nephrectomy was performed 9 months after transplantation. Even in the absence of any exogenous immunosuppression and despite continued treatment with second-line therapy for CMV infection, CMV viraemia persisted and his condition progressively deteriorated with the development of lymphopenia and CNS symptoms. The patient eventually became comatose and died after a further 4 months (13 months after transplantation).

Although this is an exceptional and extreme example of CMV disease following renal transplantation, it has a number of important learning points and highlights the complexity and potential seriousness of CMV infection. There is a clear need for further research into how best to prevent, diagnose and manage CMV disease in transplant patients and current developments in these areas will be briefly reviewed.