Risk factors for late‐onset cytomegalovirus disease in donor seropositive/recipient seronegative kidney transplant recipients who receive antiviral prophylaxis

Abstract

Background Cytomegalovirus (CMV) disease occurs frequently after cessation of antiviral prophylaxis in CMV-seronegative kidney transplant recipients from seropositive donors (D+ R−), and the risk factors are incompletely defined. Methods We retrospectively assessed the incidence, clinical features, and risk factors for CMV disease in a cohort of D+ R− kidney transplant recipients who received antiviral prophylaxis at a single US transplant center using descriptive statistics and Cox proportional hazards models. Results CMV disease developed in 29 of 113 (26%) D+ R− patients at a median of 185 days (interquartile range 116–231 days) post transplant, including CMV syndrome (66%) and tissue invasive disease (34%). The incidence of CMV disease was higher in patients who underwent re-transplantation (57% vs. 24%) and this factor was independently associated with a higher risk of CMV disease in multivariable analysis (hazard ratio, 4.02; 95% confidence interval, 1.3–13; P = 0.016). Other demographic and transplant variables were not independently associated with a risk of late-onset CMV disease. Conclusions Despite a comprehensive analysis of patient and transplant variables, only re-transplantation was identified as a risk factor for CMV disease in D+ R− kidney transplant recipients who received antiviral prophylaxis, but had limited clinical predictive value. The development of novel laboratory markers to identify patients at greatest risk for CMV disease should be a priority for future studies.

CMV: Prevention, Diagnosis and Therapy

“…In another series of D+/R− kidney recipients, 51 patients (29%) developed CMV disease at a median of 61 days (interquartile range, 40-143 days) after stopping 3 months of antiviral prophylaxis (19). In a third series of D+/R− renal transplant recipients on 3 to 6 months of antiviral prophylaxis, CMV disease developed in 29 of 113 (26%) at a median of 185 days posttransplant (range 116-231 days), including CMV syndrome (66%) and tissue invasive disease (34%) (20). All series have a relatively high rate of late CMV, underscoring the ability of preventative antiviral therapy to delay but not prevent CMV infection.…”

“…A metaanalysis of 11 randomized trials (698 patients; median follow-up: 12 months, range: 3-22 months), with six randomized trials (302 patients) after kidney transplantation, demonstrated a beneficial effect of the prophylactic use of CMV immunoglobulin on total survival and prevention of Should not be used 1500 mg once a day, or 500 mg three times a day Should not be used 1000 mg once a day, or 500 mg twice a day [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Should not be used 500 mg once a day <10…”

Impaired Direct Priming of CD8 T Cells by Donor-Derived Cytomegalovirus Following Kidney Transplantation

“…However, sensitive DNA-based techniques commonly detect CMV persistence after transplantation in kidneys from seropositive donors, 24 suggesting that donor tissue may act as a "reservoir" for infection, which may later become clinically manifest. 25 Certainly the preimplantation histologic data from the current study suggest peri-transplantation CMV transmission is very common. After CMV reactivation, HLA class I upregulation occurs in infected and surrounding cells, [26][27][28][29] with subsequent presentation of CMVantigens to CD8+ T cells.…”

Update on Cytomegalovirus Infections of the Gastrointestinal System in Solid Organ Transplant Recipients

“…One major disadvantage of the universal prophylaxis strategy is the development of late-onset CMV disease, disease which occurs after the discontinuation of prophylaxis. Late-onset CMV disease occurs in up to 30% of high risk D+/Rrecipients, and is associated with allograft loss and mortality [60][61][62]. This presumably occurs due the lack of development of CMV-specific cell-mediated immunity in this population.…”

“…This presumably occurs due the lack of development of CMV-specific cell-mediated immunity in this population. Risk factors for late-onset CMV disease include D+/R-serostatus, higher immunosuppression, retransplantation, and graft rejection [61,63]. Prevention of late-onset CMV disease remains an area where further study is needed, follow-up data from the IMPACT study suggest that extended duration valganciclovir prophylaxis is associated with long-term reduction in CMV disease at 2 years post-transplant [64•].…”