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

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+R-). Since CMV control depends on both antiviral treatment and specific immune response, we also compared Vδ2-negative (Vδ2(neg) ) γδ 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+R- 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 Vδ2(neg) γδ 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+R- 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.

Two-year post-transplantation cytomegalovirus DNAemia in asymptomatic kidney transplant recipients: incidence, risk factors, and outcome.

BACKGROUND: The incidence and the impact of asymptomatic cytomegalovirus (CMV) DNAemia occurring after the first year post transplantation is unknown. METHODS: In this retrospective cross-sectional study, we analyzed the incidence, risk factors, and impact of 2-year post-transplantation asymptomatic CMV DNAemia (2YCD) on graft function. We included 892 consecutive asymptomatic kidney transplant recipients transplanted for at least 2 years and all were monitored using whole blood CMV quantitative nucleic acid amplification testing (CMV-QNAT). RESULTS: Twenty-eight patients displayed 2YCD (3.1%). Using multivariate analysis in 578 patients, we found that female gender (odds ratio [OR] = 2.57, P = 0.02), a past history of CMV drug-resistance mutation (OR = 8.73, P = 0.005), and corticosteroid use (OR = 2.37, P = 0.03) were independently associated with an increased risk of 2YCD. 2YCD was associated with an increased incidence of subsequent CMV disease over the year following its diagnosis (7% vs. 0.6%, P = 0.02). Patients with 2YCD also exhibited a declining estimated glomerular filtration rate more frequently (77%) than patients with a negative CMV-QNAT (56%, P = 0.02). CONCLUSION: 2YCD appears to be a rare entity, which appears to be associated with chronic graft dysfunction.

[Immune dysfuntion of uremic patients: potential role for the soluble form of CD40]. / Troubles immunitaires de l'insuffisance rénale chronique: vers une implication de la forme soluble du CD40.

Immune deficiency is one of the numerous physiological alterations associated with chronic renal failure. Recurrent bacterial infections, diminished vaccinal response or beta2-microglobuline amyloïdosis are some common features of clinically well known dysregulations of uraemic immune functions. During the last ten years, our knowledge concerning the molecular and cellular effectors involved in the immune response has considerably progressed. Recent data clearly demonstrated that despite their activated phenotype, the effector capacity of the immune cells are severely hampered. Of interest, those abnormalities are not corrected by haemodialysis which sometimes even accentuate them. However, the presence of uraemic toxins in the serum of chronic renal failure patients jeopardise the determination of the factors responsible for the alteration of immune response in those patients. Among those molecules, the soluble form of CD40 (sCD40), which seric levels are dramatically increased, seems to play a crucial role. A better understanding of the molecular and cellular actors involved in the immune disorders of uraemic patients should allows the emergence of new immuno-intervention strategies and improve haemodialysis traitement.

Cytomegalovirus infection in transplant recipients resolves when circulating gammadelta T lymphocytes expand, suggesting a protective antiviral role.

gammadelta T cells undergo massive expansion in the peripheral blood of renal transplant recipients who are infected with cytomegalovirus (CMV). In a 3-year prospective study, the relationship between the evolution of CMV infection and the kinetics of gammadelta T cell amplification was followed for 10 months after transplantation. Patients with late gammadelta T cell expansion (>/=45 days) had significantly longer (P<.0001) and higher (P<.0003) pp65 antigenemia and more-symptomatic CMV disease than did patients with early expansion. Analysis of data for each patient showed that gammadelta T cell expansion is concomitant with the resolution of CMV infection and disease, regardless of the CMV serologic status of donor and recipient before transplantation. These observations point to gammadelta T cell percentage determination as a new, rapid, and reliable prognosis factor to predict the resolution of CMV infection and strongly suggest that gammadelta T cells play a protective role against CMV infection.