valganciclovir and Renal-Insufficiency

We report two CMV naïve children who received deceased donor renal transplants from a CMV IgG-negative single donor. CMV IgG in both recipients and the donor were negative immediately prior to transplant. Both recipients had early recurrences of their original disease in their transplants, requiring multiple sessions of plasmapheresis. All blood products used were leukoreduced or CMV seronegative. A few days post-transplant, both recipients developed significant positive CMV viremia. Both required initiation of oral valganciclovir. Case 1 responded to oral valganciclovir only while the case 2 had a delayed response to it and hence required intravenous ganciclovir with good response. When checked retrospectively, CMV IgM in the donor was positive along with positive CMV DNA PCR from the white cells. Here we describe a very unusual scenario of CMV transmission in two pediatric renal transplant recipients from a single donor during the CMV window period.

Topics: Administration, Oral; Adolescent; Antibodies, Viral; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Humans; Immunoglobulin G; Immunoglobulin M; Kidney Transplantation; Male; Postoperative Period; Renal Insufficiency; Retrospective Studies; Risk Factors; Transplant Recipients; Treatment Outcome; Valganciclovir

There is notable heterogeneity in the implementation of cytomegalovirus (CMV) prevention practices among CMV-seropositive (R+) kidney transplant (KT) recipients. In this prospective observational study, we included 387 CMV R+ KT recipients from 25 Spanish centers. Prevention strategies (antiviral prophylaxis or preemptive therapy) were applied according to institutional protocols at each site. The impact on the 12-month incidence of CMV disease was assessed by Cox regression. Asymptomatic CMV infection, acute rejection, graft function, non-CMV infection, graft loss, and all-cause mortality were also analyzed (secondary outcomes). Models were adjusted for a propensity score (PS) analysis for receiving antiviral prophylaxis. Overall, 190 patients (49.1%) received preemptive therapy, 185 (47.8%) antiviral prophylaxis, and 12 (3.1%) no specific intervention. Twelve-month cumulative incidences of CMV disease and asymptomatic infection were 3.6% and 39.3%, respectively. Patients on prophylaxis had lower incidence of CMV disease [PS-adjusted HR (aHR): 0.10; 95% confidence interval (CI): 0.01-0.79] and asymptomatic infection (aHR: 0.46; 95% CI: 0.29-0.72) than those managed preemptively, with no significant differences according to the duration of prophylaxis. All cases of CMV disease in the prophylaxis group occurred after prophylaxis discontinuation. There were no differences in any of the secondary outcomes. In conclusion, antiviral prophylaxis was associated with a lower occurrence of CMV disease in CMV R+ KT recipients, although such benefit should be balanced with the risk of late-onset disease.

Topics: Adult; Aged; Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Incidence; Kaplan-Meier Estimate; Kidney Transplantation; Male; Middle Aged; Propensity Score; Proportional Hazards Models; Prospective Studies; Renal Insufficiency; Risk Factors; Spain; Valganciclovir

Topics: Antibodies, Monoclonal; Basiliximab; Cytomegalovirus; Cytomegalovirus Infections; Female; Ganciclovir; Glomerulonephritis, IGA; HIV Seronegativity; Humans; Immunosuppression Therapy; Inflammation; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Prednisolone; Recombinant Fusion Proteins; Renal Dialysis; Renal Insufficiency; Sinusitis; Tacrolimus; Valganciclovir

Many children receiving a kidney transplant are seronegative for CMV and therefore, highly susceptible to a primary CMV infection. This study aims at evaluating incidence, time of occurrence, and severity of CMV infection in the first year post-transplantation in relation to different types of CMV prophylaxis. Transplantations in three centers in the Netherlands between 1999 and 2010 were included. Retrospective, observational, multicenter study. Clinical data and PCR measurements of CMV were collected. Prophylaxis in high-risk patients (CMV serostatus D+R-) consisted of (val)ganciclovir during three months, or acyclovir plus CMV immunoglobulin at a former stage. Intermediate-risk patients (R+) received (val)acyclovir, or acyclovir plus CMV immunoglobulin at a former stage. Low-risk patients (D-R-) did not receive prophylaxis. Infection was defined as CMV PCR above 50 geq/mL plasma or whole blood, a clinically relevant infection above 1000 geq/mL. One hundred and fifty-nine transplantations were included. CMV infection was documented for 41% of high-risk, 24% of intermediate-risk, and 13% of low-risk patients, in the latter two groups typically during the first three months. The infection rate was highest in the high-risk group after cessation of valganciclovir prophylaxis. Valganciclovir provided better protection than did acyclovir + CMV immunoglobulin. Adding an IL2-receptor blocker to the immunosuppressive regimen did not affect the infection rate. Acute graft rejection was not related with CMV infection. Valganciclovir prophylaxis effectively prevents CMV infection in high-risk pediatric kidney recipients, but only during prophylaxis. Valacyclovir prophylaxis in intermediate-risk patients is less effective.

Topics: Acyclovir; Adolescent; Antiviral Agents; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections; Disease-Free Survival; Ganciclovir; Humans; Immunoglobulins; Immunosuppressive Agents; Infant; Kidney Transplantation; Netherlands; Polymerase Chain Reaction; Receptors, Interleukin-2; Renal Insufficiency; Retrospective Studies; Risk; Valacyclovir; Valganciclovir; Valine