Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.

https://www.zora.uzh.ch/id/eprint/165728/1/document%281%29.pdf

The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation

Cytomegalovirus (CMV) infection and disease are important causes of morbidity and mortality among transplant recipients. For the purpose of developing consistent reporting of CMV in clinical trials, definitions of CMV infection and disease were developed and published. This study seeks to update the definitions of CMV on the basis of recent developments in diagnostic techniques, as well as to add to these definitions the concept of indirect effects caused by CMV.

Definitions of Cytomegalovirus Infection and Disease in Transplant Recipients

A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study).

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1600-6143.2004.00382.x

Efficacy and safety of valganciclovir vs. oral ganciclovir for prevention of cytomegalovirus disease in solid organ transplant recipients.

BackgroundIn previous analyses of BENEFIT, a phase 3 study, belatacept-based immunosuppression, as compared with cyclosporine-based immunosuppression, was associated with similar patient and graft survival and significantly improved renal function in kidney-transplant recipients. Here we present the final results from this study. MethodsWe randomly assigned kidney-transplant recipients to a more-intensive belatacept regimen, a less-intensive belatacept regimen, or a cyclosporine regimen. Efficacy and safety outcomes for all patients who underwent randomization and transplantation were analyzed at year 7 (month 84). ResultsA total of 666 participants were randomly assigned to a study group and underwent transplantation. Of the 660 patients who were treated, 153 of the 219 patients treated with the more-intensive belatacept regimen, 163 of the 226 treated with the less-intensive belatacept regimen, and 131 of the 215 treated with the cyclosporine regimen were followed for the full 84-month period; all avail...

/pdf/belatacept-and-long-term-outcomes-in-kidney-transplantation-xznnb5bjby.pdf

Belatacept and Long-Term Outcomes in Kidney Transplantation.

Background Cytomegalovirus (CMV) disease is a major complication of organ transplantation. We hypothesized that prophylactic treatment with valacyclovir would reduce the risk of CMV disease. Methods A total of 208 CMV-negative recipients of a kidney from a seropositive donor and 408 CMV-positive recipients were randomly assigned to receive either 2 g of valacyclovir or placebo orally four times daily for 90 days after transplantation, with the dose adjusted according to renal function. The primary end point was laboratory-confirmed CMV disease in the first six months after transplantation. Results Treatment with valacyclovir reduced the incidence or delayed the onset of CMV disease in both the seronegative patients (P<0.001) and the seropositive patients (P=0.03). Among the seronegative patients, the incidence of CMV disease 90 days after transplantation was 45 percent among placebo recipients and 3 percent among valacyclovir recipients. Among the seropositive patients, the respective values were 6 percent and 0 percent. At six months, the incidence of CMV disease was 45 percent among seronegative recipients of placebo and 16 percent among seronegative recipients of valacyclovir; it was 6 percent among seropositive placebo recipients and 1 percent among seropositive valacyclovir recipients. At six months, the rate of biopsy-confirmed acute graft rejection in the seronegative group was 52 percent among placebo recipients and 26 percent among valacyclovir recipients (P=0.001). Treatment with valacyclovir also decreased the rates of CMV viremia and viruria, herpes simplex virus disease, and the use of inpatient medical resources. Hallucinations and confusion were more common with valacyclovir treatment, but these events were not severe or treatment limiting. The rates of other adverse events were similar among the groups. Conclusions Prophylactic treatment with valacyclovir is a safe and effective way to prevent CMV disease after renal transplantation. (N Engl J Med 1999; 340:1462-70.) (C) 1999, Massachusetts Medical Society.

https://www.nejm.org/doi/pdf/10.1056/NEJM199905133401903

Valacyclovir for the Prevention of Cytomegalovirus Disease after Renal Transplantation

BACKGROUND: Renal-transplant recipients have shortened life expectancy primarily because of premature cardiovascular disease. Traditional and nontraditional risk factors for cardiovascular disease ...

Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation: experience from the Assessment of Lescol in Renal Transplantation trial.

Background. No prospective study has been performed to determine the prognostic value of 24-hr ambulatory blood pressure (24-hr ABP) versus casual blood pressure (CBP) in patients after kidney transplantation. We have addressed this issue by analyzing renal graft function in patients for the first 5 years after transplantation. Methods. The 24-hr ABP (SpaceLabs 90207) was monitored 6 and 18 months after transplantation in 46 renal transplant recipients without any acute episodes of rejection. Combined study endpoints were death of patients, need for dialysis, second transplantation, and doubling of serum creatinine. Results. Six months after transplantation systolic and diastolic 24-hr ABP correlated with serum creatinine (r=0.41, P=0.005 and r=0.37, P<0.01, respectively) although CBP did not. Divided into tertiles according to average 24-hr ABP (lower tertile: ≤91 mmHg; middle tertile: 92-97 mmHg; upper tertile: ≥98 mmHg) serum creatinine significantly differed between the three groups (1.26±0.38 vs. 1.32±0.25 vs. 1.65±0.39 mgldl, respectively; analysis of variance, P<0.01). Confounding factors of renal function such as age, body weight, cold and warm ischemic time, cytomegaly virus status, methylprednisone and cyclosporine dosages, cyclosporine concentrations, as well as concomitant antihypertensive medication did not differ among the three groups. In the long-term follow-up (5 years), combined endpoints were reached in 3 of 15 of the lower tertile group, in 3 of 15 of the median tertile group, and in 8 of 16 of the upper tertile group (log-rank test, P<0.01). No relation to long-term outcome was found when patients were stratified according to their CBP. Conclusion. In our small but homogenous study cohort 24-hr ABP was more closely related to renal function in patients after transplantation than CBP suggesting that 24-hr ABP is superior for evaluation of hypertension-related renal graft dysfunction.

Prospective analysis of the value of 24-hour ambulatory blood pressure on renal function after kidney transplantation.

Valaciclovir Reduces the Incidence of Cytomegalovirus Disease and Acute Graft Rejection in CMV-Seronegative Recipients of a Seropositive Cadaveric Renal Allograft

Hans H. Neumayer

Papers

Valacyclovir for the Prevention of Cytomegalovirus Disease after Renal Transplantation

Renal dysfunction as a risk factor for mortality and cardiovascular disease in renal transplantation: experience from the Assessment of Lescol in Renal Transplantation trial.

Prospective analysis of the value of 24-hour ambulatory blood pressure on renal function after kidney transplantation.

Valaciclovir Reduces the Incidence of Cytomegalovirus Disease and Acute Graft Rejection in CMV-Seronegative Recipients of a Seropositive Cadaveric Renal Allograft