valganciclovir and Cadaver

During 10 years, 163 cadaveric kidney transplantations were performed at the Hospital of Kaunas University of Medicine. The aim of this study was to analyze the first 10-year experience in kidney transplantation and to evaluate the most frequent early and late complications after transplantation, graft and patient survival, and impact of delayed graft function on graft survival.. A total of 159 patients were included into the study. Graft and patient survival was calculated at 1, 3, and 5 years after transplantation using the Kaplan-Meier method; graft function was also analyzed.. Fifty-three patients (33.3%) in the early period and 72 (55.4%) in the late period had at least one episode of urinary tract infection. Less than half (47.2%) of patients had complications related to immunosuppressive treatment, mostly cytomegalovirus infection, in the late period. The risk of CMV reactivation was 3.98 times higher among recipients who received prophylaxis only with intravenous ganciclovir as compared to patients who received valganciclovir after a brief course of ganciclovir (OR, 3.98; 95% CI, 1.48-8.19; P=0.003). Delayed graft function was observed in 53 cases (33.3%); 37 (23.3%) grafts were lost. Graft and patient survival at 1, 3, and 5 years after transplantation was 85%, 82%, and 71% and 97%, 94%, and 94%, respectively. Graft survival at 1, 3, and 5 years was worse among patients with delayed graft function as compared to patients with good graft function (69%, 69%, 50% vs. 93%, 86%, 84%, respectively; P<0.05).. Urinary tract infection was the most frequent complication after kidney transplantation. Reactivation of cytomegalovirus infection was present only in a quarter of our patients. The administration of valganciclovir was associated with a significantly lower incidence of CMV infection/disease. Graft and patient survival was sufficiently good. Delayed graft function was an independent risk factor for worse graft survival.

Topics: Adolescent; Antiviral Agents; Cadaver; Chi-Square Distribution; Child; Cytomegalovirus Infections; Data Interpretation, Statistical; Female; Follow-Up Studies; Ganciclovir; Graft Survival; Hospitals, University; Humans; Immunosuppression Therapy; Kaplan-Meier Estimate; Kidney Diseases; Kidney Transplantation; Lithuania; Male; Patient Selection; Postoperative Complications; Renal Replacement Therapy; Statistics, Nonparametric; Survival Analysis; Time Factors; Urinary Tract Infections; Valganciclovir

Cytomegalovirus (CMV) infection and CMV disease remain important issues in renal transplantation. Incidence depends on individual patient risk. There are different possible strategies for CMV prophylaxis. In our center CMV prevention includes prophylaxis with low-dose valganciclovir for all high-risk recipients; for the remaining patients, valganciclovir is only prescribed when there is evidence of CMV replication. All recipients are monitored for viral replication. We evaluated the results of this preventive strategy in all 135 patients who underwent transplantation between 2006 and 2007 in our center. Average follow-up time was 16 months (6-30 months). Fifty-one recipients (38%) received CMV prophylaxis. The median duration of prophylaxis was 84 days. In 37% of the recipients (50 patients) CMV antigenemia became positive, and were given therapeutic doses of valganciclovir. Of these patients, 32% were high-risk recipients undergoing prophylaxis. CMV infection rate was 40% in the group not receiving prophylaxis. No association was observed between CMV infection and prophylaxis duration. However, 50% of patients who suspended prophylaxis before completion of the first 3 months became infected. There were 3 cases of CMV disease (2.2%). Leukopenia was seen in 34% of patients receiving prophylaxis. Valganciclovir prophylaxis for high-risk patients seems to be effective and safe among subjects who complete the full duration of treatment. Despite CMV-positive antigenemia in 40% of patients not undergoing prophylaxis, pre-emptive therapy with valganciclovir was effective to prevent CMV disease, but close monitoring is essential for disease prevention.

Topics: Antiviral Agents; Cadaver; Cytomegalovirus Infections; Ganciclovir; Humans; Kidney Transplantation; Living Donors; Postoperative Complications; Retrospective Studies; Tissue Donors; Valganciclovir

Valganciclovir is an l-valyl ester pro-drug of ganciclovir that was initially used to treat cytomegalovirus (CMV)-associated retinitis in patients with human immunodeficiency virus. Currently, it is also indicated for the prevention of CMV disease in solid-organ transplantation. It is primarily eliminated via the kidneys through glomerular filtration and tubular secretion. Decreased renal function results in decreased drug clearance. Valganciclovir has been reported to cause usually mild to moderate hematologic adverse effects such as leukopenia, neutropenia, anemia, thrombocytopenia, and pancytopenia. Severe and fatal bone marrow depression has been described in 1 adult patient. Herein, we describe the cases of 4 patients with end-stage renal disease who underwent cadaveric renal transplantation and received valganciclovir prophylaxis for CMV at a standard dose of 900 mg/d despite persistant renal failure. This therapy resulted in severe bone marrow failure after 18 to 20 days in all 4 patients, with fatal infections in 2 patients. This report demonstrates the in vivo pharmacodynamics of valganciclovir overdose in terms of hematotoxicity in the setting of renal impairment. Valganciclovir, as its derivative ganciclovir, should be used cautiously in patients with renal impairment.

Topics: Adult; Antilymphocyte Serum; Antiviral Agents; Biopsy; Bone Marrow; Cadaver; Female; Ganciclovir; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Middle Aged; T-Lymphocytes; Tissue Donors; Valganciclovir