Control of Cytomegalovirus Disease in Renal Transplant Patients Treated with Prednisone, Azathioprine and Cyclosporine Using Intensive Monitoring and Decreased Immunosuppression

Abstract

Background: The aim of this trial was to study the effectiveness of intensive monitoring, together with an early decrease in immunosuppression, in reducing the prevalence of CMV disease in renal transplant recipients treated with prednisone, azathioprine and cyclosporine. Methods: From 1/95 to 11/97 a prospective, longitudinal study was conducted among 146 consecutive, unselected, renal transplant patients in our unit. Only 96 patients whose immunosuppressive regimens consisted of prednisone, azathioprine and cyclosporine and whose follow-up period was greater than 4 months were included in the study. Preemptive therapy was administered to 27 high-risk patients. CMV antigenemia (CMV-AG) and other virological tests were performed weekly for the first 4 posttransplant months. The immunosuppression was decreased when the first positive CMV-AG was detected. Azathioprine was completely withdrawn when the CMV-AG count was greater than 10 cells per 10⁵ PBLs. The cyclosporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient. The prednisone dose was modified according to the immunosuppressive protocol. Results: 53% (51/96) of the patients had positive CMV-AG on at least one occasion. The dose of azathioprine was decreased after CMV-AG detection in 41/51 (80.4%) patients and it was completely withdrawn in 23 of these (45%). The mean decrease in the dose of azathioprine was 73 ± 31 (25–175) mg, a mean percentage decrease of 76 ± 27% (25–100%). The dose of cyclosporine was progressively decreased during the 4 weeks after detection of the first CMV-AG (mean cyclosporine levels: 210 ± 66, 196 ± 54 and 164 ± 36 ng/ml at the time of first CMV-AG detection, 2 and 4 weeks respectively, p < 0.0001, repeated measures analysis of variance). None of the 45 patients without CMV-AG and only 2 of 51 (3.9%) patients with CMV-AG developed symptomatic CMV disease (2% of the total). CMV disease was of moderate intensity in both patients. Only 3/51 (5.8%) patients developed acute rejection after the first CMV-AG detection in the 4 posttransplant months. Conclusion: The results of this study suggest that intensive monitoring and an early reduction of immunosuppression, together with preemptive therapy in high-risk patients, is effective in diminishing the prevalence and severity of CMV disease.

Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy

“…This finding is similar to the previous experience with CMV infection prior to the advent of Ganciclovir when reduction in immunosuppression was the mainstay of therapy [37]. One study has shown a significant reduction in CMV disease with preemptive reduction in immunosuppression [38].…”

“…Factors associated with high risk for graft loss and dysfunction in these patients include the severity of interstitial nephritis, chronic interstitial fibrosis, presence of crescents, late diagnosis and the use of polyclonal or monoclonal antibody therapy after diagnosis. Although reduction in immunosuppression leads to stabilization of renal function, no actual improvement in renal function has been reported [38]. Improvement in renal function in this series occurred in only 1 patient with ureteric stenosis.…”

Disseminated Herpes Simplex Type-2 (HSV-2) Infection After Solid-Organ Transplantation

“…HSV-2 isolates from both patients were similar to each other. Gomez et al [11] have reported on disseminated HSV-2 infection as a possible cause of repeated urinary extravasation. More recently, Nebbia et al [8] have reported a case of fatal primary HSV-2 infection following liver transplantation, which was transmitted by the graft, and manifested as fever and liver failure in the absence of muco-cutaneous disease.…”

Lymphocyte subpopulations during cytomegalovirus disease in renal transplant recipients

“…Our findings are consistent with previous studies showing that antigenemia is a suitable method for the diagnosis of active CMV infection and acts as an early marker for active CMV infection in most patients. No antigenemia-negative patient developed CMV disease over the 3-month study period (18,20), and of the 20 patients assumed to have CMV disease, 17 presented positive antigenemia prior to the appearance of clinical symptoms.…”