Control of cytomegalovirus disease in renal transplant patients treated with prednisone, azathioprine and cyclosporine using intensive monitoring anddecreased immunosuppression

Background: The aim of this trial was to study the effectiveness of intensi ve monitoring, together with an early decrease in immunosuppression, in red ucing 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, uns elected, renal transplant patients in our unit. Only 96 patients whose immu nosuppressive regimens consisted of prednisone, azathioprine and cyclospori ne and whose follow-up period was greater than 4 months were included in th e 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 withdr awn when the CMV-AG count was greater than 10 cells per 10(5) PBLs. The cyc losporine dose was gradually decreased in the next 4 weeks, but it was not withdrawn in any patient.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 posit ive 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 wit hdrawn 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 a nd 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 diseas e was of moderate intensity in both patients. Only 3/51 (5.8%) patients dev eloped acute rejection after the first CMV-AG detection in the 4 posttransp lant months. Conclusion: The results of this study suggest that intensive m onitoring and an early reduction of immunosuppression, together with preemp tive therapy in high-risk patients, is effective in diminishing the prevale nce and severity of CMV disease.