Long-Term Effects of Single Versus Double CsA Dosing in Kidney Transplantation A. Tarantino, G. Montagnino, B. Cesana, A. Aroldi, M. Campise, P. Passerini, and C. Ponticelli T HERE IS little information on the long-term outcome of patients initially assigned to cyclosporine (CsA) monotherapy. The aims of this report are to (1) describe our experience with renal transplant recipients who re- ceived CsA monotherapy early after transplantation, and (2) analyze the impact of CsA administration in single morning dose on the long-term follow-up. PATIENTS AND METHODS One hundred forty-three renal transplant recipients were treated with CsA alone from transplantation. Forty-nine patients remained on the original CsA monotherapy (group A), whereas the remain- ing 94 required the addition of steroids (group B). The reasons for conversion were acute rejection not responsive to high doses of intravenous steroids (75%), noncompliance with therapy (11%), CsA-related nephrotoxicity (7%), other undesired CsA-related side effects (5%), and neoplasia (2%). Multivariate analysis, ac- cording to Cox’s model, was used to identify the prognostic factors related to graft failure including death. Graft survival was calculated by the method proposed by Simon and Makuch. 1 This analysis requires primarily the choice of a clinically relevant starting time. We chose the median time of therapeutic conversion, in this case, equal to 38 days. Therefore, graft failure events occurring before this time were not considered. The graft survival probability of overall group was then estimated, treating the converted patients as censored observation at the time of their shifting. Both the survival curves for converted and for those remained in the original therapeutic protocol were obtained. RESULTS The median follow-up of 143 patients was 86 months. Twelve patients died, 5 of severe infection (in one associ- ated to neoplasia), 3 of acute myocardial infarction, 2 of neoplasia, 1 of cerebral hemorrhage, and 1 of hepatic failure. Thirty-five more patients lost their allografts be- cause of acute rejection (4 patients), chronic allograft nephropathy (24 patients), recurrence of original glomeru- lonephritis (2 patients), a combination of chronic dysfunc- tion and recurrent disease (2 patients), neoplasia of the graft (1 patient), graft rupture (1 patient), and ureteral fistula (1 patient). The cumulative patient and graft survivals at 11 years after transplantation were 0.89 and 0.62, respectively. The cumulative half-life was 19.9 years. The 11-year graft sur- vival in patients converted to dual or triple therapy was 0.53 (95% CI 0.39 to 0.67) significantly lower than that observed in patients never converted to other therapy (0.84, P = .002). At multivariate analysis, yearly increase in age (RR 1.04), dialysis duration more than 45 months (RR = 3.17), no transfusions prior transplantation (RR = 1.99), donor source (cadaver versus living) (RR = 4.76), and double versus single CsA dosing (RR = 2.35) were independently associated with a poor prognosis of graft survival. Seventy-one patients received CsA twice a day and 72 in a single morning dose. Patients on CsA single morning dose did not differ from patients given CsA in two divided doses as far as gender, number of rejections, or number of therapeutic shifts (all P = NS). Among the 72 patients who were given CsA single morning dose, 54 patients were treated continously with CsA in single morning dose from transplantation and 18 during the follow-up. The cumula- tive follow-up of these 72 patients was 121.7  55.2 months. The time spent on CsA single morning dose was 117.2  5.6 months. The 13-year patient and graft survival probability was 0.83 versus 0.86 and 0.55 versus 0.46, respectively. These differences were not significant, however. Fifty-eight patients were followed for 8 consecutive years; of them, 38 patients were administered CsA in a single morning dose and 20 patients in a divided dosage from the first days after transplantation. In the single morning group, the mean CsA dosage was significantly reduced over time (from 4.75  0.94 mg/kg/d at 6 months to 3.69  1.20 mg/kg/d at 8 years, P = .042) whereas the dosage remained stable in the divided-dosing group (4.66  0.76 mg/kg/d at 6 months versus 4.52  0.95 mg/kg/d at 8 years). The mean creatinine clearance, measured by Cockcroft and Gault formula, remained substantially stable in the divided-dose group (51.68  12 mL/min at 6 months and 51.70  17.9 mL/min at 8 years), whereas it tended to increase, although not significantly (P = .087) in the single-dosing group (from From the Dipartimento di Nefrologia, Urologia e Trapianto Renale (A.T., G.M., A.A., M.C., P.P., C.P.), and Laboratorio Epidemiologico, Ospedale Maggiore—IRCCS (B.C.), Milan, Italy. Address reprint requests to A. Tarantino, Dipartimento di Nefrologia, Urologia e Trapianto Renale, Via Francesco Sforza 35, 20122 Milan, Italy. © 2001 by Elsevier Science Inc. 0041-1345/01/$–see front matter 655 Avenue of the Americas, New York, NY 10010 PII S0041-1345(01)02469-1 Transplantation Proceedings, 33, 3409–3410 (2001) 3409