Long-Term Results With Cyclosporine Monotherapy in Renal Transplant Patients: A Multivariate Analysis of Risk Factors Giuseppe Montagnino, MD, Antonio Tarantino, MD, Massimo Maccario, MD, Attilio Elli, MD, Bruno Cesana, MD, and Claudio Ponticelli, MD ● There is little information on the long-term outcome of patients initially assigned to cyclosporine (CsA) monotherapy and requiring the addition of steroid therapy during follow-up. The aim of this report is to describe our experience with 143 first renal transplant recipients (120 cadaver transplants, 23 living donor transplants) random- ized to receive CsA monotherapy as a treatment arm of three consecutive controlled clinical trials. Median follow-up was 86 months. Thirty-four percent of the patients remained on the original CsA monotherapy, whereas the remaining 66% required the addition of steroid therapy. Cumulative patient and graft survivals at 11 years were 0.89 (95% confidence interval [CI], 0.83 to 0.95) and 0.62 (95% CI, 0.52 to 0.72), respectively. The 11-year graft survival for converted patients was 0.53 (95% CI, 0.39 to 0.67). Cumulative graft half-life was 19.9  3.47 (SE) years. According to the Cox model, variables at transplantation that correlated with a lower 11-year graft survival were yearly increases in age (relative risk [RR], 1.04; P  0.039), monthly increases in hemodialysis duration (RR, 1.01; P  0.029), no blood transfusion before transplantation (RR, 1.99; P  0.043), CsA administration in a double daily dose (RR, 2.35; P  0.008), and a cadaver donor transplant (RR, 4.76; P  0.039). Multivariate analysis of time-dependent variables showed that delayed graft function recovery (RR, 2.20; P  0.019) and the need to add steroid and/or azathioprine therapy (RR, 5.28; P  0.000) were also correlated with a lower graft survival. Patients who added steroid therapy developed infections (P F 0.001), cataracts (P F 0.001), cardiovascular complications (P  0.004), and arterial hypertension (P  0.024) more frequently than patients remaining on CsA monotherapy. Patients administered CsA in a single daily dose received significantly less CsA over the years (P  0.0042) than patients administered CsA in two divided doses. They also showed a trend toward greater creatinine clearance levels, although not statistically significant. In conclusion, this analysis showed that in patients assigned to CsA therapy alone, good long-term patient and graft survival probabilities can be obtained. In approximately one third of the patients, the use of steroids could be avoided for up to 11 years, and these patients had a better long-term outcome than those who required the addition of steroid therapy. Finally, in patients administered CsAin a single daily dose, the possibility of reducing CsA dosage probably led to better intrarenal hemodynamics with improving creatinine clearances.  2000 by the National Kidney Foundation, Inc. INDEX WORDS: Renal transplantation; cyclosporine (CsA) monotherapy; long-term evaluation; therapeutic conver- sion; multivariate analysis. A NUMBER OF controlled trials of renal transplant recipients 1-10 compared the ef- fects of monotherapy with cyclosporine (CsA) alone versus double therapy (DT) with CsA plus steroids or triple therapy (TT) with CsA plus steroids plus azathioprine. Although acute graft rejection was more frequent in patients assigned to receive CsA monotherapy, graft survival was not significantly different from that of patients administered DT or TT. However, little informa- tion is available about the follow-up of those patients assigned to monotherapy who required the addition of steroid therapy. 10 The aim of this study is to evaluate the factors that could influence the long-term course of first renal transplant recipients randomized to receive CsA-monotherapy immediately after transplanta- tion. We also separately evaluated the long-term outcome of patients who continued with mono- therapy and those who required the addition of steroid therapy to CsA to assess the impact of treatment change on patient and graft outcome. PATIENTS AND METHODS All patients who received a primary renal transplant in our unit since 1983 and who were assigned to CsA monotherapy were included in this analysis. One hundred forty-three first renal transplant recipients were analyzed; 120 patients re- ceived a graft from a cadaver donor and 23 patients from a living related donor. The follow-up of 128 patients enrolled on three previous prospective, randomized clinical trials 5,7,10 has been updated at 11 years. In more detail, 25 patients participated in a first single-center trial comparing CsA monotherapy with DT 5 ; 74 patients participated in a second single-center study comparing CsA monotherapy with TT 7 ; From the Divisione di Nefrologia e Dialisi and the Labo- ratorio Epidemiologico, Ospedale Maggiore IRCCS; Mi- lano, Italy. Received August 9, 1999; accepted in revised form Janu- ary 4, 2000. Address reprint requests to Giuseppe Montagnino, MD, Divisione di Nefrologia e Dialisi, Ospedale Maggiore IRCCS, Via Commenda 15, 20122, Milano, Italy. E-mail: monta@polic.cilea.it  2000 by the National Kidney Foundation, Inc. 0272-6386/00/3506-0017$3.00/0 doi:10.1053/ajkd.2000.7477 American Journal of Kidney Diseases, Vol 35, No 6 (June), 2000: pp 1135-1143 1135