RANDOMIZED CONTROLLED TRIAL OF STEROID WITHDRAWAL IN RENAL-TRANSPLANTRECIPIENTS RECEIVING TRIPLE IMMUNOSUPPRESSION

Background The combination of cyclosporin, azathioprine, and prednisol one (triple immunosuppression) is the most commonly used immunosuppres sive regimen early after renal transplantation, but the risks and bene fits of maintaining the steroid component of this regimen in the long term are uncertain. Methods A randomised controlled trial of steroid w ithdrawal was conducted among renal transplant patients receiving trip le immunosuppression. Between one and six years after transplantation, 100 such patients were randomised either to reduce prednisolone treat ment to zero over about four months or to maintain their triple immuno suppression unchanged. Outcome was analysed according to ''intention-t o-treat''. Findings In 42 (86%) of 49 patients allocated to steroid wi thdrawal, complete steroid withdrawal was achieved. Although these pat ients did not experience defined acute rejection episodes, insidious i ncreases in plasma creatinine were observed more frequently in this gr oup than in the controls. In 97 patients surviving one year after tria l entry, plasma creatinine exceeded the baseline by more than 25% at s ome time in the first year in 25 (53%) of 47 in the steroid withdrawal group compared with 9 (18%) of 50 in the control group (p<0.001, chi- square test). In some cases these increases were transient. However, w hen corrected for the baseline (entry) value significant differences b etween groups were apparent in both mean plasma creatinine and mean cr eatinine clearance; mean (SD) plasma creatinine values at entry, immed iately after withdrawal, and at one year were 138 (27), 151 (36), and 150 (36) mu mol/L in the steroid withdrawal group versus 138 (34), 140 (51), and 139 (47) mu mol/L in the control group (p=0.017, analysis o f covariance). Steroid withdrawal patients showed a further rise in me an plasma creatinine to 160 (44) and 161 (65) mu mol/L at two and thre e years from trial entry. Changes in several clinical and metabolic in dices were also observed in association with steroid withdrawal. Blood pressure declined but the reduction was incompletely sustained, being more evident immediately after steroid withdrawal than at one year. T otal cholesterol declined about 1 mmol/L in the steroid withdrawal gro up. Other changes associated with steroid withdrawal were reductions i n white cell count and haemoglobin and increases in plasma phosphate a nd alkaline phosphatase. Interpretation Late steroid withdrawal is fea sible in most patients with stable graft function on triple immunosupp ression and has potentially beneficial metabolic effects. However, a s ubstantial proportion of patients show a reduction in graft function, indicating a need for caution in considering the longterm outcome.