Chronic allograft dysfunction (CAD) is a major cause of graft loss in long-term kidney transplant recipients. To identify predictors of successful conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) we investigated 59 renal transplant patients with CAD without histological signs of acute rejection. They received 12-15 mg SRL once, then 4-5 mg/day, target trough level 8-12 ng/mL. CNI dose was reduced by 50% simultaneously, and withdrawn at 1-2 months. Concomitant immunosuppression remained unchanged. After 1 year patient survival was 100% and graft survival 92%. In responders (54%) creatinine improved (2.75 +/- 0.75 to 2.22 +/- 0.64 mg/dL; p < 0.01). In nonresponders (46%) creatinine deteriorated (3.15 +/- 1.02 to 4.44 +/- 1.60 mg/dL; p < 0.01). Baseline renal function did not differ, however, baseline proteinuria (519 +/- 516 vs. 1532 +/- 867 mg/day, p < 0.01), histological grade of chronic allograft nephropathy (CAN) (1.2 +/- 0.5 vs. 1.9 +/- 0.6; p < 0.01), grade of vascular fibrous intimal thickening (1.2 +/- 0.7 vs. 1.7 +/- 0.7; p = 0.048) and number of acute rejections before conversion (0.73 +/- 0.69 vs. 1.27 +/- 0.96; p < 0.05) differed significantly between responders and nonresponders. In a multivariate analysis low proteinuria was the only independent variable. Proteinuria below 800 mg/day has a positive predictive value of 90%. Proteinuria at conversion below 800 mg/day is the only independent predictor for positive outcome in conversion from CNI to SRL in CAD.