The only randomized study with protocol biopsies prior to randomization and strict confirmation of rejection by repeated biopsies was performed in the USA in 68 patients over a period of 2 years.All patients had a renal biopsy at trial initiation, and all clinical rejection episodes had to be confirmed by biopsy. Two important results were obtained: First, three patients unexpectedly
showed histological signs of rejection prior to study initiation,demonstrating how difficult the clinical identification of a stable patient can be.