This commentary discusses the strengths and weaknesses of a recent study reported by Kobayashi and colleagues, in which paired serum samples from 297 renal transplant recipients who underwent transplantation between December 1972 and September 2004 were tested for the presence of human leukocyte antigen (HLA) antibody at two discrete time points following surgery (2004 and 2006). Urine samples collected on the same day as the serum samples, were also measured for urinary protein levels. The results of the study suggest that patients with a positive change in HLA antibody status in the post-transplantation period (i.e. from negative to positive) plus a positive urine protein test were at increased risk of developing graft dysfunction (i.e. increased serum creatinine level). Solely on the basis of these data, the authors advocate that patients should be monitored annually for de novo production of HLA antibodies and for an increased urinary protein level by use of simple and cost-effective approaches to assess the risk of graft dysfunction or failure. While the proposal is an intriguing one, this commentary identifies several issues and limitations regarding post-transplantation monitoring that should be considered.