The natural history of azathioprine compliance after renal transplantation

Successful renal transplantation requires long-term adherence to complex medical regimens, yet knowledge of post-transplant medication compliance is still inadequate.

The natural history of medication compliance was quantitatively documented using electronic medicine bottle monitors. Azathioprine use was recorded with medication monitors beginning at hospital discharge in a prospective cohort of 180 renal transplant recipients. These patients and 87 other eligible patients, declining study participation, were followed up to five years. Compliance rates were associated with discrete clinical outcomes: acute rejection, allograft loss, and death.

During the first six months, only 8% of all azathioprine doses were missed. However, individual compliance rates varied widely, ranging from 16 to 100%, and each month, on average, 18% of patients skipped medication for four or more days. Outcome events were not different between study participants and those refusing study. However, lower compliance rates during the first six months were associated in a "dose-response" fashion with acute rejection (P = 0.006) and allograft loss (P = 0.002). Declining compliance during the first 90 days was a strong risk factor both for later acute rejection (odds ratio = 13.9, 95% CI, 2.9 to 68, P = 0.001), and allograft loss (odds ratio = 4.3, 95% CI, 1.1 to 16, P = 0.032).

Electronic monitoring provides a temporal description and quantitation of medication compliance. Reduced azathioprine compliance was highly associated with acute rejection and allograft loss. Trends in early compliance behavior predict later outcomes, thus providing unique opportunities for intervention.