As clinical transplantation and the care of transplant recipients have evolved, acute rejection is increasingly an unusual cause of graft loss. Instead, chronic rejection and death with function are currently responsible for the majority of losses. Presented elsewhere in this volume are data showing that the major risk factor for chronic rejection is an acute rejection episode.1 Within the patient group experiencing acute rejection, those with multiple rejection episodes or whose first rejection episode occurs late posttransplant are at increased risk for developing chronic rejection and late graft loss. Importantly, noncompliance with the immunosup-pressive regimen is associated with an increased risk for acute rejection (especially late acute rejection), chronic rejection, and graft loss.

The broadest definition of noncompliance is simply the failure of a patient to follow the advice of their healthcare providers. For the transplant patient compliance includes following complex advice, ranging from diet restrictions and weight goals, to regular attendance at laboratory and clinic visits. Conversely, whether behaviors are called compliance, adherence or persistency, each patient's active and effective participation in their own care is crucial to consistently successful outcomes.

Medication compliance focuses specifically on adhering to the dynamic multi-drug regimens routinely prescribed after transplantation. To better understand medication compliance in perspective, it is informative to consider the Physicians' Health Study.2 This study recruited over 33,000 male US physicians to prospectively examine the effect of aspirin on cardiovascular events. Of interest, among the 33,200 physician volunteers indicating a definite desire to participate, only 22,000 (66%) regularly took a single daily pill during the study's 18 week run-in period.3 Thus in spite of education, their obvious motivation and insight, faced with taking a chronic medication these physician volunteers fared no better than the majority of their own patients!

Significantly, post-transplant medication compliance is not a voluntary activity. Although the regimens are complex and the drugs themselves are of varying importance, overall medication noncompliance critically impacts transplant outcomes including acute rejection and graft loss.4

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