Rejection and function and chronic allograft dysfunction

Despite the impressive reduction in early acute rejection rates over the past decades, chronic allograft dysfunction remains a key issue after renal transplantation. A number of factors, such as the quality of the original organ, ischemia/reperfusion injury, and/or (treated) acute rejection, will adversely affect renal structure, causing early (but often mild) tubular atrophy and interstitial fibrosis. It remains, however, controversial whether subclinical acute rejection or borderline changes imply a different functional prognosis with longer times of follow-up, if cases with late clinical acute rejection, inadequate dosing, and/or incompliance with drug prescription are excluded. Serum creatinine and immunosuppressant trough levels constitute the current standard biomarkers for assessing and renal function and systemic drug exposure, respectively. Serum creatinine is a notoriously unreliable marker for the glomerular filtration rate; changes in creatinine concentration occur late in disease progression and do not accurately represent the ongoing underlying renal damage. Trough level monitoring without information on the patient's absorption profile or the related systemic drug exposure is equally unreliable for guiding initial calcineurin inhibitor dosing or for controlling systemic drug exposure while tapering. Until more sophisticated biomarkers to guide clinical immunosupprression become available, protocol biopsies may prove to be most useful in patients with an increased risk for (late) acute rejection.