Monitoring Nonadherence and Acute Rejection With Variation in Blood Immunosuppressant Levels in Pediatric Renal Transplantation

Abstract

BACKGROUND: Acute rejection associated with medication nonadherence is a major cause of allograft loss in pediatric kidney transplant patients. There is currently no reliable method to detect medication nonadherence and prevent allograft rejection. METHODS: In 46 pediatric patients who underwent renal transplantation between 2002 and 2003, the variation of serum drug levels was studied as a potential objective tool to monitor medication nonadherence. Tacrolimus (TAC) and mycophenolic acid (MPA) trough levels were measured from 1 to 12 months posttransplant, and standard deviation (SD) and percent coefficient of variation (CV%) were calculated. Because SD increased as mean trough levels rose, CV% (CV%=SD/mean multiplied by 100%) was used to eliminate this confounding effect. RESULTS: Ten of 46 patients had biopsy-proven rejection. The median TAC CV% was 53.4% in patients with biopsy-proven rejection, which was significantly higher than 30% in those without rejection (P=0.005). Median MPA CV% was 51.9% in patients without rejection and 45.1% in patients with rejection (P=NS). High TAC CV% correlated with increased risk for rejection, whereas MPA CV% did not. CONCLUSION: The TAC CV% seems to be a useful and superior marker, compared with SD alone, for assessing medication nonadherence and the possibility of allograft rejection in pediatric renal transplantation.