Volatility of Serum Creatinine Relative to Tacrolimus Levels Predicts Kidney Transplant Rejection

BACKGROUND: We hypothesized that greater volatility of creatinine (SCr) relative to tacrolimus levels [Tac] (VCT) is associated with an increased risk of rejection. MATERIAL AND METHODS: Retrospective chart review was performed of all single-kidney-only transplants in our Renal Transplant Program from March 2004 to March 2010 (n=117) whose immunosuppressive regimen included tacrolimus (n=81). We collected all available SCr and [Tac] over the first 2 years post-transplant and calculated the VCT for each patient. SCr and [Tac] values were excluded from the first month and from the rise that occurred immediately preceding a rejection episode. RESULTS: Univariate analysis revealed that VCT was associated with increased odds of biopsy-proven rejection. A logistic regression model including donor type and HLA matches revealed that VCT (OR=1.16 [1.07, 1.26], p=0.0004) was strongly associated with rejection. ROC curve analysis yielded an AUC=0.823 (p<0.0001). CONCLUSIONS: Increased volatility of SCr relative to [Tac] is associated with an increased risk of rejection. Whereas increased variation in [Tac] levels has been shown to indicate reduced adherence, increased VCT may signal 'immunologic unrest' in the graft. Further studies are warranted to determine if intervention at the time when volatility increases can lower the risk of an acute rejection episode.