Coefficient of Variation of Sirolimus and Tacrolimus Levels Is Associated With Acute Rejection, Donor Specific Antibodies, and Medication Nonadherence in Pediatric Renal Transplantation.

Abstract

Purpose: We previously reported that a high tacrolimus (TAC) % coefficient of variation (CV%) in pediatric (Ped) kidney transplant (KTx) patients (pts) is associated with acute rejection (Rej), development of donor specific antibodies (DSA) and medication nonadherence (MNA). We sought to determine the predictive value of the CV% of sirolimus (SLR) and/or TAC on KTx Rej, DSA and MNA in Ped KTx pts on SLR and TAC. Methods: Trough levels of SLR and TAC obtained within a 6 month period prior to a KTx biopsy (Bx) were used to determine CV% in 37 Bxs in 23 high risk pts, 2-18 years old, on SLR and low-dose TAC. Bxs were graded by 2009 Banff criteria. MNA by self-report defined as > 20% missed doses. DSA positivity defined as > 1000 MFI by Luminex assay. Results: High median SLR CV% of 40.8% was significantly associated with Rej (Fig.1, p=0.0001). A cut-off SLR CV% of 25% determined by ROC analysis predicted pts that would have Rej (Fig. 1, p=0.0001). Median TAC CV% was not associated with Rej (p=0.15). Patients with high SLR CV% were significantly more likely to show high TAC CV% (Fig.2, upper right quadrant, p<0.03). In this subgroup of high SLR and TAC CV%, 18 of 21 Bxs (86%) were associated with rejection (p=0.005), 11 of 16 (69%) developed DSA (p=0.03) and 15 of 21 (71%) reported MNA (p=0.05).Figure: No Caption available.Conclusion: Among pts on SLR and low-dose TAC immunosuppression, a high SLR CV% is a strong predictor of rejection. Pts with high SLR CV% are significantly more likely to have high TAC CV%. Pts with elevations in both SLR and TAC CV% are more likely to report MNA and develop rejection and DSA. Thus, in Ped KTx pts, SLR and TAC CV% can be an important tool to monitor rejection and DSA associated with MNA. DISCLOSURES:Ettenger, R.: Grant/Research Support, Novartis, Bristol Myers Squibb.