In 2015 we implemented surveillance donor-specific antibody (DSA) monitoring in our pediatric kidney transplant recipients (pKTR); we found that in stable pKTRs (i.e. no changes in T function), reduced-dose mycophenolate (MMF) was a risk factor for DSA formation (ATC 2016: Pub 251946). We subsequently optimized anti-proliferative (AP) immunosuppression (IS) targeting 900mg/m2/d MMF or 2mg/kg/d Azathioprine (Aza) and monitored DSAs. We collected baseline and follow-up data including: DSAs, type of IS [tacrolimus (TAC) vs. sirolimus (SIR)-based], AP agent dose, variation of 5 prior outpatient IS trough levels, proteinuria (PU) and estimated glomerular filtration rate (by Schwartz).

Initial and follow-up DSA testing was available in 59 stable pKTRs. Patients with unstable T function or biopsies with evidence of rejection were excluded.

Initial IS was thymoglobulin induction with steroids, TAC and MMF. Steroids were generally not withdrawn. TAC and MMF were either converted to SIR and Aza, respectively, for intolerance, or the MMF dose was reduced.

In clinically stable pKTRs, MMF and Aza doses were lower at initial DSA testing (629.3mg/m2/d and 1.1mg/kg/d, respectively) compared with follow-up (801mg/m2/d and 1.6mg/kg/d, p: 0.019 and 0.016 by T-test respectively). The number of KTRs with clinically significant class 1 DSAs (MFI > 2000) decreased from 8 to 6 after AP IS optimization (p <0.005, Chi squared); however, the number of KTRs with clinically significant class 2 DSAs (MFI > 2000) increased from 15 to 19 (p < 0.005, Chi-squared) after AP IS optimization. On initial DSA testing, DSA+ KTRs were on significantly less MMF (342.5 v 726.6 mg/m2/d, p: 0.002 by T-test); on follow-up DSA testing, there was no difference in MMF dosing between groups (768.6 v 832.0 mg/m2/d, p: 0.593). We found no significant differences in other examined parameters.

We conclude that suboptimal IS (especially AP) dosing is associated with DSA formation and that DSA (especially class 2) reduction by AP re-optimization is challenging in stable KTRs.

CITATION INFORMATION: Rounds A, Moss M, Bock M, Goebel J. Longitudinal Study of Donor Specific Antibodies in a Pediatric Kidney Transplant Population; Response to Optimization of Anti-Proliferative Therapy. Am J Transplant. 2017;17 (suppl 3).

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