Sirolimus and tacrolimus coefficient of variation is associated with rejection, donor-specific antibodies, and nonadherence.
Immunosuppression medication nonadherence has been associated with donor-specific antibodies and treatment-refractory rejection. Drug-level monitoring is a practical direct marker for nonadherence, as variations indicate erratic ingestion of medication. We previously reported that high variability in tacrolimus trough levels determined by the percent coefficient of variation (CV %) and standard deviation (SD) were associated with biopsy-proven rejection. We hypothesized that the CV % and SD in patients on a sirolimus/low-dose tacrolimus regimen may associate with self-reported medication nonadherence, rejection and donor-specific antibodies.



In this pilot feasibility study, we studied 37 biopsies in 23 pediatric renal transplant patients on both sirolimus and tacrolimus immunosuppression; CV %, SD, de novo donor-specific antibodies, rejection, and self-reported adherence were examined.



A cut-off sirolimus CV % of 25 maximized the percentage of biopsies correctly classified as rejection (32 of 37, or 86 %, p = 0.001). A cut-off tacrolimus CV % of 31 maximized the percentage of correctly classified biopsies (25 of 37, or 68 %, p = 0.09). Among patients with both high sirolimus and tacrolimus CV %, 67 % developed de novo donor-specific antibodies (p = 0.002) with a DQ predominance and 71 % reported nonadherence (p = 0.05).



In pediatric renal transplantation, sirolimus and tacrolimus CV % is a potential tool for monitoring patients at risk for allograft rejection and donor-specific antibodies secondary to medication nonadherence.
Division of Pediatric Nephrology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. helen.pizzo@cshs.org.
Helen P
HP
Pizzo
Division of Pediatric Nephrology, Mattel Children's Hospital UCLA, Los Angeles, CA, USA.
Robert B
RB
Ettenger
UCLA Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA.
David W
DW
Gjertson
UCLA Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA.
Elaine F
EF
Reed
UCLA Department of Pathology and Laboratory Medicine, Los Angeles, CA, USA.
Jennifer
J
Zhang
UCLA Department of Urology, Los Angeles, CA, USA.
H Albin
HA
Gritsch
Division of Pediatric Nephrology, Mattel Children's Hospital UCLA, Los Angeles, CA, USA.
Eileen W
EW
Tsai
D000906:Antibodies / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007668:Kidney / Q000276:immunology / Q000473:pathology; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D055118:Medication Adherence; D010865:Pilot Projects; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*; D014019:Tissue Donors; D016896:Treatment Outcome
D000906:Antibodies; D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus
Calcineurin inhibitor; Compliance; Drug levels; Immunosuppression; Mammalian target of rapamycin inhibitor