title: Minimum mycophenolic acid levels are associated with donor-specific antibody formation.
abstract: Although de novo DSA are associated with inferior graft survival, there are no effective strategies to prevent their formation. Underexposure to MPA (prodrug: MMF) also contributes to rejection rates early after transplantation, but the effect of this phenomenon on the formation of DSA long-term post-transplantation is unknown. Data are expressed as mean (standard deviation). All available data from 32 renal transplant recipients (age at transplantation 7.5 [4.5] yr) on tacrolimus and MPA immunosuppression with an average follow-up of 9.4 (s.d. 4.6) yr were analyzed. DSA were measured using the Luminex assay (>500 MFI was considered DSA-positive). Tacrolimus and MPA levels were measured with the Abbot Tacro II and EMIT assay, respectively. Among 1964 MPA and 3462 tacrolimus trough levels, the average MPA trough level was 3.2 (1.5) mg/L and the average tacrolimus level was 6.7 (2.8) ng/mL. At last follow-up, only 5/32 patients had undetectable DSA, with 5/32 having no class I antibodies and 6/32 having no class II antibodies. DSA formation was associated with a lower minimum MPA trough level (0.27 [0.23] vs. 0.47 [0.18] mg) and cystatin C eGFR (48 [21] vs. 70 [23] mL/min/1.73 m(2)) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m(2), whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m(2) (p = 0.0071). MPA trough levels <1.3 mg/L long-term post-transplantation are associated with the formation of DSA. The association between the formation of DSA and minimum MPA exposure may support a strategy for preventing the formation of DSA.
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada.|Department of Pathology and Laboratory Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.|Department of Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Guido
authors.initials: G
authors.lastname: Filler
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada.
authors.forename: Ekaterina Kirilova
authors.initials: EK
authors.lastname: Todorova
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Bax
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada.
authors.forename: Ana Catalina
authors.initials: AC
authors.lastname: Alvarez-Elías
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada.|Department of Medicine, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON, Canada.
authors.forename: Shih-Han Susan
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Schulich School of Medicine & Dentistry, London, ON, Canada.
authors.forename: Marta Caroline
authors.identifier: http://orcid.org/0000-0002-4568-1730
authors.initials: MC
authors.lastname: Kobrzynski
mesh_terms: D000886:Anthropometry; D000906:Antibodies / Q000276:immunology; D000917:Antibody Formation; D019540:Area Under Curve; D002648:Child; D015331:Cohort Studies; D055316:Cystatin C / Q000097:blood; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D009173:Mycophenolic Acid / Q000097:blood* / Q000627:therapeutic use*; D051437:Renal Insufficiency / Q000097:blood* / Q000276:immunology / Q000601:surgery*; D016559:Tacrolimus / Q000097:blood / Q000627:therapeutic use; D014019:Tissue Donors; D066027:Transplant Recipients; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D055316:Cystatin C; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D016559:Tacrolimus
keywords: donor-specific antibodies; graft function; kidney transplantation; mycophenolate mofetil; outcome; pediatric; therapeutic drug monitoring