Minimum mycophenolic acid levels are associated with donor-specific antibody formation

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 pos...

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Bibliographic Details
Published in:Pediatric transplantation 2016-02, Vol.20 (1), p.34-38
Main Authors: Filler, Guido, Todorova, Ekaterina Kirilova, Bax, Kevin, Alvarez-Elías, Ana Catalina, Huang, Shih-Han Susan, Kobrzynski, Marta Caroline
Format: Article
Language:English
Subjects:
Anthropometry
Antibodies - immunology
Antibody Formation
Area Under Curve
Child
Cohort Studies
Cystatin C - blood
donor-specific antibodies
Drug Monitoring
Female
Follow-Up Studies
Glomerular Filtration Rate
graft function
Graft Rejection - immunology
Graft Survival
Humans
Immunosuppressive Agents - therapeutic use
Kaplan-Meier Estimate
Kidney Transplantation
Male
mycophenolate mofetil
Mycophenolic Acid - blood
Mycophenolic Acid - therapeutic use
outcome
pediatric
Renal Insufficiency - blood
Renal Insufficiency - immunology
Renal Insufficiency - surgery
Tacrolimus - blood
Tacrolimus - therapeutic use
therapeutic drug monitoring
Tissue Donors
Transplant Recipients
Treatment Outcome
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Summary: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 m2) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m2, whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m2 (p = 0.0071). MPA trough levels
ISSN:1397-3142
1399-3046
DOI:10.1111/petr.12637