Mycophenolic Acid Trough Concentration and Dose Are Associated with Hematologic Abnormalities but Not Rejection in Kidney Transplant Recipients.
BACKGROUND
Little is known regarding the safe fixed dose of mycophenolic acid (MPA) for preventing biopsy-proven acute rejection (BPAR) in kidney transplant recipients (KTRs). We investigated the correlation of MPA trough concentration (MPA C₀) and dose with renal transplant outcomes and adverse events.


METHODS
This study included 79 consecutive KTRs who received MPA with tacrolimus (TAC) and corticosteroids. The MPA C₀ of all the enrolled KTRs was measured, which was determined monthly by using particle-enhanced turbidimetric inhibition immunoassay for 12 months, and clinical data were collected at each time point. The clinical endpoints included BPAR, any cytopenia, and BK or cytomegalovirus infections.


RESULTS
No differences in MPA C₀ and dose were observed between KTRs with or without BPAR or viral infections under statistically comparable TAC concentrations. MPA C₀ was significantly higher in patients with leukopenia (P = 0.021) and anemia (P = 0.002) compared with those without cytopenia. The MPA dose was significantly higher in patients with thrombocytopenia (P = 0.002) compared with those without thrombocytopenia. MPA C₀ ≥ 3.5 μg/mL was an independent risk factor for leukopenia (adjusted odds ratio [AOR], 3.80; 95% confidence interval [CI], 1.24-11.64; P = 0.019) and anemia (AOR, 5.90; 95% CI, 1.27-27.51; P = 0.024). An MPA dose greater than the mean value of 1,188.8 mg/day was an independent risk factor for thrombocytopenia (AOR, 3.83; 95% CI, 1.15-12.78; P = 0.029). However, an MPA dose less than the mean value of 1,137.3 mg/day did not increase the risk of BPAR.


CONCLUSION
Either a higher MPA C₀ or dose is associated with an increased risk of cytopenia, but neither a lower MPA C₀ nor dose is associated with BPAR within the first year of transplantation. Hence, a reduced MPA dose with TAC and corticosteroids might be safe in terms of reducing hematologic abnormalities without causing rejection.
['Jung|Hee Yeon|HY|https://orcid.org/0000-0003-0232-7202', 'Lee|Sukyung|S|https://orcid.org/0000-0002-4727-1049', 'Jeon|Yena|Y|https://orcid.org/0000-0002-4857-8616', 'Choi|Ji Young|JY|https://orcid.org/0000-0002-9774-3665', 'Cho|Jang Hee|JH|https://orcid.org/0000-0002-7031-5214', 'Park|Sun Hee|SH|https://orcid.org/0000-0002-0953-3343', 'Kim|Yong Lim|YL|https://orcid.org/0000-0002-1344-3455', 'Kim|Hyung Kee|HK|https://orcid.org/0000-0002-4436-7424', 'Huh|Seung|S|https://orcid.org/0000-0002-0275-4960', 'Won|Dong Il|DI|https://orcid.org/0000-0002-1983-2515', 'Kim|Chan Duck|CD|https://orcid.org/0000-0002-4648-0324']
D000305:Adrenal Cortex Hormones D000328:Adult D000740:Anemia D004305:Dose-Response Relationship, Drug D004359:Drug Therapy, Combination D005260:Female D006084:Graft Rejection D006402:Hematologic Diseases D006801:Humans D007166:Immunosuppressive Agents D016030:Kidney Transplantation D007970:Leukopenia D016015:Logistic Models D008297:Male D008875:Middle Aged D009173:Mycophenolic Acid D016017:Odds Ratio D012307:Risk Factors D016559:Tacrolimus D013921:Thrombocytopenia
Mycophenolic Acid Dose Kidney Transplantation Drug Monitoring Graft Rejection